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Pathology and prognostic determinants of colorectal cancer

Carolyn C Compton, MD, PhD
Section Editor
Kenneth K Tanabe, MD
Deputy Editor
Diane MF Savarese, MD


Carcinoma of the colon or rectum (colorectal cancer [CRC]) is a common and lethal disease. Approximately 135,430 new cases are diagnosed each year in the United States, of which 95,520 are colon and the remainder rectal cancers [1]. Annually, approximately 50,260 Americans die of CRC, accounting for approximately 8 percent of all cancer deaths. Global, country-specific data on incidence and mortality are available from the World Health Organization (WHO) GLOBOCAN database.

Surgical resection is the primary treatment modality for early-stage CRC (stage I through III) (table 1), and the most powerful tool for assessing prognosis following potentially curative surgery is pathologic analysis of the resected specimen. Although the parameters that determine pathologic stage are the strongest predictors of postoperative outcome, other clinical, molecular, and histologic features may influence prognosis independent of stage. Among patients with stage IV disease, prognosis is more closely tied to the location and extent of distant metastatic disease.

Here we will discuss the pathology of CRC and the major determinants of prognosis following surgical resection, with particular attention to the strength of the evidence supporting each factor. The molecular pathogenesis of CRC and the clinical presentation and staging evaluation for colon and rectum cancer are discussed elsewhere. (See "Molecular genetics of colorectal cancer" and "Clinical presentation, diagnosis, and staging of colorectal cancer" and "Pretreatment local staging evaluation for rectal cancer".)


Gross appearance — Although all colorectal cancers (CRCs) originate in adenomas or flat dysplasia, they evolve into different morphologic patterns with invasion and expansion. Tumors in the proximal or right colon usually appear grossly as polypoid or fungating exophytic masses. Occult bleeding may result in the clinical presentation of an unexplained iron deficiency anemia.

By contrast, tumors involving the distal or left colon are more commonly annular or encircling lesions that produce an "apple-core" or "napkin-ring" appearance (image 1A-B). The bowel lumen becomes constricted and narrowed, producing symptoms of bowel dysfunction (eg, constipation, diarrhea, or bowel obstruction). The presence of clinical bowel obstruction or perforation of the bowel wall worsens the prognosis overall [2-4].

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Literature review current through: Nov 2017. | This topic last updated: Oct 20, 2017.
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  1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7.
  2. Carraro PG, Segala M, Cesana BM, Tiberio G. Obstructing colonic cancer: failure and survival patterns over a ten-year follow-up after one-stage curative surgery. Dis Colon Rectum 2001; 44:243.
  3. Griffin MR, Bergstralh EJ, Coffey RJ, et al. Predictors of survival after curative resection of carcinoma of the colon and rectum. Cancer 1987; 60:2318.
  4. Katoh H, Yamashita K, Wang G, et al. Prognostic significance of preoperative bowel obstruction in stage III colorectal cancer. Ann Surg Oncol 2011; 18:2432.
  5. Weiss JM, Pfau PR, O'Connor ES, et al. Mortality by stage for right- versus left-sided colon cancer: analysis of surveillance, epidemiology, and end results--Medicare data. J Clin Oncol 2011; 29:4401.
  6. Price TJ, Beeke C, Ullah S, et al. Does the primary site of colorectal cancer impact outcomes for patients with metastatic disease? Cancer 2015; 121:830.
  7. Loupakis F, Yang D, Yau L, et al. Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst 2015; 107.
  8. Langevin JM, Nivatvongs S. The true incidence of synchronous cancer of the large bowel. A prospective study. Am J Surg 1984; 147:330.
  9. Passman MA, Pommier RF, Vetto JT. Synchronous colon primaries have the same prognosis as solitary colon cancers. Dis Colon Rectum 1996; 39:329.
  10. Fante R, Roncucci L, Di GregorioC, et al. Frequency and clinical features of multiple tumors of the large bowel in the general population and in patients with hereditary colorectal carcinoma. Cancer 1996; 77:2013.
  11. Knox RD, Luey N, Sioson L, et al. Medullary colorectal carcinoma revisited: a clinical and pathological study of 102 cases. Ann Surg Oncol 2015; 22:2988.
  12. Compton CC, Fielding LP, Burgart LJ, et al. Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 2000; 124:979.
  13. AJCC (American Joint Committee on Cancer) Cancer Staging Manual, 7th edition, Edge, SB, Byrd, DR, Compton, CC, et al (Eds) (Eds), Springer, New York 2010. p.143.
  14. Green JB, Timmcke AE, Mitchell WT, et al. Mucinous carcinoma--just another colon cancer? Dis Colon Rectum 1993; 36:49.
  15. Secco GB, Fardelli R, Campora E, et al. Primary mucinous adenocarcinomas and signet-ring cell carcinomas of colon and rectum. Oncology 1994; 51:30.
  16. Minsky BD, Mies C, Rich TA, et al. Colloid carcinoma of the colon and rectum. Cancer 1987; 60:3103.
  17. Minsky BD. Clinicopathologic impact of colloid in colorectal carcinoma. Dis Colon Rectum 1990; 33:714.
  18. Consorti F, Lorenzotti A, Midiri G, Di Paola M. Prognostic significance of mucinous carcinoma of colon and rectum: a prospective case-control study. J Surg Oncol 2000; 73:70.
  19. Nitsche U, Zimmermann A, Späth C, et al. Mucinous and signet-ring cell colorectal cancers differ from classical adenocarcinomas in tumor biology and prognosis. Ann Surg 2013; 258:775.
  20. Shin US, Yu CS, Kim JH, et al. Mucinous rectal cancer: effectiveness of preoperative chemoradiotherapy and prognosis. Ann Surg Oncol 2011; 18:2232.
  21. Lee DW, Han SW, Lee HJ, et al. Prognostic implication of mucinous histology in colorectal cancer patients treated with adjuvant FOLFOX chemotherapy. Br J Cancer 2013; 108:1978.
  22. Hugen N, Verhoeven RH, Radema SA, et al. Prognosis and value of adjuvant chemotherapy in stage III mucinous colorectal carcinoma. Ann Oncol 2013; 24:2819.
  23. Nissan A, Guillem JG, Paty PB, et al. Signet-ring cell carcinoma of the colon and rectum: a matched control study. Dis Colon Rectum 1999; 42:1176.
  24. Psathakis D, Schiedeck TH, Krug F, et al. Ordinary colorectal adenocarcinoma vs. primary colorectal signet-ring cell carcinoma: study matched for age, gender, grade, and stage. Dis Colon Rectum 1999; 42:1618.
  25. Frizelle FA, Hobday KS, Batts KP, Nelson H. Adenosquamous and squamous carcinoma of the colon and upper rectum: a clinical and histopathologic study. Dis Colon Rectum 2001; 44:341.
  26. Masoomi H, Ziogas A, Lin BS, et al. Population-based evaluation of adenosquamous carcinoma of the colon and rectum. Dis Colon Rectum 2012; 55:509.
  27. Petrelli NJ, Valle AA, Weber TK, Rodriguez-Bigas M. Adenosquamous carcinoma of the colon and rectum. Dis Colon Rectum 1996; 39:1265.
  28. Jass JR, Sobin LH. Histological typing of intestinal tumours. In: WHO International Histological Classification of Tumours, 2nd, Springer-Verlag, Berlin-New York 1989.
  29. Ronnett BM, Kurman RJ, Shmookler BM, et al. The morphologic spectrum of ovarian metastases of appendiceal adenocarcinomas: a clinicopathologic and immunohistochemical analysis of tumors often misinterpreted as primary ovarian tumors or metastatic tumors from other gastrointestinal sites. Am J Surg Pathol 1997; 21:1144.
  30. AJCC (American Joint Committee on Cancer) Cancer Staging Manual, 7th ed, Edge, SB, Byrd, DR, Compton, CC, et al (Eds), Springer, New York 2010. p.133.
  31. Werling RW, Yaziji H, Bacchi CE, Gown AM. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol 2003; 27:303.
  32. Moll R, Zimbelmann R, Goldschmidt MD, et al. The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas. Differentiation 1993; 53:75.
  33. Landau MS, Kuan SF, Chiosea S, Pai RK. BRAF-mutated microsatellite stable colorectal carcinoma: an aggressive adenocarcinoma with reduced CDX2 and increased cytokeratin 7 immunohistochemical expression. Hum Pathol 2014; 45:1704.
  34. Guerrieri C, Frånlund B, Fristedt S, et al. Mucinous tumors of the vermiform appendix and ovary, and pseudomyxoma peritonei: histogenetic implications of cytokeratin 7 expression. Hum Pathol 1997; 28:1039.
  35. Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol 2000; 13:962.
  36. Hinoi T, Tani M, Lucas PC, et al. Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon. Am J Pathol 2001; 159:2239.
  37. McGregor DK, Wu TT, Rashid A, et al. Reduced expression of cytokeratin 20 in colorectal carcinomas with high levels of microsatellite instability. Am J Surg Pathol 2004; 28:712.
  38. Winn B, Tavares R, Fanion J, et al. Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation. Hum Pathol 2009; 40:398.
  39. Lin F, Shi J, Zhu S, et al. Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine. Arch Pathol Lab Med 2014; 138:1015.
  40. Weissman SM, Bellcross C, Bittner CC, et al. Genetic counseling considerations in the evaluation of families for Lynch syndrome--a review. J Genet Couns 2011; 20:5.
  41. Shia J. Immunohistochemistry versus microsatellite instability testing for screening colorectal cancer patients at risk for hereditary nonpolyposis colorectal cancer syndrome. Part I. The utility of immunohistochemistry. J Mol Diagn 2008; 10:293.
  42. Hampel H, Frankel WL, Martin E, et al. Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J Clin Oncol 2008; 26:5783.
  43. Jessup JM, Goldberg RM, Asare EA, et al.. Colon and Rectum. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed), AJCC, Chicago 2017. p.251.
  44. Sloothaak DA, Sahami S, van der Zaag-Loonen HJ, et al. The prognostic value of micrometastases and isolated tumour cells in histologically negative lymph nodes of patients with colorectal cancer: a systematic review and meta-analysis. Eur J Surg Oncol 2014; 40:263.
  45. Compton C, Fenoglio-Preiser CM, Pettigrew N, Fielding LP. American Joint Committee on Cancer Prognostic Factors Consensus Conference: Colorectal Working Group. Cancer 2000; 88:1739.
  46. Wiggers T, Arends JW, Volovics A. Regression analysis of prognostic factors in colorectal cancer after curative resections. Dis Colon Rectum 1988; 31:33.
  47. Chapuis PH, Dent OF, Fisher R, et al. A multivariate analysis of clinical and pathological variables in prognosis after resection of large bowel cancer. Br J Surg 1985; 72:698.
  48. Tominaga T, Sakabe T, Koyama Y, et al. Prognostic factors for patients with colon or rectal carcinoma treated with resection only. Five-year follow-up report. Cancer 1996; 78:403.
  49. Shepherd NA, Baxter KJ, Love SB. The prognostic importance of peritoneal involvement in colonic cancer: a prospective evaluation. Gastroenterology 1997; 112:1096.
  50. Zeng Z, Cohen AM, Hajdu S, et al. Serosal cytologic study to determine free mesothelial penetration of intraperitoneal colon cancer. Cancer 1992; 70:737.
  51. Panarelli NC, Schreiner AM, Brandt SM, et al. Histologic features and cytologic techniques that aid pathologic stage assessment of colonic adenocarcinoma. Am J Surg Pathol 2013; 37:1252.
  52. Washington MK, Berlin J, Branton PA, et al. Protocol for the examination of specimens from patients with primary carcinomas of the colon and rectum. Arch Pathol Lab Med 2008; 132:1182.
  53. http://www.cap.org/ShowProperty?nodePath=/UCMCon/Contribution Folders/WebContent/pdf/cp-colon-16protocol-3400.pdf (Accessed on January 12, 2017).
  54. Newland RC, Dent OF, Lyttle MN, et al. Pathologic determinants of survival associated with colorectal cancer with lymph node metastases. A multivariate analysis of 579 patients. Cancer 1994; 73:2076.
  55. Takahashi Y, Tucker SL, Kitadai Y, et al. Vessel counts and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer. Arch Surg 1997; 132:541.
  56. Michelassi F, Ayala JJ, Balestracci T, et al. Verification of a new clinicopathologic staging system for colorectal adenocarcinoma. Ann Surg 1991; 214:11.
  57. Kornprat P, Pollheimer MJ, Lindtner RA, et al. Value of tumor size as a prognostic variable in colorectal cancer: a critical reappraisal. Am J Clin Oncol 2011; 34:43.
  58. Willett CG, Goldberg S, Shellito PC, et al. Does postoperative irradiation play a role in the adjuvant therapy of stage T4 colon cancer? Cancer J Sci Am 1999; 5:242.
  59. Wittekind C, Compton CC, Greene FL, Sobin LH. TNM residual tumor classification revisited. Cancer 2002; 94:2511.
  60. Gress DM, Edge SB, Greene FL, et al.. Principles of Cancer Staging. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed), AJCC, Chicago 2017. p.29.
  61. Wittekind C, Compton C, Quirke P, et al. A uniform residual tumor (R) classification: integration of the R classification and the circumferential margin status. Cancer 2009; 115:3483.
  62. Nagtegaal ID, Quirke P. What is the role for the circumferential margin in the modern treatment of rectal cancer? J Clin Oncol 2008; 26:303.
  63. Adam IJ, Mohamdee MO, Martin IG, et al. Role of circumferential margin involvement in the local recurrence of rectal cancer. Lancet 1994; 344:707.
  64. Stocchi L, Nelson H, Sargent DJ, et al. Impact of surgical and pathologic variables in rectal cancer: a United States community and cooperative group report. J Clin Oncol 2001; 19:3895.
  65. Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision. Lancet 1986; 2:996.
  66. de Haas-Kock DF, Baeten CG, Jager JJ, et al. Prognostic significance of radial margins of clearance in rectal cancer. Br J Surg 1996; 83:781.
  67. Gosens MJ, Klaassen RA, Tan-Go I, et al. Circumferential margin involvement is the crucial prognostic factor after multimodality treatment in patients with locally advanced rectal carcinoma. Clin Cancer Res 2007; 13:6617.
  68. Parfitt JR, Driman DK. The total mesorectal excision specimen for rectal cancer: a review of its pathological assessment. J Clin Pathol 2007; 60:849.
  69. Nagtegaal ID, Marijnen CA, Kranenbarg EK, et al. Circumferential margin involvement is still an important predictor of local recurrence in rectal carcinoma: not one millimeter but two millimeters is the limit. Am J Surg Pathol 2002; 26:350.
  70. Bernstein TE, Endreseth BH, Romundstad P, et al. Circumferential resection margin as a prognostic factor in rectal cancer. Br J Surg 2009; 96:1348.
  71. Jessup JM, Goldberg RM, Aware EA, et al. Colon and Rectum. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed), AJCC, Chicago 2017. p.251.
  72. Yasuda K, Adachi Y, Shiraishi N, et al. Pattern of lymph node micrometastasis and prognosis of patients with colorectal cancer. Ann Surg Oncol 2001; 8:300.
  73. Clarke G, Ryan E, O'Keane JC, et al. The detection of cytokeratins in lymph nodes of Duke's B colorectal cancer subjects predicts a poor outcome. Eur J Gastroenterol Hepatol 2000; 12:549.
  74. Tschmelitsch J, Klimstra DS, Cohen AM. Lymph node micrometastases do not predict relapse in stage II colon cancer. Ann Surg Oncol 2000; 7:601.
  75. Markowitz SD. Cancer bypasses the lymph nodes. Science 2017; 357:35.
  76. Naxerova K, Reiter JG, Brachtel E, et al. Origins of lymphatic and distant metastases in human colorectal cancer. Science 2017; 357:55.
  77. Wolmark N, Fisher B, Wieand HS. The prognostic value of the modifications of the Dukes' C class of colorectal cancer. An analysis of the NSABP clinical trials. Ann Surg 1986; 203:115.
  78. Greene FL, Stewart AK, Norton HJ. A new TNM staging strategy for node-positive (stage III) colon cancer: an analysis of 50,042 patients. Ann Surg 2002; 236:416.
  79. Swanson RS, Compton CC, Stewart AK, Bland KI. The prognosis of T3N0 colon cancer is dependent on the number of lymph nodes examined. Ann Surg Oncol 2003; 10:65.
  80. Chen SL, Bilchik AJ. More extensive nodal dissection improves survival for stages I to III of colon cancer: a population-based study. Ann Surg 2006; 244:602.
  81. Tepper JE, O'Connell MJ, Niedzwiecki D, et al. Impact of number of nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol 2001; 19:157.
  82. Chang GJ, Rodriguez-Bigas MA, Skibber JM, Moyer VA. Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst 2007; 99:433.
  83. Johnson PM, Porter GA, Ricciardi R, Baxter NN. Increasing negative lymph node count is independently associated with improved long-term survival in stage IIIB and IIIC colon cancer. J Clin Oncol 2006; 24:3570.
  84. Le Voyer TE, Sigurdson ER, Hanlon AL, et al. Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. J Clin Oncol 2003; 21:2912.
  85. Compton CC. Optimal pathologic staging: defining stage II disease. Clin Cancer Res 2007; 13:6862s.
  86. Baxter NN, Ricciardi R, Simunovic M, et al. An evaluation of the relationship between lymph node number and staging in pT3 colon cancer using population-based data. Dis Colon Rectum 2010; 53:65.
  87. Berger AC, Sigurdson ER, LeVoyer T, et al. Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol 2005; 23:8706.
  88. Meyers MO, Hollis DR, Mayer RJ, et al. Ratio of metastatic to examined lymph nodes is a powerful predictor of overall survival in rectal cancer: An analysis of Intergroup 0114 (abstract). J Clin Oncol 2007; 25:165s.
  89. Ceelen W, Van Nieuwenhove Y, Pattyn P. Prognostic value of the lymph node ratio in stage III colorectal cancer: a systematic review. Ann Surg Oncol 2010; 17:2847.
  90. Moore J, Hyman N, Callas P, Littenberg B. Staging error does not explain the relationship between the number of lymph nodes in a colon cancer specimen and survival. Surgery 2010; 147:358.
  91. Parsons HM, Tuttle TM, Kuntz KM, et al. Association between lymph node evaluation for colon cancer and node positivity over the past 20 years. JAMA 2011; 306:1089.
  92. Wong SL, Ji H, Hollenbeck BK, et al. Hospital lymph node examination rates and survival after resection for colon cancer. JAMA 2007; 298:2149.
  93. Tsikitis VL, Larson DL, Wolff BG, et al. Survival in stage III colon cancer is independent of the total number of lymph nodes retrieved. J Am Coll Surg 2009; 208:42.
  94. Prandi M, Lionetto R, Bini A, et al. Prognostic evaluation of stage B colon cancer patients is improved by an adequate lymphadenectomy: results of a secondary analysis of a large scale adjuvant trial. Ann Surg 2002; 235:458.
  95. Bui L, Rempel E, Reeson D, Simunovic M. Lymph node counts, rates of positive lymph nodes, and patient survival for colon cancer surgery in Ontario, Canada: a population-based study. J Surg Oncol 2006; 93:439.
  96. National voluntary consensus standards for quality of cancer care from the National Quality Forum available online at www.qualityforum.org/pdf/cancer/txAppA-Specifications_web.pdf (Accessed on May 02, 2011).
  97. de Campos-Lobato LF, Stocchi L, de Sousa JB, et al. Less than 12 nodes in the surgical specimen after total mesorectal excision following neoadjuvant chemoradiation: it means more than you think! Ann Surg Oncol 2013; 20:3398.
  98. Baxter NN, Virnig DJ, Rothenberger DA, et al. Lymph node evaluation in colorectal cancer patients: a population-based study. J Natl Cancer Inst 2005; 97:219.
  99. Bilimoria KY, Bentrem DJ, Stewart AK, et al. Lymph node evaluation as a colon cancer quality measure: a national hospital report card. J Natl Cancer Inst 2008; 100:1310.
  100. Chang GJ, Taylor SH, Rodriguez-Bigas MA, Skibber JM, et al. The twelve lymph node standard in colon cancer: Can it be achieved? (abstract 448). Data presented at the 2008 ASCO GI Cancers Symposium, Orlando, FL, January 24, 2008.
  101. Morris EJ, Maughan NJ, Forman D, Quirke P. Identifying stage III colorectal cancer patients: the influence of the patient, surgeon, and pathologist. J Clin Oncol 2007; 25:2573.
  102. West NP, Hohenberger W, Weber K, et al. Complete mesocolic excision with central vascular ligation produces an oncologically superior specimen compared with standard surgery for carcinoma of the colon. J Clin Oncol 2010; 28:272.
  103. Abbassi-Ghadi N, Boshier PR, Goldin R, Hanna GB. Techniques to increase lymph node harvest from gastrointestinal cancer specimens: a systematic review and meta-analysis. Histopathology 2012; 61:531.
  104. Govindarajan A, Gönen M, Weiser MR, et al. Challenging the feasibility and clinical significance of current guidelines on lymph node examination in rectal cancer in the era of neoadjuvant therapy. J Clin Oncol 2011; 29:4568.
  105. Veronese N, Nottegar A, Pea A, et al. Prognostic impact and implications of extracapsular lymph node involvement in colorectal cancer: a systematic review with meta-analysis. Ann Oncol 2016; 27:42.
  106. Waldman S, Hyslop T, Schulz S, et al. A prospective multicenter study of guanyl cyclase C (GCC), quantified by the reverse transcriptase-polymerase chain reaction (qRT-PCR), as a prognostic marker of occult metastases in lymph nodes of pN0 colorectal cancer patients (abstract). J Clin Oncol 2008; 26:580s.
  107. Sargent DJ, Shi Q, Gill S, et al. Molecular testing for lymph node metastases as a determinant of colon cancer recurrence: results from a retrospective multicenter study. Clin Cancer Res 2014; 20:4361.
  108. Paramo JC, Summerall J, Wilson C, et al. Intraoperative sentinel lymph node mapping in patients with colon cancer. Am J Surg 2001; 182:40.
  109. Bernini A, Spencer M, Frizelle S, et al. Evidence for colorectal cancer micrometastases using reverse transcriptase-polymerase chain reaction analysis of MUC2 in lymph nodes. Cancer Detect Prev 2000; 24:72.
  110. Bilchik AJ, Nora DT, Sobin LH, et al. Effect of lymphatic mapping on the new tumor-node-metastasis classification for colorectal cancer. J Clin Oncol 2003; 21:668.
  111. Gill S, Haince JF, Shi Q, et al. Prognostic Value of Molecular Detection of Lymph Node Metastases After Curative Resection of Stage II Colon Cancer: A Systematic Pooled Data Analysis. Clin Colorectal Cancer 2015; 14:99.
  112. Rahbari NN, Bork U, Motschall E, et al. Molecular detection of tumor cells in regional lymph nodes is associated with disease recurrence and poor survival in node-negative colorectal cancer: a systematic review and meta-analysis. J Clin Oncol 2012; 30:60.
  113. Mescoli C, Albertoni L, Pucciarelli S, et al. Isolated tumor cells in regional lymph nodes as relapse predictors in stage I and II colorectal cancer. J Clin Oncol 2012; 30:965.
  114. Goldstein NS, Turner JR. Pericolonic tumor deposits in patients with T3N+MO colon adenocarcinomas: markers of reduced disease free survival and intra-abdominal metastases and their implications for TNM classification. Cancer 2000; 88:2228.
  115. Lo DS, Pollett A, Siu LL, et al. Prognostic significance of mesenteric tumor nodules in patients with stage III colorectal cancer. Cancer 2008; 112:50.
  116. Belt EJ, van Stijn MF, Bril H, et al. Lymph node negative colorectal cancers with isolated tumor deposits should be classified and treated as stage III. Ann Surg Oncol 2010; 17:3203.
  117. Nagtegaal ID, Knijn N, Hugen N, et al. Tumor Deposits in Colorectal Cancer: Improving the Value of Modern Staging-A Systematic Review and Meta-Analysis. J Clin Oncol 2017; 35:1119.
  118. Lord AC, D'Souza N, Pucher PH, et al. Significance of extranodal tumour deposits in colorectal cancer: A systematic review and meta-analysis. Eur J Cancer 2017; 82:92.
  119. Ruo L, Tickoo S, Klimstra DS, et al. Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapy. Ann Surg 2002; 236:75.
  120. Gavioli M, Luppi G, Losi L, et al. Incidence and clinical impact of sterilized disease and minimal residual disease after preoperative radiochemotherapy for rectal cancer. Dis Colon Rectum 2005; 48:1851.
  121. Ryan R, Gibbons D, Hyland JM, et al. Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology 2005; 47:141.
  122. Betge J, Pollheimer MJ, Lindtner RA, et al. Intramural and extramural vascular invasion in colorectal cancer: prognostic significance and quality of pathology reporting. Cancer 2012; 118:628.
  123. Hogan J, Chang KH, Duff G, et al. Lymphovascular invasion: a comprehensive appraisal in colon and rectal adenocarcinoma. Dis Colon Rectum 2015; 58:547.
  124. Quah HM, Chou JF, Gonen M, et al. Identification of patients with high-risk stage II colon cancer for adjuvant therapy. Dis Colon Rectum 2008; 51:503.
  125. Sternberg A, Sibirsky O, Cohen D, et al. Validation of a new classification system for curatively resected colorectal adenocarcinoma. Cancer 1999; 86:782.
  126. Takebayashi Y, Aklyama S, Yamada K, et al. Angiogenesis as an unfavorable prognostic factor in human colorectal carcinoma. Cancer 1996; 78:226.
  127. Santos C, López-Doriga A, Navarro M, et al. Clinicopathological risk factors of Stage II colon cancer: results of a prospective study. Colorectal Dis 2013; 15:414.
  128. Lim SB, Yu CS, Jang SJ, et al. Prognostic significance of lymphovascular invasion in sporadic colorectal cancer. Dis Colon Rectum 2010; 53:377.
  129. Amri R, England J, Bordeianou LG, Berger DL. Risk Stratification in Patients with Stage II Colon Cancer. Ann Surg Oncol 2016; 23:3907.
  130. Siddiqui MRS, Simillis C, Hunter C, et al. A meta-analysis comparing the risk of metastases in patients with rectal cancer and MRI-detected extramural vascular invasion (mrEMVI) vs mrEMVI-negative cases. Br J Cancer 2017; 116:1513.
  131. Benson AB 3rd, Schrag D, Somerfield MR, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 2004; 22:3408.
  132. Schmoll HJ, Van Cutsem E, Stein A, et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol 2012; 23:2479.
  133. Liebig C, Ayala G, Wilks J, et al. Perineural invasion is an independent predictor of outcome in colorectal cancer. J Clin Oncol 2009; 27:5131.
  134. Peng J, Sheng W, Huang D, et al. Perineural invasion in pT3N0 rectal cancer: the incidence and its prognostic effect. Cancer 2011; 117:1415.
  135. Huh JW, Kim HR, Kim YJ. Prognostic value of perineural invasion in patients with stage II colorectal cancer. Ann Surg Oncol 2010; 17:2066.
  136. Fujita S, Shimoda T, Yoshimura K, et al. Prospective evaluation of prognostic factors in patients with colorectal cancer undergoing curative resection. J Surg Oncol 2003; 84:127.
  137. Jessup JM, Goldberg RM, Asare EA, et al. Colon and Rectum. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed), AJCC, Chicago 2017. p.265.
  138. Cienfuegos JA, Martínez P, Baixauli J, et al. Perineural Invasion is a Major Prognostic and Predictive Factor of Response to Adjuvant Chemotherapy in Stage I-II Colon Cancer. Ann Surg Oncol 2017; 24:1077.
  139. Alotaibi AM, Lee JL, Kim J, et al. Prognostic and Oncologic Significance of Perineural Invasion in Sporadic Colorectal Cancer. Ann Surg Oncol 2017; 24:1626.
  140. Harrison JC, Dean PJ, el-Zeky F, Vander Zwaag R. From Dukes through Jass: pathological prognostic indicators in rectal cancer. Hum Pathol 1994; 25:498.
  141. Halvorsen TB, Seim E. Association between invasiveness, inflammatory reaction, desmoplasia and survival in colorectal cancer. J Clin Pathol 1989; 42:162.
  142. Ofner D, Riedmann B, Maier H, et al. Standardized staining and analysis of argyrophilic nucleolar organizer region associated proteins (AgNORs) in radically resected colorectal adenocarcinoma--correlation with tumour stage and long-term survival. J Pathol 1995; 175:441.
  143. Hyngstrom JR, Hu CY, Xing Y, et al. Clinicopathology and outcomes for mucinous and signet ring colorectal adenocarcinoma: analysis from the National Cancer Data Base. Ann Surg Oncol 2012; 19:2814.
  144. Hermanek P, Guggenmoos-Holzmann I, Gall FP. Prognostic factors in rectal carcinoma. A contribution to the further development of tumor classification. Dis Colon Rectum 1989; 32:593.
  145. Jessup JM, Stewart AK, Menck HR. The National Cancer Data Base report on patterns of care for adenocarcinoma of the rectum, 1985-95. Cancer 1998; 83:2408.
  146. Scott NA, Wieand HS, Moertel CG, et al. Colorectal cancer. Dukes' stage, tumor site, preoperative plasma CEA level, and patient prognosis related to tumor DNA ploidy pattern. Arch Surg 1987; 122:1375.
  147. Fisher ER, Sass R, Palekar A, et al. Dukes' classification revisited. Findings from the National Surgical Adjuvant Breast and Bowel Projects (Protocol R-01). Cancer 1989; 64:2354.
  148. Blenkinsopp WK, Stewart-Brown S, Blesovsky L, et al. Histopathology reporting in large bowel cancer. J Clin Pathol 1981; 34:509.
  149. Goldstein NS, Hart J. Histologic features associated with lymph node metastasis in stage T1 and superficial T2 rectal adenocarcinomas in abdominoperineal resection specimens. Identifying a subset of patients for whom treatment with adjuvant therapy or completion abdominoperineal resection should be considered after local excision. Am J Clin Pathol 1999; 111:51.
  150. Hamilton SR, Bosman FT, Boffetta P, et al.. Carcinoma of the colon and rectum. In: WHO Classification of Tumours of the Digestive System, 4th ed, Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds), International Agency for Research on Cancer, Lyon 2010. p.134.
  151. Tarantino I, Hüttner FJ, Warschkow R, et al. Prognostic Relevance of Mucinous Subtype in a Population-based Propensity Score Analysis of 40,083 Rectal Cancer Patients. Ann Surg Oncol 2016; 23:1576.
  152. Hugen N, van de Velde CJ, Bosch SL, et al. Modern Treatment of Rectal Cancer Closes the Gap Between Common Adenocarcinoma and Mucinous Carcinoma. Ann Surg Oncol 2015; 22:2669.
  153. Kim SH, Shin SJ, Lee KY, et al. Prognostic value of mucinous histology depends on microsatellite instability status in patients with stage III colon cancer treated with adjuvant FOLFOX chemotherapy: a retrospective cohort study. Ann Surg Oncol 2013; 20:3407.
  154. Shepherd NA, Saraga EP, Love SB, Jass JR. Prognostic factors in colonic cancer. Histopathology 1989; 14:613.
  155. Morikawa T, Kuchiba A, Qian ZR, et al. Prognostic significance and molecular associations of tumor growth pattern in colorectal cancer. Ann Surg Oncol 2012; 19:1944.
  156. Hase K, Shatney C, Johnson D, et al. Prognostic value of tumor "budding" in patients with colorectal cancer. Dis Colon Rectum 1993; 36:627.
  157. Minsky BD, Mies C, Rich TA, Recht A. Lymphatic vessel invasion is an independent prognostic factor for survival in colorectal cancer. Int J Radiat Oncol Biol Phys 1989; 17:311.
  158. Rogers AC, Winter DC, Heeney A, et al. Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer. Br J Cancer 2016; 115:831.
  159. van Wyk HC, Park J, Roxburgh C, et al. The role of tumour budding in predicting survival in patients with primary operable colorectal cancer: a systematic review. Cancer Treat Rev 2015; 41:151.
  160. Koelzer VH, Zlobec I, Berger MD, et al. Tumor budding in colorectal cancer revisited: results of a multicenter interobserver study. Virchows Arch 2015; 466:485.
  161. Canna K, McArdle PA, McMillan DC, et al. The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer. Br J Cancer 2005; 92:651.
  162. Pagès F, Berger A, Camus M, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 2005; 353:2654.
  163. Naito Y, Saito K, Shiiba K, et al. CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 1998; 58:3491.
  164. Prall F, Dührkop T, Weirich V, et al. Prognostic role of CD8+ tumor-infiltrating lymphocytes in stage III colorectal cancer with and without microsatellite instability. Hum Pathol 2004; 35:808.
  165. Pagès F, Kirilovsky A, Mlecnik B, et al. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol 2009; 27:5944.
  166. Lee WS, Park S, Lee WY, et al. Clinical impact of tumor-infiltrating lymphocytes for survival in stage II colon cancer. Cancer 2010; 116:5188.
  167. Mlecnik B, Tosolini M, Kirilovsky A, et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 2011; 29:610.
  168. Huh JW, Lee JH, Kim HR. Prognostic significance of tumor-infiltrating lymphocytes for patients with colorectal cancer. Arch Surg 2012; 147:366.
  169. Galon J, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313:1960.
  170. Rozek LS, Schmit SL, Greenson JK, et al. Tumor-Infiltrating Lymphocytes, Crohn's-Like Lymphoid Reaction, and Survival From Colorectal Cancer. J Natl Cancer Inst 2016; 108.
  171. Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 2006; 6:295.
  172. Salama P, Phillips M, Grieu F, et al. Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol 2009; 27:186.
  173. Jenkins MA, Hayashi S, O'Shea AM, et al. Pathology features in Bethesda guidelines predict colorectal cancer microsatellite instability: a population-based study. Gastroenterology 2007; 133:48.
  174. Greenson JK, Huang SC, Herron C, et al. Pathologic predictors of microsatellite instability in colorectal cancer. Am J Surg Pathol 2009; 33:126.
  175. Ogino S, Nosho K, Irahara N, et al. Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype. Clin Cancer Res 2009; 15:6412.
  176. Väyrynen JP, Sajanti SA, Klintrup K, et al. Characteristics and significance of colorectal cancer associated lymphoid reaction. Int J Cancer 2014; 134:2126.
  177. Harrison JC, Dean PJ, el-Zeky F, Vander Zwaag R. Impact of the Crohn's-like lymphoid reaction on staging of right-sided colon cancer: results of multivariate analysis. Hum Pathol 1995; 26:31.
  178. Nosho K, Baba Y, Tanaka N, et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. J Pathol 2010; 222:350.
  179. Jass JR, Do KA, Simms LA, et al. Morphology of sporadic colorectal cancer with DNA replication errors. Gut 1998; 42:673.
  180. Messerini L, Vitelli F, De Vitis LR, et al. Microsatellite instability in sporadic mucinous colorectal carcinomas: relationship to clinico-pathological variables. J Pathol 1997; 182:380.
  181. Rüschoff J, Dietmaier W, Lüttges J, et al. Poorly differentiated colonic adenocarcinoma, medullary type: clinical, phenotypic, and molecular characteristics. Am J Pathol 1997; 150:1815.
  182. Kim H, Jen J, Vogelstein B, Hamilton SR. Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol 1994; 145:148.
  183. Lanza G, Gafà R, Santini A, et al. Immunohistochemical test for MLH1 and MSH2 expression predicts clinical outcome in stage II and III colorectal cancer patients. J Clin Oncol 2006; 24:2359.
  184. Angelova M, Charoentong P, Hackl H, et al. Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy. Genome Biol 2015; 16:64.
  185. Galon J, Mlecnik B, Bindea G, et al. Towards the introduction of the 'Immunoscore' in the classification of malignant tumours. J Pathol 2014; 232:199.
  186. Sis B, Sarioglu S, Sokmen S, et al. Desmoplasia measured by computer assisted image analysis: an independent prognostic marker in colorectal carcinoma. J Clin Pathol 2005; 58:32.
  187. Crispino P, De Toma G, Ciardi A, et al. Role of desmoplasia in recurrence of stage II colorectal cancer within five years after surgery and therapeutic implication. Cancer Invest 2008; 26:419.
  188. Roncucci L, Fante R, Losi L, et al. Survival for colon and rectal cancer in a population-based cancer registry. Eur J Cancer 1996; 32A:295.
  189. Deans GT, Heatley M, Anderson N, et al. Jass' classification revisited. J Am Coll Surg 1994; 179:11.
  190. Caporale A, Amore Bonapasta S, Scarpini M, et al. Quantitative investigation of desmoplasia as a prognostic indicator in colorectal cancer. J Invest Surg 2010; 23:105.
  191. Des Guetz G, Uzzan B, Nicolas P, et al. Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer 2006; 94:1823.
  192. Foley EF, Gaffey MJ, Frierson HF Jr. The frequency and clinical significance of neuroendocrine cells within stage III adenocarcinomas of the colon. Arch Pathol Lab Med 1998; 122:912.
  193. Liu Y, Xu J, Jiao Y, et al. Neuroendocrine differentiation is a prognostic factor for stage II poorly differentiated colorectal cancer. Biomed Res Int 2014; 2014:789575.
  194. Cho YB, Yang SS, Lee WY, et al. The clinical significance of neuroendocrine differentiation in T3-T4 node-negative colorectal cancer. Int J Surg Pathol 2010; 18:201.
  195. Gaffey MJ, Mills SE, Lack EE. Neuroendocrine carcinoma of the colon and rectum. A clinicopathologic, ultrastructural, and immunohistochemical study of 24 cases. Am J Surg Pathol 1990; 14:1010.
  196. de Bruïne AP, Wiggers T, Beek C, et al. Endocrine cells in colorectal adenocarcinomas: incidence, hormone profile and prognostic relevance. Int J Cancer 1993; 54:765.
  197. Grabowski P, Schindler I, Anagnostopoulos I, et al. Neuroendocrine differentiation is a relevant prognostic factor in stage III-IV colorectal cancer. Eur J Gastroenterol Hepatol 2001; 13:405.
  198. Karim S, Brennan K, Nanji S, et al. Association Between Prognosis and Tumor Laterality in Early-Stage Colon Cancer. JAMA Oncol 2017; 3:1386.
  199. Zhang Y, Ma J, Zhang S, et al. A prognostic analysis of 895 cases of stage III colon cancer in different colon subsites. Int J Colorectal Dis 2015; 30:1173.
  200. Holch JW, Ricard I, Stintzing S, et al. The relevance of primary tumour location in patients with metastatic colorectal cancer: A meta-analysis of first-line clinical trials. Eur J Cancer 2017; 70:87.
  201. Petrelli F, Tomasello G, Borgonovo K, et al. Prognostic Survival Associated With Left-Sided vs Right-Sided Colon Cancer: A Systematic Review and Meta-analysis. JAMA Oncol 2016; 3:211.
  202. O'Dwyer PJ, Manola J, Valone FH, et al. Fluorouracil modulation in colorectal cancer: lack of improvement with N -phosphonoacetyl- l -aspartic acid or oral leucovorin or interferon, but enhanced therapeutic index with weekly 24-hour infusion schedule--an Eastern Cooperative Oncology Group/Cancer and Leukemia Group B Study. J Clin Oncol 2001; 19:2413.
  203. Tejpar S, Stintzing S, Ciardiello F, et al. Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. JAMA Oncol 2016.
  204. Sinicrope FA, Mahoney MR, Yoon HH, et al. Analysis of Molecular Markers by Anatomic Tumor Site in Stage III Colon Carcinomas from Adjuvant Chemotherapy Trial NCCTG N0147 (Alliance). Clin Cancer Res 2015; 21:5294.
  205. Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012; 487:330.
  206. Wolmark N, Fisher B, Wieand HS, et al. The prognostic significance of preoperative carcinoembryonic antigen levels in colorectal cancer. Results from NSABP (National Surgical Adjuvant Breast and Bowel Project) clinical trials. Ann Surg 1984; 199:375.
  207. Park YJ, Park KJ, Park JG, et al. Prognostic factors in 2230 Korean colorectal cancer patients: analysis of consecutively operated cases. World J Surg 1999; 23:721.
  208. Meling GI, Rognum TO, Clausen OP, et al. Serum carcinoembryonic antigen in relation to survival, DNA ploidy pattern, and recurrent disease in 406 colorectal carcinoma patients. Scand J Gastroenterol 1992; 27:1061.
  209. Lindmark G, Bergström R, Påhlman L, Glimelius B. The association of preoperative serum tumour markers with Dukes' stage and survival in colorectal cancer. Br J Cancer 1995; 71:1090.
  210. Harrison LE, Guillem JG, Paty P, Cohen AM. Preoperative carcinoembryonic antigen predicts outcomes in node-negative colon cancer patients: a multivariate analysis of 572 patients. J Am Coll Surg 1997; 185:55.
  211. Park IJ, Choi GS, Lim KH, et al. Serum carcinoembryonic antigen monitoring after curative resection for colorectal cancer: clinical significance of the preoperative level. Ann Surg Oncol 2009; 16:3087.
  212. Thirunavukarasu P, Sukumar S, Sathaiah M, et al. C-stage in colon cancer: implications of carcinoembryonic antigen biomarker in staging, prognosis, and management. J Natl Cancer Inst 2011; 103:689.
  213. Thirunavukarasu P, Talati C, Munjal S, et al. Effect of Incorporation of Pretreatment Serum Carcinoembryonic Antigen Levels Into AJCC Staging for Colon Cancer on 5-Year Survival. JAMA Surg 2015; 150:747.
  214. Kim CG, Ahn JB, Jung M, et al. Preoperative Serum Carcinoembryonic Antigen Level as a Prognostic Factor for Recurrence and Survival After Curative Resection Followed by Adjuvant Chemotherapy in Stage III Colon Cancer. Ann Surg Oncol 2017; 24:227.
  215. Locker GY, Hamilton S, Harris J, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol 2006; 24:5313.
  216. Liu ZH, Li C, Huang NQ, et al. No difference of complete or incomplete left-sided malignant colonic obstruction on both short- and long-term outcomes. Genet Mol Res 2014; 13:7965.
  217. Niedzwiecki D, Bertagnolli MM, Warren RS, et al. Documenting the natural history of patients with resected stage II adenocarcinoma of the colon after random assignment to adjuvant treatment with edrecolomab or observation: results from CALGB 9581. J Clin Oncol 2011; 29:3146.
  218. Faivre-Finn C, Bouvier-Benhamiche AM, Phelip JM, et al. Colon cancer in France: evidence for improvement in management and survival. Gut 2002; 51:60.
  219. Chen HS, Sheen-Chen SM. Obstruction and perforation in colorectal adenocarcinoma: an analysis of prognosis and current trends. Surgery 2000; 127:370.
  220. Mohd Suan MA, Tan WL, Soelar SA, et al. Intestinal obstruction: predictor of poor prognosis in colorectal carcinoma? Epidemiol Health 2015; 37:e2015017.
  221. Tougeron D, Sickersen G, Mouillet G, et al. Predictors of disease-free survival in colorectal cancer with microsatellite instability: An AGEO multicentre study. Eur J Cancer 2015; 51:925.
  222. Hong KD, Um JW, Ji WB, et al. Endoscopic obstruction in rectal cancers: survival and recurrence patterns following curative surgery. J Laparoendosc Adv Surg Tech A 2015; 25:278.
  223. Hatano S, Ishida H, Ishibashi K, et al. Identification of risk factors for recurrence in high-risk stage II colon cancer. Int Surg 2013; 98:114.
  224. Koebrugge B, Vogelaar FJ, Lips DJ, et al. The number of high-risk factors is related to outcome in stage II colonic cancer patients. Eur J Surg Oncol 2011; 37:964.
  225. Ho YH, Siu SK, Buttner P, et al. The effect of obstruction and perforation on colorectal cancer disease-free survival. World J Surg 2010; 34:1091.
  226. Petersen VC, Baxter KJ, Love SB, Shepherd NA. Identification of objective pathological prognostic determinants and models of prognosis in Dukes' B colon cancer. Gut 2002; 51:65.
  227. Belt EJ, Stockmann HB, Abis GS, et al. Peri-operative bowel perforation in early stage colon cancer is associated with an adverse oncological outcome. J Gastrointest Surg 2012; 16:2260.
  228. Honoré C, Goéré D, Souadka A, et al. Definition of patients presenting a high risk of developing peritoneal carcinomatosis after curative surgery for colorectal cancer: a systematic review. Ann Surg Oncol 2013; 20:183.
  229. Saha AK, Smith KJ, Sue-Ling H, et al. Prognostic factors for survival after curative resection of Dukes' B colonic cancer. Colorectal Dis 2011; 13:1390.
  230. Banaszkiewicz Z, Woda Ł, Tojek K, et al. Colorectal cancer with intestinal perforation - a retrospective analysis of treatment outcomes. Contemp Oncol (Pozn) 2014; 18:414.
  231. Ghazi S, Berg E, Lindblom A, et al. Clinicopathological analysis of colorectal cancer: a comparison between emergency and elective surgical cases. World J Surg Oncol 2013; 11:133.
  232. Sepulveda AR, Hamilton SR, Allegra CJ, et al. Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and the American Society of Clinical Oncology. J Clin Oncol 2017; 35:1453.
  233. Rowland A, Dias MM, Wiese MD, et al. Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer. Br J Cancer 2015; 112:1888.
  234. Pietrantonio F, Petrelli F, Coinu A, et al. Predictive role of BRAF mutations in patients with advanced colorectal cancer receiving cetuximab and panitumumab: a meta-analysis. Eur J Cancer 2015; 51:587.
  235. Shibata D, Peinado MA, Ionov Y, et al. Genomic instability in repeated sequences is an early somatic event in colorectal tumorigenesis that persists after transformation. Nat Genet 1994; 6:273.
  236. Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science 1993; 260:816.
  237. Lothe RA, Peltomäki P, Meling GI, et al. Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res 1993; 53:5849.
  238. Gryfe R, Kim H, Hsieh ET, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 2000; 342:69.
  239. Sankila R, Aaltonen LA, Järvinen HJ, Mecklin JP. Better survival rates in patients with MLH1-associated hereditary colorectal cancer. Gastroenterology 1996; 110:682.
  240. Watanabe T, Wu TT, Catalano PJ, et al. Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med 2001; 344:1196.
  241. Kohonen-Corish MR, Daniel JJ, Chan C, et al. Low microsatellite instability is associated with poor prognosis in stage C colon cancer. J Clin Oncol 2005; 23:2318.
  242. Malesci A, Laghi L, Bianchi P, et al. Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer. Clin Cancer Res 2007; 13:3831.
  243. Hutchins G, Southward K, Handley K, et al. Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol 2011; 29:1261.
  244. Sinicrope FA, Mahoney MR, Smyrk TC, et al. Prognostic impact of deficient DNA mismatch repair in patients with stage III colon cancer from a randomized trial of FOLFOX-based adjuvant chemotherapy. J Clin Oncol 2013; 31:3664.
  245. Smith CG, Fisher D, Claes B, et al. Somatic profiling of the epidermal growth factor receptor pathway in tumors from patients with advanced colorectal cancer treated with chemotherapy ± cetuximab. Clin Cancer Res 2013; 19:4104.
  246. Venderbosch S, Nagtegaal ID, Maughan TS, et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res 2014; 20:5322.
  247. Gonsalves WI, Mahoney MR, Sargent DJ, et al. Patient and tumor characteristics and BRAF and KRAS mutations in colon cancer, NCCTG/Alliance N0147. J Natl Cancer Inst 2014; 106.
  248. Cerottini JP, Caplin S, Saraga E, et al. The type of K-ras mutation determines prognosis in colorectal cancer. Am J Surg 1998; 175:198.
  249. Andreyev HJ, Norman AR, Cunningham D, et al. Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study. J Natl Cancer Inst 1998; 90:675.
  250. Samowitz WS, Curtin K, Schaffer D, et al. Relationship of Ki-ras mutations in colon cancers to tumor location, stage, and survival: a population-based study. Cancer Epidemiol Biomarkers Prev 2000; 9:1193.
  251. Yoon HH, Tougeron D, Shi Q, et al. KRAS codon 12 and 13 mutations in relation to disease-free survival in BRAF-wild-type stage III colon cancers from an adjuvant chemotherapy trial (N0147 alliance). Clin Cancer Res 2014; 20:3033.
  252. Modest DP, Ricard I, Heinemann V, et al. Outcome according to KRAS-, NRAS- and BRAF-mutation as well as KRAS mutation variants: pooled analysis of five randomized trials in metastatic colorectal cancer by the AIO colorectal cancer study group. Ann Oncol 2016; 27:1746.
  253. Taieb J, Zaanan A, Le Malicot K, et al. Prognostic Effect of BRAF and KRAS Mutations in Patients With Stage III Colon Cancer Treated With Leucovorin, Fluorouracil, and Oxaliplatin With or Without Cetuximab: A Post Hoc Analysis of the PETACC-8 Trial. JAMA Oncol 2016; :1.
  254. Taieb J, Le Malicot K, Shi Q, et al. Prognostic Value of BRAF and KRAS Mutations in MSI and MSS Stage III Colon Cancer. J Natl Cancer Inst 2017; 109.
  255. Clarke GA, Ryan E, Crowe JP, et al. Tumour-derived mutated K-ras codon 12 expression in regional lymph nodes of stage II colorectal cancer patients is not associated with increased risk of cancer-related death. Int J Colorectal Dis 2001; 16:108.
  256. Troungos C, Valavanis C, Kapranos N, Kittas C. K-ras mutation in Greek patients with poorly and moderately differenciated tumours of the lower intestinal tract. Anticancer Res 1997; 17:1399.
  257. Esteller M, González S, Risques RA, et al. K-ras and p16 aberrations confer poor prognosis in human colorectal cancer. J Clin Oncol 2001; 19:299.
  258. Andreyev HJ, Norman AR, Cunningham D, et al. Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study. Br J Cancer 2001; 85:692.
  259. Cercek A, Braghiroli MI, Chou JF, et al. Clinical Features and Outcomes of Patients with Colorectal Cancers Harboring NRAS Mutations. Clin Cancer Res 2017; 23:4753.
  260. Roth AD, Tejpar S, Delorenzi M, et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol 2010; 28:466.
  261. Gavin PG, Colangelo LH, Fumagalli D, et al. Mutation profiling and microsatellite instability in stage II and III colon cancer: an assessment of their prognostic and oxaliplatin predictive value. Clin Cancer Res 2012; 18:6531.
  262. Popovici VC, Budinska E, Roth A, et al. BRAF and KRAS mutations as additional risk factors in the context of clinical parameters of patients with colorectal cancer (abstract). J Clin Oncol 31, 2013 (suppl; abstr 3522). BRAF and KRhttp://meetinglibrary.asco.org/content/111853-132 (Accessed on June 18, 2013).
  263. Samowitz WS, Sweeney C, Herrick J, et al. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers. Cancer Res 2005; 65:6063.
  264. Yokota T, Ura T, Shibata N, et al. BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer. Br J Cancer 2011; 104:856.
  265. Seppälä TT, Böhm JP, Friman M, et al. Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer. Br J Cancer 2015; 112:1966.
  266. Jones JC, Renfro LA, Al-Shamsi HO, et al. Non-V600 BRAF Mutations Define a Clinically Distinct Molecular Subtype of Metastatic Colorectal Cancer. J Clin Oncol 2017; :JCO2016714394.
  267. Munro AJ, Lain S, Lane DP. P53 abnormalities and outcomes in colorectal cancer: a systematic review. Br J Cancer 2005; 92:434.
  268. McShane LM, Altman DG, Sauerbrei W, et al. Reporting recommendations for tumor marker prognostic studies (REMARK). J Natl Cancer Inst 2005; 97:1180.
  269. Yamanaka T, Oki E, Yamazaki K, et al. 12-Gene Recurrence Score Assay Stratifies the Recurrence Risk in Stage II/III Colon Cancer With Surgery Alone: The SUNRISE Study. J Clin Oncol 2016; 34:2906.
  270. Noffsinger AE. Serrated polyps and colorectal cancer: new pathway to malignancy. Annu Rev Pathol 2009; 4:343.
  271. Guinney J, Dienstmann R, Wang X, et al. The consensus molecular subtypes of colorectal cancer. Nat Med 2015; 21:1350.
  272. Sadanandam A, Lyssiotis CA, Homicsko K, et al. A colorectal cancer classification system that associates cellular phenotype and responses to therapy. Nat Med 2013; 19:619.
  273. De Sousa E Melo F, Wang X, Jansen M, et al. Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions. Nat Med 2013; 19:614.
  274. Marisa L, de Reyniès A, Duval A, et al. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value. PLoS Med 2013; 10:e1001453.
  275. Phipps AI, Limburg PJ, Baron JA, et al. Association between molecular subtypes of colorectal cancer and patient survival. Gastroenterology 2015; 148:77.
  276. Becht E, de Reyniès A, Giraldo NA, et al. Immune and Stromal Classification of Colorectal Cancer Is Associated with Molecular Subtypes and Relevant for Precision Immunotherapy. Clin Cancer Res 2016; 22:4057.
  277. Calon A, Lonardo E, Berenguer-Llergo A, et al. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet 2015; 47:320.
  278. Isella C, Terrasi A, Bellomo SE, et al. Stromal contribution to the colorectal cancer transcriptome. Nat Genet 2015; 47:312.
  279. Dienstmann R, Vermeulen L, Guinney J, et al. Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer. Nat Rev Cancer 2017; 17:79.
  280. Ubink I, Elias SG, Moelans CB, et al. A Novel Diagnostic Tool for Selecting Patients With Mesenchymal-Type Colon Cancer Reveals Intratumor Subtype Heterogeneity. J Natl Cancer Inst 2017; 109.
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