UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Medline ® Abstracts for References 5-9

of 'Molecular pathogenesis of exocrine pancreatic cancer'

5
TI
Treatment of familial pancreatic cancer and its precursors.
AU
Hruban RH, Canto MI, Griffin C, Kern SE, Klein AP, Laheru D, Yeo CJ
SO
Curr Treat Options Gastroenterol. 2005;8(5):365.
 
Approximately 10% of pancreatic cancers are believed to have a familial basis. The familial aggregation of pancreatic cancers provides a unique opportunity to prevent the development of pancreatic cancer, to identify and treat precancerous lesions of the pancreas, and to advance our understanding of the genetic basis for the development of all forms of pancreatic cancer. After appropriate genetic counseling, individuals with a strong family history of pancreatic cancer can now be tested for inherited genetic alterations that are known to increase the risk of pancreatic cancer. These include germline BRCA2, STK11/LKB1, p16/CDKN2A and PRSS1 gene mutations. Individuals with one of these inherited genetic alterations and individuals with a strong family history of pancreatic cancer can be counseled on smoking cessation and possible dietary modifications. Selected individuals, even if they are asymptomatic, can be screened using a combination of endoscopic ultrasound and multidetector computed tomography. Patients found to have a mass lesion in the pancreas would then be candidates for surgical resection. The resection of noninvasive precancers will cure these lesions before they have the opportunity to spread and metastasize. Even with the best early detection efforts, some patients will still be diagnosed with an invasive cancer. Surgical resection of invasive pancreatic cancer is proven to be safe and can provide long-term survival in patients with small, node-negative, and margin-negative cancers. Chemotherapy and radiation therapy are effective in some patients with invasive pancreatic cancer, but these therapies do not usually result in long-term cures. Individuals with a family history of pancreatic cancer may also choose to join a research study such as the National Familial Pancreas Tumor Registry.
AD
The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, 401 North Broadway, Weinberg 2249, Baltimore, MD 21231, USA. rhruban@jhmi.edu
PMID
6
TI
Molecular characterization of pancreatic neoplasms.
AU
Shi C, Daniels JA, Hruban RH
SO
Adv Anat Pathol. 2008;15(4):185.
 
Molecular analyses of neoplasms of the pancreas, coupled with careful histopathologic examination has helped refine the classification of pancreatic neoplasia. A number of molecularly and histologically distinct subtypes of pancreatic neoplasms have been identified and, importantly, many of these subtypes have important clinical implications. For example, most of the solid-pseudopapillary neoplasms harbor mutations in the beta-catenin gene (CTNNB1), and, as a result, most solid-pseudopapillary neoplasms have an abnormal nuclear pattern of labeling with antibodies to the beta-catenin protein. Clinically, patients with a solid-pseudopapillary neoplasm have a much better prognosis than do patients with ductal adenocarcinoma of the pancreas. Therefore, the immunolabeling of a pancreatic biopsy for the beta-catenin protein can help identify patients with low-risk neoplasms. It is clear that the time is now ripe for a new modern classification of neoplasms of the pancreas; a classification that does not abandon gross and microscopic pathology, but which instead integrates molecular findings with gross, microscopic, and clinical findings.
AD
Departments of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
PMID
7
TI
Progression model for pancreatic cancer.
AU
Hruban RH, Goggins M, Parsons J, Kern SE
SO
Clin Cancer Res. 2000;6(8):2969.
 
AD
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. rhruban@jhmi.edu
PMID
8
TI
Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression.
AU
Wilentz RE, Iacobuzio-Donahue CA, Argani P, McCarthy DM, Parsons JL, Yeo CJ, Kern SE, Hruban RH
SO
Cancer Res. 2000;60(7):2002.
 
Infiltrating adenocarcinomas of the pancreas are believed to arise from histologically identifiable intraductal precursors [pancreatic intraepithelial neoplasias (PanINs)]that undergo a series of architectural, cytological, and genetic changes. The role of DPC4 tumor suppressor gene inactivation in this progression has not been defined. Immunohistochemistry for the Dpc4 protein in formalin-fixed, paraffin-embedded tissue is a sensitive and specific marker for DPC4 gene status, providing a tool to examine DPC4 status in these putative precursor lesions. A total of 188 PanINs were identified in 40 pancreata, 38 (95%) of which also contained an infiltrating adenocarcinoma. Sections containing these 188 duct lesions were labeled with a monoclonal antibody to Dpc4. All 82 flat (PanIN-1A), all 54 papillary (PanIN-1B), and all 23 atypical papillary (PanIN-2) intraductal lesions expressed Dpc4. In contrast, 9 of 29 (31%) severely atypical lesions (PanIN-3 lesions, carcinomas in situ) did not. The difference in Dpc4 expression between histologically low-grade (PanIN-1 and -2) and histologically high-grade (PanIN-3) duct lesions was statistically significant (P<0.0001). In three cases, the pattern of Dpc4 expression in the PanIN-3 lesions did not match the pattern of expression in the associated infiltrating carcinomas, indicating that these high-grade lesions did not simply represent infiltrating carcinoma growing along benign ducts. Loss of Dpc4 expression occurs biologically late in the neoplastic progression that leads to the development of infiltrating pancreatic cancer, at the stage of histologically recognizable carcinoma.
AD
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
PMID
9
TI
A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas.
AU
Basturk O, Hong SM, Wood LD, Adsay NV, Albores-Saavedra J, Biankin AV, Brosens LA, Fukushima N, Goggins M, Hruban RH, Kato Y, Klimstra DS, Klöppel G, Krasinskas A, Longnecker DS, Matthaei H, Offerhaus GJ, Shimizu M, Takaori K, Terris B, Yachida S, Esposito I, Furukawa T, Baltimore Consensus Meeting
SO
Am J Surg Pathol. 2015;39(12):1730.
 
International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reportingprecursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other lesions. Consensus recommendations include the following: (1) To improve concordance and to align with practical consequences, a 2-tiered system (low vs. high grade) is proposed for all precursor lesions, with the provision that the current PanIN-2 and neoplasms with intermediate-grade dysplasia now be categorized as low grade. Thus, "high-grade dysplasia" is to be reserved for only the uppermost end of the spectrum ("carcinoma in situ"-type lesions). (2) Current data indicate that PanIN of any grade at a margin of a resected pancreas with invasive carcinoma does not have prognostic implications; the clinical significance of dysplasia at a margin in a resected pancreas with IPMN lacking invasive carcinoma remains to be determined. (3) Intraductal lesions 0.5 to 1 cm can be either large PanINs or small IPMNs. The term "incipient IPMN" should be reserved for lesions in this size with intestinal or oncocytic papillae or GNAS mutations. (4) Measurement of the distance between an IPMN and invasive carcinoma and sampling of intervening tissue are recommended to assess concomitant versus associated status. Conceptually, concomitant invasive carcinoma (in contrast with the "associated" group) ought to be genetically distinct from an IPMN elsewhere in the gland. (5) "Intraductal spread of invasive carcinoma" (aka, "colonization") is recommended to describe lesions of invasive carcinoma invading back into and extending along the ductal system, which may morphologically mimic high-grade PanIN or even IPMN. (6) "Simple mucinous cyst" is recommended to describe cysts>1 cm having gastric-type flat mucinous lining at most minimal atypia without ovarian-type stroma to distinguish them from IPMN. (7) Human lesions resembling the acinar to ductal metaplasia and atypical flat lesions of genetically engineered mouse models exist andmay reflect an alternate pathway of carcinogenesis; however, their biological significance requires further study. These revised recommendations are expected to improve our management and understanding of precursor lesions in the pancreas.
AD
*Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY‡Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD§Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA§§Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH†Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Ulsan, Korea∥Department of Pathology, Medica Sur Clinic and Foundation, Mexico City, Mexico¶Wolfson Wohl Cancer Research Centre, University of Glasgow, Glasgow, UK #Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands **Department of Pathology, Jichi Medical University, Shimotsuke††Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research¶¶Department of Pathology, Hakujikai Memorial Hospital†††Division of Cancer Genomics, National Cancer Center Research Institute§§§
PMID