Medline ® Abstract for Reference 96
MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival.
Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M
J Gastrointest Surg. 2008 Dec;12(12):2171-6. Epub 2008 Jul 19.
BACKGROUND: MicroRNAs are small (18-22 nucleotides) noncoding RNAs involved in posttranscriptional modification of many target genes. One of these, microRNA-21 (miR-21), has been shown to play a role in multiple hematologic and solid organ malignancies. We sought to determine the expression pattern of miR-21 in pancreatic cancers and its impact on clinicopathologic characteristics.
METHODS: Eighty resected pancreatic cancer specimens were microdissected and tissue microarrays (TMA) created in duplicate. TMAs were also created for benign pancreas (N = 12) and chronic pancreatitis (N = 45). In situ hybridization (ISH) was undertaken utilizing locked nucleic acid probes for miR-21. RNA U6 and scrambled RNA served as positive and negative control, respectively. ISH was scored as 0 (absent), 1+ (faint/focal expression), or 2+ (strong expression). Kaplan-Meier survival curves were constructed and compared by log-rank analysis.
RESULTS: MiR-21 expression was demonstrated in 63 (79%) pancreatic cancers (1+ in 49, 2+ in 14) compared to one of 12 (8%, p<0.0001) benign pancreas and 12/45 (27%, p<0.0001) chronic pancreatitis. None of the benign tissues demonstrated strong miR-21 expression. Although miR-21 expression did not correlate with tumor size, differentiation, nodal status, or T stage, strong miR-21 expression was predictive of poorer outcome compared to absent or faint/focal miR-21 expression in patients with node-negative disease (median 27.7 months vs. 15.2, p = 0.037). Nodal status was also predictive of survival (p = 0.029).
CONCLUSIONS: MicroRNA-21 is significantly overexpressed in pancreatic cancers as detected by in situ hybridization. Its strong expression predicts limited survival in patients with node-negative disease and may be an important biologic marker for outcome.
Department of Surgery, The Ohio State University, 410 W. 10th Ave., N924 Doan Hall, Columbus, OH 43210, USA.