AIM: To compare the clinicopathological features of pancreatic intraepithelial
neoplasias (PanINs) and intraductal papillary
mucinous neoplasms (IPMNs), and to investigate the role of hsa-miR-96 and
hsa-miR-217 in these two lesions. Methods:
Formalin-fixed
paraffin-embedded pancreatic specimens were selected in this study, including 58 cases of pancreatic intraepithelial
neoplasias (PanINs), 45 cases of pancreatic ductal
adenocarcinomas (PDAs), and 57 cases of intraductal papillary
mucinous neoplasms (IPMNs).
MiRNAs hsa-miR-96 and
hsa-miR-217 were detected using
locked nucleic acid in situ hybridization (LNA-ISH) with the NBT/BCIP staining system. The differences in
miRNA expression among sample sets were analyzed with the Chi-squared test. Results: PanIN-PDAs were inclined to present with higher rate of invasion (p=0.033),
lymph node metastasis (p=0.0004) and poorer differentiation (p<0.001). Of the 45 PDAs, only 2 cases were within AJCC Ⅰstage, while there were 11 cases of IPMN associated
carcinomas (p=0.0018). In PanIN-1, PanIN-2 and PanIN-3, the expression of hsa-miR-96 was 91.3% (22/23), 78.6%(12/17) and 22.2%(4/18) respectively, while the expression of
hsa-miR-217 was 95.7%(22/23) , 70.6% (12/17) and 27.8% (5/18). In IPMN with low-grade, intermediate-grade, high-grade dysplasia, associated
carcinoma, the expression of hsa-miR-96 was 67%(9/13), 64%(7/11), 43%(3/7) and 27%(7/26) respectively, while the expression of
hsa-miR-217 was 77%(10/13), 64%(7/11), 29%(2/7) and 38%(10/26). The expression of hsa-miR-96 and
hsa-miR-217 in PanIN-1 lesions was not significantly different from that in the normal pancreatic ductal epithelium. However, their expression in PanIN-2/3 lesions was significantly different from that in normal pancreatic ductal epithelium (P<0.01). No difference was observed between PanIN derived
adenocarcinomas and IPMN-associated
carcinomas. Conclusion: IPMN associated
carcinomas were in a statistically earlier stage than PanIN- PDAs at the time of operation. Abnormal expression of hsa-miR-96 and of
hsa-miR-217 was observed in premalignant lesions (PanINs and IPMNs) of
pancreatic carcinoma and down-regulated with increasing grades of PanINs and IPMNs. These
microRNAs may serve as potentially early
biomarker and act as tumor suppressor genes.