Stromal Fibrosis and Expression of Matricellular Proteins Correlate With Histological Grade of Intraductal Papillary Mucinous Neoplasm of the Pancreas

Objective: The aim of the study was to clarify the correlation between the microenvironmental factors and histological grade in intraductal papillary mucinous neoplasm (IPMN). Methods: We investigated 65 IPMNs resected at Yamagata University Hospital between 2000 and 2011, and all cases were categorized to low-inter (including low- and intermediate-grade dysplasia) and high-inv (including high-grade dysplasia and IPMN with an associated invasive carcinoma) groups. We compared between the 2 groups pathologically with regard to fibrosis and the expression of alpha-smooth muscle actin (alpha-SMA), periostin, and galectin-1 in the periductal stroma of IPMN. Results: There were 41 low-inter and 24 high-inv. The subtype was categorized as 22 main duct type (MD-IPMN) and 43 branch duct type (BD-IPMN). The degree of fibrosis and the expression of alpha-SMA, periostin, and galectin-1 were significantly higher in high-inv than in low-inter within BD-IPMNs. Multivariate logistic regression analysis indicated that high expression of alpha-SMA (odds ratio, 13.802; 95% confidence interval, 1.108-171.893; P = 0.0414) was a significant independent related factor of high-inv in BD-IPMN. Conclusions: Stromal fibrosis and expression of a-SMA, periostin, and galectin-1 are more marked in high-inv than in low-inter within BD-IPMNs, and they could become new markers for determining the indications for surgery in BD-IPMN.