BACKGROUND: Maspin (a tumor suppressor gene) is down-regulated in breast, prostate, gastric, and melanoma. Although it is not detected in normal pancreatic tissue, it is over-expressed in pancreatic cancer suggesting that maspin may play different activities in different cell types. Pancreatic ductal adenocarcinoma (PC) acquires maspin expression through hypomethylation of its promoter. AIM: Because the discrimination between ampullary and periampullary carcinomas is challenging in advanced cases, this inspired us to search for the use of maspin expression to discriminate between ampullary carcinoma (AC), PC, duodenal adenocarcinoma (DC), and other confusing benign and inflammatory pancreatic lesions. METHODS: Immunostaining for maspin was performed for 80 pancreaticoduodenal lesions. Sixty cases were malignant: 48 cases of pancreatic epithelial tumor (41 PC and 7 solid pseudopapillary neoplasm), 9 AC, and 3 DC. Twenty cases were non-malignant: 12 inflammatory (chronic pancreatitis), 5 benign neoplastic (serous cystadenomas), and 3 normal pancreatic tissue. Cytoplasmic and/or nuclear staining was considered positive as: Focally positive (5–50% of tumor cells), diffusely positive (>50% of tumor cells), or negative (<5% tumor cells). RESULTS: Maspin expression (positive/negative), distribution (focal/diffuse), and nuclear expression are significantly different between PC, solid pseudopapillary neoplasm, AC, and DC. PC shows significantly higher expression with more diffuse positivity and more nuclear expression than other malignant groups. Forty cases of PC (40/41) (97.6%) showed positive expression; 28 of them (28/40) (70%) showed diffuse expression and 82.5% (33 cases) showed nuclear and cytoplasmic expression. Only one case (14.3%) (1/7) of solid pseudopapillary neoplasm showed positive focal cytoplasmic expression. Three AC cases (3/9) (33.3%) showed positive focal cytoplasmic expression. Two cases of DC (2/3) (66.7%) showed positive focal cytoplasmic expression. Maspin expression shows significant positive correlation with poor prognostic variables as tumor grade, lymphovascular invasion, T stage of PC. Minority of chronic pancreatitis and benign lesions are maspin positive with significant difference from the malignant groups. CONCLUSION: Our results suggest that maspin can be of value in differentiating pancreatic adenocarcinoma from ampullary carcinoma, duodenal adenocarcinoma, and other confusing lesions as chronic pancreatitis.

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