Immunohistochemical analysis and in situ hybridization of cyclooxygenase‐2 expression in intraductal papillary‐mucinous tumors of the pancreas

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Abstract
BACKGROUND The objective of this study was to investigate COX‐2 expression in intraductal papillary‐mucinous tumor of the pancreas (IPMT) using immunohistochemical staining (IH) and in situ hybridization (ISH). METHODS Immunohistochemical staining of COX‐2 was performed using samples from 42 patients with IPMT (hyperplasia, 10; adenoma, 13; noninvasive adenocarcinoma, 13; invasive adenocarcinoma, 6) and from 10 patients with ductal pancreatic adenocarcinoma, 10 with chronic pancreatitis, and 6 normal pancreatic tissues as controls. Also, COX‐2 was determined in five patients with IPMT noninvasive adenocarcinoma, in whom all histologic types, hyperplasia, adenoma, and adenocarcinoma were observed in the same excised specimens. Furthermore, IH of proliferating cell nuclear antigen (PCNA) was performed, and the labeling index (LI) was calculated to investigate the correlation with COX‐2. To confirm COX‐2 mRNA, the authors performed ISH in 20 IPMT patients. RESULTS COX‐2 was positive in 0%, 0%, and 10% of pancreatic duct epithelial cells from normal pancreatic tissue, chronic pancreatitis, and IPMT hyperplasia, respectively. Whereas it was positive in 69%, 77%, 67%, and 80% of IPMT adenoma, IPMT noninvasive adenocarcinoma, IPMT invasive adenocarcinoma, and ductal pancreatic adenocarcinoma, respectively, showing significant differences between IPMT hyperplasia and IPMT adenoma or IPMT adenocarcinoma (noninvasive and invasive adenocarcinoma). In the same patient, COX‐2 was negative in the hyperplasia region but positive in adenoma and adenocarcinoma regions, showing results reflecting the progression of the disease. In the COX‐2 negative group, PCNA‐LI was 19.2 ± 17.9%, and 33.5 ± 15.7% in the positive group, a significant difference. On ISH, COX‐2 mRNA was expressed in three of four and seven of eight COX‐2 positive patients with IPMT adenoma and adenocarcinoma, respectively. CONCLUSIONS COX‐2 was highly expressed in adenoma and adenocarcinoma in IPMT, showing a relation to the histologic grade of IPMT. Cancer 2002;94:1565–73. © 2002 American Cancer Society. DOI 10.1002/cncr.10358