Immunohistochemical analysis of cyclooxygenase (COX)-2 expression in pancreatic endocrine tumors: association with tumor progression and proliferation.

An immunohistochemical study of cyclooxygenase (COX)-2 expression in pancreatic endocrine tumors (PET) was carried out, and the expression of COX-2 was compared with pathological features, the expression of several markers (hormones, vascular endothelial growth factor, single-stranded DNA, and the Ki-67 labeling index [LI]). Twenty PET, including 10 metastasizing cases (tumor size: 3-8 cm) and 10 non-metastasizing cases (tumor size: 0.3-8 cm) were studied. Tumors with a high level of COX-2 expression were placed in the H group, and the remaining tumors were placed in the L group. The H group was comprised of 13 tumors: all 10 of the metastasizing cases and three of the non-metastasizing cases. There were significant differences in tumor size between the two groups (H group 46.5 mm; L group 0.9 mm). There were significant differences in the presence of the following histological criteria for malignancy: pleomorphism (H group 13/13; L group 1/7), mitotic activity (H group 2.9; L group 0) and/or angioinvasion (H group 13/13; L group 1/7); and there were also significant differences in the number of cases that expressed ectopic hormones (gastrin, vasoactive intestinal peptide, serotonin and calcitonin; H group 12/13; L group 2/7) and in the Ki-67 LI (H group 8.3%; L group 0.4%). The distribution of COX-2-positive cells tended to be similar to the distribution of Ki-67-positive cells. Our data show that COX-2 is frequently upregulated in malignant PET and that there is a close relationship between COX-2 expression and tumor progression/proliferative activity.