Cyclooxygenase-2 expression in human pituitary tumors

Abstract

Background: Cyclooxygenase-2 (COX-2) plays a role in progression of colon, breast, pancreas, and lung carcinomas. The authors investigated COX-2 expression in pituitary tumors.

Methods: Expression of COX-2 was evaluated in 164 surgically removed human pituitary tumors. Correlation of COX-2 with MIB-1, a cell proliferation marker, as well as angiogenesis, patient age, gender, tumor type, size, invasiveness, and metastatic potential was investigated.

Results: Cyclooxygenase-2 immunoreactivity was confined to the cytoplasm of tumor cells, whereas the nuclei were unlabeled. Few normal peritumoral adenohypophysial cells showed slight COX-2 cytoplasmic immunoreactivity. The staining intensity and the percentage of immunopositive cells were higher in tumors. Most pituitary tumors (96%) were COX-2-immunopositive. Expression was strong in 60 (44%), moderate in 39 (28%), and weak in 32 (24%). Male gonadotroph adenomas and null cell adenomas showed a high level of COX-2 expression. Growth hormone-producing adenomas, prolactin-producing adenomas, thyrotropic hormone-producing adenomas, female gonadotroph adenomas, silent adrenocorticotropic hormone-producing adenomas, and silent subtype 3 adenomas had a low level of COX-2 expression. Significant correlation was demonstrated with patient age, but not with tumor size, invasiveness, and MIB-1 labeling indices. Expression was medium to high in 76% of macroadenomas and in only 45% of microadenomas. Strong correlations were noted with angiogenesis markers, such as microvessel density and surface density.

Conclusions: Correlation with angiogenesis suggests that COX-2 may be involved in the regulation of angiogenesis in pituitary tumors. Phamacologic inhibition of COX-2 activity might suppress angiogenesis in pituitary tumors and may provide a novel approach for medical therapy.