Cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) expression in human pituitary macroadenomas.

Abstract

Macroadenomas are tumors of the pituitary gland and are considered almost to be always benign and curable. The clinical manifestations of a pituitary tumor depend on the hormone secreted by the tumor as well as on the pattern of tumor growth within the sella turcica. Current trends attempt to target new molecular markers that also may serve as potential therapeutic targets. Cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) are upregulated in a number of epithelial tumors. No published reports exist about expression of COX-2 in pituitary macroadenomas, and only a few reports with differing results exist concerning EGFR expression in pituitary macroadenomas. This study sought to determine whether a relationship exists between COX-2 and EGFR expression and pituitary macroadenomas. Thirty specimens of pituitary macroadenomas were evaluated after being identified in the surgical pathology database of Thomas Jefferson University Hospital. The hematoxylin and eosin-stained slides were reviewed, and the representative paraffin blocks containing the index case were chosen and immunohistochemically stained for COX-2 and EGFR expression. The COX-2 and EGFR-stained slides were reviewed and an immunohistochemical score was calculated and analyzed. The pituitary macroadenomas were classified on the basis of hormone expression: none (nonsecreting), minor (nondominant, plurihormonal), single (dominant nonplurihormonal), or plurihormonal (dominant plurihormonal). The hormonal classification was then analyzed for association with COX-2 expression. COX-2 expression was significantly associated with plurihormonal pituitary macroadenomas (p value 0.03). COX-2 expression was significantly associated with expression of luteinizing hormone (p value 0.007) and with expression of thyroid-stimulating hormone (TSH) (p value 0.04). Additionally, COX-2 expression was significantly associated with single-hormone of pituitary adenoma (p value 0.049). The expression of COX-2 in 100% of the normal autopsy pituitary glands establishes an additional central nervous system location of COX-2 expression. EGFR was not expressed in any of the pituitary macroadenomas. The expression of COX-2 in plurihormonal pituitary macroadenomas, particularly those secreting TSH, may be a potential target for treatment in addition to surgical and/or radiotherapy treatment in these benign but clinically significant tumors. COX-2 is expressed in normal autopsy pituitary tissue.