P53 EXPRESSION IN PITUITARY-ADENOMAS AND CARCINOMAS - CORRELATION WITH INVASIVENESS AND TUMOR-GROWTH FRACTIONS

ALTHOUGH MOST PITUITARY tumors are well differentiated, histologically benign neoplasms, their clinical behavior is known to vary greatly. T hese lesions are relentlessly aggressive in some instances yet biologi cally indolent in others, but these prognostically relevant difference s in behavior are not reflected in their histopathological appearance. As a means of identifying intrinsically aggressive pituitary tumors, we evaluated 70 pituitary adenomas and 7 primary pituitary carcinomas for their expression of the p53 gene product, a nuclear phosphoprotein whose immunohistochemical accumulation has served as an unfavorable p rognostic factor for a wide range of human neoplasms. All tumors were fully classified by immunohistochemistry and electron microscopy; aden omas were further stratified on the basis of their invasion status, th e latter being defined as gross operatively or radiologically apparent infiltration of dura or bone. Conclusive nuclear immunopositivity for p53 was identified in a total of 12 tumors, all being either invasive adenomas or primary pituitary carcinomas. A clear and highly signific ant association was evident between p53 expression and tumor behavior, as the proportion of p53-positive cases among noninvasive adenomas, i nvasive adenomas, and pituitary carcinomas was 0, 15.2, and 100%, resp ectively (X(2) = 44.72; degrees of freedom, 2; P much less than 0.001) . A comparison of previously reported growth fraction data with p53 ex pression indicated that the mean Ki-67-derived growth fraction of p53- positive tumors was significantly higher than that of p53-negative tum ors (10.41 +/- 2.20 versus 2.51 +/- 0.28%) (+/- standard error of the mean, two-sample t test for independent samples, P = 0.004). There was no apparent relationship between the functional status of the tumor a nd p53 expression; positivity was observed among somatotroph, lactotro ph, corticotroph, and clinically nonfunctioning pituitary tumors. Thes e data indicate that p53 expression, when conclusively present in pitu itary tumors, may be of some diagnostic usefulness as a marker of biol ogically aggressive behavior.