Expression of p53 protein in pituitary adenomas

Abstract

Inactivating mutations of TP53, a tumor suppressor gene, are associated with abnormal cell proliferation. Although p53 expression is common in many human malignancies, p53 protein has seldom been evaluated in pituitary tumors. When detected, the percentage of p53-positive cells is low, and, in general, it is exclusive for invasive lesions. The aim of the present study was to use immunohistochemistry to determine the presence of p53 protein in pituitary adenomas from tumor samples of 163 surgeries performed in 148 patients (40% male, 60% female). In 35% of the cases the adenoma was nonfunctional, while in the others it was associated with PRL, GH and/or ACTH endocrine hypersecretion syndrome. Macroadenomas were observed in 83.2% of the cases with available neuroimage evaluation, of which 28% invaded the cavernous, sphenoid and/or ethmoidal sinus, bone, third ventricle or subfrontal lobe. p53 protein was detected in 2/148 patients (1.3%). Immunohistochemistry was positive for PRL and GH in these cases. Due to the high percentage of invasive pituitary adenomas found in our study, the low frequency of p53 detection suggests that it is inadequate as a routine marker for aggressiveness and as a predictive factor of tumor behavior.

Aggressive prolactinoma in a child related to germline mutation in the ARYL hydrocarbon receptor interacting protein (AIP) gene

“…The presence of p53 mutations in pituitary tumors is rarely described (28), but some authors found a relationship with proliferative states (29,30). In our patient we detected positivity in 10% of the tumoral cells.…”

“…C-erb B2 expression is a marker of tumor aggressiveness in breast cancer (31), but few studies have assessed c-erbB2 in the pituitary. Our group previously reported variable c-erbB2 immunoreactivity in somatotropic and lactotrophic tumors and it might have some influence on their evolution, considering the intimate relationship between c-erb B2 and the epidermal growth factor (EGF) (28,30). We recently described a strong c-erb staining in aggressive somatotropic adenoma in the context of Familial Isolated Pituitary Adenomas (FIPA) with a 174 frameshift AIP mutation (13).…”

Invasion of the cavernous sinus space in pituitary adenomas: endoscopic verification and its correlation with an MRI-based classification

“…We did not correlate our data with p53 expression, because it does not seem to be of pathogenetic significance in pituitary tumors. 23,32,33,45,48,55,63 Tumor proliferation markers, such as the Ki-67-targeted MIB-1 labeling index, were observed by others 47 and our group 42,43,68,71,72 to correlate with more aggressive biological pituitary adenoma behavior, such as an increased growth rate and invasive growth. These recent data support our previous results, although MIB-1 did not achieve significance between the grades, most likely because all of the included tumors were macroadenomas.…”

Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry

“…Invasive pituitary adenomas are generally characterized by a higher Ki-67 proliferation index (13,14). In addition, invasive adenomas may demonstrate p53-positive nuclei, which were found to be absent in enclosed adenomas (14,23,24). The molecular mechanisms controlling cell proliferation and invasion are largely unknown, but are believed to be separate from each other (25).…”