Immunohistochemical Analysis of p27 (Kip1) in Human Pituitary Glands and in Various Types of Pituitary Adenomas

Abstract

p27 (Kip1) plays regulatory roles in the cell cycle by inhibiting the activity of cyclin dependent kinases (CDKs). This immunohistochemical study is aimed at elucidating the expression of p27 in human pituitary and in various types of pituitary adenomas in order to clarify its role in the regulation of proliferation. Sixteen normal pituitary glands and 179 human pituitary adenomas were used for immunohistochemical studies. The tissues were fixed in 10% formalin and embedded in paraffin. Indirect peroxidase method was performed after heat-induced antigen retrieval using a monoclonal antibody against p27 protein. p27 protein was expressed in the nuclei of all 16 normal human pituitary glands. p27 protein was also expressed in 128 of 179 cases of pituitary adenomas (71.5%). A marked decrease of p27 expression was noted in ACTH-secreting adenomas, 8/20 (40.0%), compared with other types of pituitary adenomas--GH-secreting adenomas, 35/46 (76.1%); PRL-secreting adenomas, 22/33 (66.7%); TSH-secreting adenomas, 8/11 (72.7%); and nonfunctioning adenomas, 55/69 (79.7%). These results suggest that p27 may play some role in the regulation of proliferation in all types of pituitary adenomas. The lower levels of p27 in ACTH-secreting adenoma is of particular interest with respect to the intermediate lobe-derived pituitary tumor developed in p27 knockout mice.

Attenuated expression of menin and p27 Kip1 in an aggressive case of multiple endocrine neoplasia type 1 (MEN1) associated with an atypical prolactinoma and a malignant pancreatic endocrine tumor

“…Furthermore, we found levels of MEN1 and p27 mRNAs to be low in the recurrent prolactinoma. Although most of previous studies reported low expression of p27 in the sporadic pituitary adenomas, expression levels of menin and MEN1 mRNA have been inconsistent [20][21][22][23][24][25][26][27]. The discrepancy between our data and previous reports may be due to the different antibody used for immunocytochemistry or the method for real-time PCR; we used TaqMan probes and others used regular RT-PCR and semiquantitative analysis.…”

Somatostatin analogues stimulate p27 expression and inhibit the MAP kinase pathway in pituitary tumours

“…Overexpression of p27 leads to cell-cycle arrest (7), while lack of p27 results in pituitary adenomas in p27 'knockout' animals (8)(9)(10). We, and others, have previously shown reduced expression of p27 in a variety of pituitary adenomas (11)(12)(13)(14)(15), although a single study was not able to confirm this (16).…”

Molecular and Histological Studies of Pituitary Tumorigenesis Using Experimental Animal Models

“…Disruption of p27, which is a member of the CIP1/KIP1 family, in mice resulted in tumors of the pituitary intermediate lobe and multi-organ hyperplasia [24,38]. Interestingly, immunohistochemical study of human pituitary adenomas showed that the level of p27 expression in ACTHoma was markedly lower compared with other types of pituitary adenomas [26]. These findings suggest the intermediate lobe specific role of p27.…”