Authors: F Kimura J Watanabe H Hata T Fujisawa Y Kamata Y Nishimura T Jobo H Kuramoto
Publish Date: 2003/12/20
Volume: 130, Issue: 3, Pages: 161-168
Abstract
PTEN is a tumor suppressor gene that inhibits cell proliferation by regulating intracellular signaling pathways and this activity can be abolished by mutations of the PTEN gene This study was designed to examine the correlation of PTEN expression with the expression of cell cycle regulators and with clinicopathological parameters in endometrioid adenocarcinoma of the uterine corpusTissue samples of 117 endometrioid adenocarcinomas in addition to those of 19 normal endometria and 20 endometrial hyperplasias were used for the study Immunohistochemical staining for PTEN protein was performed with the labeled streptavidinbiotin method on formalinfixed and paraffinembedded tissue samples PTEN expression was represented as the staining scoreImmunohistochemistry showed that the nuclei of cells were positive for PTEN The PTEN staining score of normal endometrium was significantly higher in the proliferative phase than in the secretory phase The scores of various endometrial hyperplasias were not significantly different from each other regardless of the type of hyperplasia The PTEN staining scores of endometrioid adenocarcinomas were 76±52 in G1 96±52 in G2 and 119±37 in G3 and increased significantly as the histological grade increased PTEN staining score was not significantly correlated with clinicopathological parameters such as FIGO stage myometrial invasion lymphvascular space invasion LVSI lymph node metastasis or group but was significantly correlated with labeling indices LIs of cell cycle regulators such as Ki67 cdk2 cyclin A cyclin D1 cyclin E p27 and p53 The PTEN staining score of p53wild cases was significantly lower than that of p53mutant ones but there was no significant difference of the score in cases with different PTEN gene status PTEN expression was significantly lower in cases with both high levels of estrogen receptor and progesterone receptorPTEN protein expression was decreased in welldifferentiated and less growthaggressive endometrial carcinoma with wildtype p53 gene and high levels of ER and PR This suggests that disturbed PTEN expression occurs in an early phase of the tumorigenesis of welldifferentiated endometrial carcinomaThis work was supported by grantsinaid for the Project Research of Graduate School of Medical Sciences Kitasato University Grants 2005 and 4007 and for Scientific Research from the Ministry of Education Culture Sports Sciences and Technology Grants 12670176 and 12671627 Japan
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