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Expression of steroid receptor coactivators and corepressors in human endometrial hyperplasia and carcinoma with relevance to steroid receptors and Ki-67 expression

✍ Scribed by Junko Uchikawa; Tanri Shiozawa; Hsien-Chang Shih; Tsutomu Miyamoto; Yu-Zhen Feng; Hiroyasu Kashima; Kenji Oka; Ikuo Konishi

Publisher
John Wiley and Sons
Year
2003
Tongue
English
Weight
280 KB
Volume
98
Category
Article
ISSN
0008-543X

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✦ Synopsis

Abstract

BACKGROUND

To examine the steroid hormone dependent growth mechanism of human endometrial hyperplasia and carcinoma, expression levels of steroid receptor cofactors, such as coactivators (steroid receptor coactivator 1 [SRC‐1] and p300/cyclic AMP‐response element‐binding protein (p300/CBP]) and corepressors (nuclear receptor corepressor [NCoR] and silencing mediator for retinoid and thyroid‐hormone receptors [SMRT]), were investigated.

METHODS

The expression levels of cofactors were examined immunohistochemically using 20 samples of normal endometria, 36 samples of hyperplastic endometria, and 58 of malignant endometria and were compared with the expression levels of estrogen receptor (ER), progesterone receptor (PR), and a proliferation marker, Ki‐67.

RESULTS

In samples of normal endometria, the expression of coactivators was observed diffusely in glandular cells in the proliferative phase, with a mean positivity index (PI) of 81.8 for SRC‐1 and 91.3 for p300/CBP, whereas expression levels decreased in endometrial hyperplasia (PI: SRC‐1, 58.9; p300/CBP, 83.8) and endometrial carcinoma (PI: SRC‐1, 45.0; p300/CBP, 55.4). In endometrial hyperplasia, there was a significant correlation between the expression of ER and SRC‐1 or p300/CBP. In contrast, there were no significant statistical or topologic correlations between the expression of coactivators and the expression of ER/PR in endometrial carcinoma. The expression of corepressors generally was limited, except for elevated expression of NCoR in endometrial hyperplasia (PI, 23.8).

CONCLUSIONS

The current study showed that expression levels of the steroid receptor coactivators SRC‐1 and p300/CBP were reduced in endometrial carcinoma compared with normal and hyperplastic endometrium. In addition, topologic coexpression of both coactivators and ER/PR was lost in endometrial carcinoma. Accordingly, limited response to sex steroids in patients with endometrial carcinoma may be ascribed to the dissociation of cofactors and ER/PR. Cancer 2003. © 2003 American Cancer Society.

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