Expression And Significance Of Heat Shock Protein 70, 90 In Human Normal Endometrium, Endometrial Hyperplasia And Carcinoma

OBJECTIVE: Heat shock protein (Hsp) 70 and heat shock protein 90 are the chaperoninses of steroid receptor. The expressions of Hsp70 and Hsp90 have great influence on the structure and function of steroid receptor and are closely related to the growth and pathogenesis of endometrium. Our studies focuse on the expression and significance of Hsp70 and Hsp90 in human normal endometrum, endometrial hyperplasia and carcinoma, and provide a series of experimental evidences and a novel clue for the diagnosis and treatment of endometrial disease.METHODS: (1) The expressions of Hsp70, Hsp90 and ER in different endometrium were examined by DAKO-Envision immunohistochemical analysis and computerized image analysis system. (2) Effect of estrogen on the expression of Hsp70 and Hsp90 in normal endometrial glandular epithelial cell in vitro was measured by DAKO-Envision immunohistochemical analysis and computerized image analysis system. (3) Normal endometrial glandular epithelial cell was isolated, cultured in enzymolysis method and identified by electron microscope andimmunohistochemical analysis.RESULTS: (1) Positive signals of Hsp70 and Hsp90 were yellow granules in both cytoplasm and nucleus of glandular epithelial cells and stroma cells, and the positive signals of ER were in nucleus. (2) Compared with endometrium of the secretory stage, the expression of Hsp90 and ER in proliferative phase increased (P<0.05), and Hsp70 decreased (P<0.05). (3) The expression of Hsp70, Hsp90 and ER have no differences between simple and complex endometrail hyperplasia (P>0.05). Compared with the normal endometrium of proliferative and secretory stage, the expression of Hsp90, ER increased significantly (P<0.05) while that of Hsp70 hasn't notable difference (P>0.05). (4) The expression of Hsp90, ER were down-regulated in endometrial carcinoma compared with normal endometriun of proliferative stage (P<0.05) and endometrial hyperplasia (P<0.05), while the expression of Hsp70 was up-regulated in endometrial carcinoma compared with normal endometrium of proliferative, secretory phase and endometrial hyperplasia (P<0.05). (5) The down-regulation of HSP90 and the up-regulattion of Hsp70 were related with the loss of differentiation (G1, G2, G3) (P<0.05). Expression of HSP90 in nonendometrioid-type carcinoma (adenosquamous carcinoma, clear cell carcinoma and papillary serous carcinoma) is lower than that in endometrioid-type carcinoma (P<0.05) while HSP70 was in the contrary (/><0.05). Expression of Hsp70 and Hsp90 haven't significant relation with the FIGO stage, lymph node metastasis and myometrial invasive depth (P>0.05). (6)Expression of Hsp90 has direct correlation with the expression of ER in endometrium (r=0.5715, tr=7.3369, P<0.01) and expression of Hsp70 has inverse correlation with that(r= -0.4132, tr= -4.7805, P<0.01) . (7) Estrogen treatment results in time- and does-dependent increase of the expression of Hsp90 and decrease of Hsp70 in human endometrial glandular epithelial cell. The E2-induced effects on hsp90 levels but not hsp70 levels were attenuated by the antiestrogen ICI182780.CONCLUSION: (1) Concordance between expression of Hsp90 and ER indifferent human endometrium indicates their functional dependences. Antagonizing the expression of Hsp90 and ER can attenuate the stimulative effect of estrogen on endometrium. It provides a new therapeutic target for endometrial hyperlpasia and carcinoma. (2) There was an adverse tendency between expression of Hsp70 and ER in different endometrium. The effect of estrogen on Hsp70 in endometrium was independent on ER. ER did not wholly control the expression of Hsp70. (3) The expression of Hsp70 increased and expression of Hsp90 decreased in poorly differentiated and high malignancy level endometrial carcinoma. So the expressions of Hsp70 and Hsp90 may be considered as the biological marker of prognosis. Hsp90 contributes to the estrogen stimulative effect on neoplastic tissue, and Hsp70 may protect neoplastic cells from damages and also inhibit their apoptosis. H...