The Expression Of Estrogen Related Factors In Serous Ovarian Cancer And The Clinical Significance

Background: The disorder of local estrogen synthesis, estrogen dependent genic regulator control system and the expression of some estrogen induced proteins may lead to the occurrence and progression of estrogen related tumors. Ovarian cancer is the most lethal gynecologic neoplasm, over 90% of which originate from ovarian surface epithelial cells. Evidence from experiment in vitro , epidemiological data and clinical tests suggested that estrogen correlate with the epithelial ovarian cancer(EOC). But the roles local estrogen plays in EOC are not yet determined. Aromatase P450(P450Arom) is the final rate-limiting enzyme in the procedure of estrogen synthesis, which, expresses in some estrogen related tumortissue and synthesize estrogen in local tumor tissue. Estrogen alpha (ERa) is the first estrogen receptor found in human bodies, With stronger capacity to bind estrogen comparison with other subtype of estrogen receptor. The genomic action of Estrogen is mediated by estrogen receptor in cells. With ER as the media, estrogen induces some special proteins synthesis through regulating gene transcription, then shows its biological effect through the special estrogen induced proteins. Cathepsin D(Cath-D) is one of the most important estrogen induced protein . As a lysosomal aspartyl protease with important functions in protein catabolism, it plays an essential role during multiple tumor progression steps , affecting cell proliferation , apoptosis, invasion and motility , stimulating vessel endothelial cell growth.P450Arom > ERa and Cath-D represent different links of synthesis and biological effect of local estrogen , Contributing to the occurrence and progression of multiple tumors. Up to now, there is still no clearly understanding about the condition of local estrogen synthesis and local biological roles in EOC and the clinical significance.Objective: l.To explore the roles the local estrogen plays in serous ovarian cancer by detecting the expression of P450arom , ER a and Cath-D in serous ovarian cancer and to analyze the correlation among the expression level of P450arom, ER a , Cath-D , 2. To evaluate the clinical significance of the expression of P450arom, ERa , Cath-D in serous ovarian cancer by analyzing the correlation of the expression level of P450arom, Cath-D, ER a and the clinicopathological factors, survival prognosis index .Material and Method: l.The subjects of this study are 49 patients diagnosed of serous ovarian cancer and undergone operations. All patients but one (IAi.d)accepted 6~8 cycle adjuvant chemotherapy after operation .Median age of the patients was 49 years (range 23 ~74years). The control team includes 50 patients diagnosed of serous cystadenoma in the same period. Median age of the patients was 46 years (range 20 ~75 years). 2. The clinicopathological parameters of all serous ovarian cancer patients were recorded, including age , menopause status, the result of primary operation, FIGO stage, histological grading, the result of ascites cytol examination,and the histological result of retroperitoneal lymph-node. All patients were followed up, and we used the level of serous CA125 and imaging evidences to define disease relapse . Two survival indexes were recorded: disease-free survival time(DFST) and overall survival time(ST). 3. Immunohistochemical method was adopted to detect the expression of P450Arom, ERa and Cath~D in serous ovarian tumor. Staining intensity was assigned with a semiquantitative H-SCORE standard. 4. All data were statistically managed with SPSS11.0 for window.Results: 1. P450Arom didn' t express in epithelial cells of the ovarian serous cystadenoma nor in serous ovarian cancer. ER a and Cath-D are expressed in both epithelial cells of ovarian serous cystadenoma and serous ovarian cancer, specific staining granular of ER a in nucleolus and the specific staining granular of Cath-D in cytoplasm. The expression level of ERa and Cath-D is higher in serous ovarian cancer than in serous cystadenoma (t= 5.24 and t=8. 89 p=0. 00). 2. The expressions of ERa and Cath-D have positive correlation in all serous ovarian tumors(y=0. 76, P=0. 00). 3.The expressions of ER a and Cath-D in different serous ovarian cancers withdifferent clinical-histopathological characteristics: only the expression of ERa shows significant difference in the cancers with different histological grading and higher ER a expression in the cancer with favorable cell differentiation (F=7. 15, P<0. 05) , while the expression of Cath-D in the serous cancers with different clinical-histopathological characteristics shows no significant difference (P >0.05) .Conclusion: 1. Changes of the expression of estrogen related factors in serous ovarian cancer are reflected in the following aspects : the expression of P450Arom protein was absent, and the expressions of ERaand Cath-D proteins were up-regulated. 2.The expression of Cath-D protein in the epithelial cells of serous ovarian cancer can' t be considered as the prognostic factor of serous ovarian cancer.