Zheng W, Luo M P, Welt C, Lambert-Messerlian G, Sung C J, Zhang Z, Ying S Y, Schneyer A L, Lauchlan S C, Felix J C
Department of Pathology, University of Southern California, School of Medicine, Los Angeles 90033, USA.
Gynecol Oncol. 1998 Apr;69(1):23-31. doi: 10.1006/gyno.1998.4958.
Inhibins and activins are related gonadal peptides with opposing biologic actions on gonadotropin regulation, cell differentiation, and proliferation. The previous study of activin in ovarian cancer cell lines suggests that activin may promote growth of ovarian cancer. Elevated serum inhibin levels were also found in ovarian cancer patients; however, the source of elevated inhibin is unknown. This study is designed to examine the expression of inhibin and activin subunits as well as activin receptor in primary ovarian epithelial tumors to explore their role in the process of ovarian epithelial tumorigenesis.
The protein and mRNA expression of alpha and betaA subunits of inhibin/activin as well as of activin receptor mRNA were examined with immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) in 112 ovarian carcinomas. Cases included 59 serous, 23 endometrioid, 16 mucinous, 9 clear cell, and 5 undifferentiated carcinomas. We also tested normal ovary and benign and borderline ovarian tumors for comparison. These included 17 ovarian surface epithelial samples, 6 serous and 5 mucinous cystadenomas, and 9 serous and 7 mucinous tumors of low malignant potential. A total of 139 ovarian tumors were analyzed by IHC and a total of 63 ovarian tumor samples were tested by RT-PCR.
Inhibin alpha subunit expression was found in 47% of ovarian surface epithelia and focal alpha immunoreactivity was seen in tumor stroma, but was not found in the epithelial component of ovarian cystadenomas, tumors of low malignant potential (LMP), or carcinomas. Activin betaA subunit was expressed in 93% of surface epithelia, in the epithelial component of all cystadenomas, in 81% of LMP tumors, and in 72% of carcinomas, but not in tumor stroma. Activin expression did not correlate with histologic grades, tumor types, and surgical stages. Activin receptor type I and II mRNA-amplified products were found in virtually all the surface epithelial samples and ovarian tumors.
The data suggest that imbalanced expression of inhibin and activin subunits in ovarian surface epithelium may represent an early event which leads to epithelial proliferation. Unopposed betaA and activin receptor expression in epithelial compartment of ovarian tumors suggest that activin may be available as autocrine and/or paracrine factors in ovarian epithelial tumors. But exact roles of inhibin and activin in ovarian epithelial tumors remain to be defined.
抑制素和激活素是相关的性腺肽，对促性腺激素调节、细胞分化和增殖具有相反的生物学作用。先前对卵巢癌细胞系中激活素的研究表明，激活素可能促进卵巢癌的生长。在卵巢癌患者中也发现血清抑制素水平升高；然而，抑制素升高的来源尚不清楚。本研究旨在检测原发性卵巢上皮性肿瘤中抑制素和激活素亚基以及激活素受体的表达，以探讨它们在卵巢上皮肿瘤发生过程中的作用。
采用免疫组织化学（IHC）和逆转录-聚合酶链反应（RT-PCR）检测112例卵巢癌中抑制素/激活素α和βA亚基的蛋白及mRNA表达以及激活素受体mRNA表达。病例包括59例浆液性癌、23例子宫内膜样癌、16例黏液性癌、9例透明细胞癌和5例未分化癌。我们还检测了正常卵巢以及卵巢良性和交界性肿瘤作对照。这些包括17例卵巢表面上皮样本、6例浆液性和5例黏液性囊腺瘤，以及9例低恶性潜能浆液性肿瘤和7例黏液性肿瘤。共139例卵巢肿瘤通过免疫组织化学进行分析，共63例卵巢肿瘤样本通过RT-PCR进行检测。
在47%的卵巢表面上皮中发现抑制素α亚基表达，在肿瘤间质中可见局灶性α免疫反应性，但在卵巢囊腺瘤、低恶性潜能（LMP）肿瘤或癌的上皮成分中未发现。激活素βA亚基在93%的表面上皮、所有囊腺瘤的上皮成分、81%的LMP肿瘤和72%的癌中表达，但在肿瘤间质中不表达。激活素表达与组织学分级、肿瘤类型和手术分期无关。几乎在所有表面上皮样本和卵巢肿瘤中都发现了激活素I型和II型受体mRNA扩增产物。
数据表明，卵巢表面上皮中抑制素和激活素亚基的表达失衡可能是导致上皮增殖的早期事件。卵巢肿瘤上皮区中βA和激活素受体的无对抗表达表明，激活素可能作为卵巢上皮肿瘤中的自分泌和/或旁分泌因子。但抑制素和激活素在卵巢上皮肿瘤中的确切作用仍有待确定。
