Cao Shi-Nian, Chang Ki-Hong, Luthra Rajyalakshmi, Liu Jinsong
Department of Pathology, The University of Texas Medical School-Houston, Houston, Texas, USA.
Mod Pathol. 2003 Oct;16(10):1048-52. doi: 10.1097/01.MP.0000089781.66207.D6.
The purpose of this study was to determine whether mutations in the Bax gene play a role in the development of ovarian endometrioid carcinoma with a microsatellite instability phenotype. We analyzed a total of 60 tumor specimens, 49 ovarian endometrioid carcinomas and 11 concurrent endometrial endometrioid carcinomas from 49 patients. Fourteen ovarian endometrioid carcinomas and 6 endometrial endometrioid carcinomas showed a microsatellite instability-high phenotype. Tumor and normal-tissue specimens from eight patients with a microsatellite instability-high phenotype colorectal carcinoma were included in this study as controls. The presence or absence of a mutation in the poly (G) 8 tract of the Bax gene was determined by polymerase chain reaction followed by direct DNA sequence analysis. A 1-base pair deletion at the poly (G) 8 tract and no expression of Bax and Bcl-2 proteins were identified in one microsatellite instability-high endometrial endometrioid carcinoma. Immunohistochemical staining for Bax and Bcl-2 proteins was negative on the tumor specimen that had this 1-base pair deletion. No mutations were found in the synchronous microsatellite instability-high ovarian endometrioid carcinoma from the same patient. In contrast, four (50%) of the eight microsatellite instability-high sporadic colorectal carcinomas had a mutation in the poly (G) 8 tract. Although Bax plays an important role in carcinogenesis of the colorectum with microsatellite instability-high phenotype, Bax may not play a direct role in the genesis of ovarian endometrioid carcinoma, regardless of microsatellite instability status.
本研究的目的是确定Bax基因的突变是否在具有微卫星不稳定表型的卵巢子宫内膜样癌的发生发展中起作用。我们共分析了60个肿瘤标本，其中包括来自49例患者的49个卵巢子宫内膜样癌和11个同期子宫内膜子宫内膜样癌。14个卵巢子宫内膜样癌和6个子宫内膜子宫内膜样癌表现为微卫星高度不稳定表型。本研究纳入了8例微卫星高度不稳定表型结直肠癌患者的肿瘤及正常组织标本作为对照。通过聚合酶链反应及直接DNA序列分析来确定Bax基因多聚（G）8序列是否存在突变。在1例微卫星高度不稳定的子宫内膜子宫内膜样癌中，发现多聚（G）8序列有1个碱基对缺失，且未检测到Bax和Bcl-2蛋白表达。对存在该1个碱基对缺失的肿瘤标本进行Bax和Bcl-2蛋白免疫组化染色均为阴性。在同一患者的同步微卫星高度不稳定的卵巢子宫内膜样癌中未发现突变。相比之下，8例微卫星高度不稳定的散发性结直肠癌中有4例（50%）多聚（G）8序列存在突变。尽管Bax在微卫星高度不稳定表型的结直肠癌发生中起重要作用，但无论微卫星不稳定状态如何，Bax可能在卵巢子宫内膜样癌的发生中不发挥直接作用。
