Kupryjanczyk J, Thor A D, Beauchamp R, Poremba C, Scully R E, Yandell D W
Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
Mod Pathol. 1996 Mar;9(3):166-73.
The clonality of disseminated serous carcinoma involving the ovary, peritoneum, and, occasionally, the endometrium is controversial. Histopathologic examination alone cannot unequivocally distinguish between a monoclonal origin and a multicentric origin. Two patients with peritoneal serous carcinoma with minimal ovarian involvement (one with endometrial serous carcinoma), nine patients with stage III bilateral ovarian carcinoma, and one patient with stage III bilateral carcinosarcoma were studied for clonality. One patient with ovarian carcinoma that recurred after chemotherapy was also studied. Previous analyses of single frozen tumor specimens from these patients had identified different p53 gene mutations in each patient. To test the hypothesis that the disseminated cancers had a monoclonal origin, we assayed DNA from numerous foci from each patient to determine whether the known p53 mutation was present in each specimen. Identical mutations were detected in the tumor foci from each patient with peritoneal dissemination and minimal ovarian involvement, including one patient with an endometrial serous carcinoma as well. In all the patients with bilateral ovarian cancer, the genetic change in p53 was identical in both ovarian tumors. Genetic progression was observed in two patients, one of whom showed a loss of heterozygosity involving the p53 gene in a recurrent tumor. In the second patient, a p53 mutation not present in either ovarian tumor was detected in a metastatic tumor from the omentum. These results strongly suggest that disseminated serous carcinomas, whether primary in the ovary, endometrium, or peritoneum, are of monoclonal rather than multicentric origin; that bilateral stage III ovarian cancers are typically of monoclonal origin; and that additional genetic events involving p53 might occur during progression of these tumors.
累及卵巢、腹膜以及偶尔累及子宫内膜的播散性浆液性癌的克隆性存在争议。仅靠组织病理学检查无法明确区分单克隆起源和多中心起源。对两名腹膜浆液性癌伴卵巢轻度受累患者（其中一名患有子宫内膜浆液性癌）、九名III期双侧卵巢癌患者以及一名III期双侧癌肉瘤患者进行了克隆性研究。还对一名化疗后复发的卵巢癌患者进行了研究。此前对这些患者的单个冷冻肿瘤标本分析发现，每名患者的p53基因突变各不相同。为了验证播散性癌症起源于单克隆这一假设，我们检测了每名患者多个病灶的DNA，以确定每个标本中是否存在已知的p53突变。在每例腹膜播散且卵巢轻度受累的患者的肿瘤病灶中均检测到相同的突变，其中包括一名子宫内膜浆液性癌患者。在所有双侧卵巢癌患者中，两个卵巢肿瘤的p53基因变化均相同。在两名患者中观察到了基因进展，其中一名患者在复发肿瘤中出现了涉及p53基因的杂合性缺失。在第二名患者中，在大网膜转移瘤中检测到了两个卵巢肿瘤中均未出现的p53突变。这些结果有力地表明，播散性浆液性癌，无论原发于卵巢、子宫内膜还是腹膜，均起源于单克隆而非多中心；III期双侧卵巢癌通常起源于单克隆；并且在这些肿瘤进展过程中可能会发生涉及p53的其他基因事件。
