Molecular-pathologic and clinicopathologic study on the heterogeneity of early development and progression of ovarian cancer

卵巢癌早期发生发展异质性的分子病理学和临床病理学研究

• 批准号: 07457608
• 负责人: KONISHI Ikuo
• 金额: $ 0.96万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457608/
• 关键词: ovarian cancer; carcinogenesis; heterogeneity; p53; K-ras; nm23; VEGF; gonadotropin; 性ステロイド受容体

Little is known about the early pathogenic process of ovarian carcinogenesis, because more than half of ovarian cancer patients are diagnosed at the advanced stages. Ovarian epithelial tumors originate from the surface epithelium covering the ovary, and there are three types with distinct clinicopathology ; benign cystadenoma, tumor of low malignant potential (LMP), and invasive carcinoma. However, it is unknown whether ovarian carcinomas occur de novo in the ovarian surface or develop as a result of the malignant transformation of benign or LMP tumors of the ovary. To address this issue, we studied the clinical course in detail of ovarian cancer development, and molecular pathologic analysis on heterogeneity of genetic alterations in ovarian tumors. In addition, we examined the expression of various genes with reference to the tumor progression.Analysis of the clinical findings of ovarian cancer development in infertility patients revealed that serous carcinomas are frequently at the … More advanced stages when the tumor was first recognized, whereas endometrioid or clear cell carcinomas arising in endometriotic cyst are at the early stage. Expression of gonadotropin receptors in ovarian cancers and apoptosis-inhibitory effect of gonadotropins in ovarian cancer cells suggest that gonadotropins play an important role in ovarian carcinogenesis.Immunohistochemical analysis of p53 protein expression in ovarian tumors showed that p53-positive tumor cells are homogeneously distributed in serous carcinomas, whereas heterogeneous in mucinous carcinomas. K-ras-mutated tumor cells are also heterogeneously present in accordance with histopathology. These findings suggest that serous carcinomas arise de novo in the ovarian surface, whereas mucinous carcinomas develop in the benign or LMP tumors.Overexpression of C-erbB-2 gene and decreased expression of metastasis-related nm23 gene are both important for distant metastasis of ovarian carcinomas. However, nm23 gene mutation is rare in ovarian carcinomas. Overexpression of vascular endothelial growth factor (VEGF) may play an essential role in peritoneal involvement with ascites formation in ovarian carcinomas, and serum VEGF levels is a novel tumor marker in ovarian cancer patients. Less

人们对卵巢癌的早期发病过程知之甚少，因为一半以上的卵巢癌患者确诊时已是晚期。卵巢上皮性肿瘤起源于覆盖卵巢的表面上皮，分为临床病理各异的三种类型；良性囊腺瘤、低度恶性潜能肿瘤（LMP）和浸润性癌。然而，尚不清楚卵巢癌是在卵巢表面从头发生还是由于卵巢良性或LMP肿瘤恶变而发展。为了解决这个问题，我们详细研究了卵巢癌发展的临床过程，并对卵巢肿瘤遗传改变的异质性进行分子病理学分析。此外，我们还根据肿瘤进展检查了各种基因的表达。对不孕症患者卵巢癌发展的临床结果进行分析后发现，浆液性癌在首次发现肿瘤时常常处于晚期，而子宫内膜异位囊肿中出现的子宫内膜样癌或透明细胞癌则处于早期阶段。卵巢癌中促性腺激素受体的表达以及促性腺激素对卵巢癌细胞的凋亡抑制作用提示促性腺激素在卵巢癌发生过程中发挥着重要作用。卵巢肿瘤中p53蛋白表达的免疫组化分析显示，p53阳性肿瘤细胞均匀分布在浆液性癌中，而p53阳性肿瘤细胞在浆液性癌中均匀分布，而 粘液癌中存在异质性。根据组织病理学，K-ras 突变的肿瘤细胞也存在异质性。这些发现表明浆液性癌在卵巢表面从头产生，而粘液性癌在良性或LMP肿瘤中发展。C-erbB-2基因的过度表达和转移相关nm23基因的表达减少对于卵巢癌的远处转移都很重要。然而，nm23基因突变在卵巢癌中很少见。血管内皮生长因子（VEGF）的过度表达可能在卵巢癌腹膜受累和腹水形成中发挥重要作用，血清VEGF水平是卵巢癌患者的一种新的肿瘤标志物。较少的

项目成果

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Koshiyama, M.、Konishi, L. 等人：“卵巢癌中 p53 蛋白和 72 kDa 热休克蛋白 (HSP72) 表达的免疫组织化学分析：与临床病理学和性类固醇受体状态的相关性。”

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Kobayashi, F., Konishi, I., et al.：“妊娠早期子宫内膜异位症引起的表达 LH/hCG 受体的卵巢透明细胞癌的快速生长。”

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