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

关于卵巢癌发生的早期致病过程知之甚少，因为在晚期诊断出超过一半的卵巢癌患者。卵巢上皮肿瘤起源于卵巢的表面上皮，有三种类型的临床病理学。良性囊肿瘤，低恶性势（LMP）和浸润性癌的肿瘤。然而，尚不清楚卵巢癌是由于卵巢的良性或LMP肿瘤的恶性转化而在卵巢表面还是发育。为了解决这个问题，我们详细研究了卵巢癌发展的临床课程，以及有关卵巢肿瘤遗传改变的异质性的分子病理分析。此外，我们研究了各种基因在肿瘤进展方面的表达。对不育患者的卵巢癌发育的临床发现的分析表明，浆液性癌经常处于…首次认识到肿瘤时更高级的阶段，同时是子宫内膜类药物或透明细胞癌在内瘤癌症中出现的较早阶段的早期阶段是早期的。促性腺激素受体在卵巢癌中的表达以及促性腺激素在卵巢癌细胞中凋亡的抑制作用表明，促性腺激素在卵巢癌中起着重要作用粘膜癌中异质。根据组织病理学，K-RAS突变的肿瘤细胞也异质。这些发现表明，在卵巢表面的浆液性癌从头出现，而粘膜癌在良性或LMP肿瘤中发展。c-erbb-2基因的表达以及改善转移相关的NM23基因的表达对卵巢癌的远处转移都很重要。但是，NM23基因突变在卵巢癌中很少见。血管内皮生长因子（VEGF）的过表达可能在腹膜参与卵巢癌中起着至关重要的作用，而血清VEGF水平是卵巢癌患者的一种新型肿瘤标记。较少的

项目成果

Mandai, M., Konishi, I., et al.: "Messenger ribonucleic acid expression of LH/hCG receptor gene in humaan ovarian carcinomas." Eur J Cancer. (in press). (1997)

Mandai, M., Konishi, I., et al.：“人类卵巢癌中 LH/hCG 受体基因的信使核糖核酸表达。”

Kobayashi, F., Konishi, I., et al.: "Rapid growth of ovarian clear cell carcinomas expressing LH/hCG receptor arising from endometriosis during early pregnancy." Gynecol Oncol. 62. 309-313 (1996)

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。”

Konishi, I.: "Review : infertility therapy and ovarian carcer." Adv Obstet Gynecol. 48. 387-395 (1996)

Konishi, I.：“回顾：不孕症治疗和卵巢癌。”

Koshiyama, M., Konishi, L., et al.: "Immunohistochemical analysis of p53 protein and 72 kDa heat shock protein (HSP72) expression in ovarian carcinomas : correlation with clinicopathology and sex steroid receptor status." Virchows Archiv. 425. 603-609 (19

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。”

Mandai, M., Konishi, I., et al.: "Mutation of the nm23 gene, loss of heterozygosity at the nm23 locus and K-ras mutation in ovarian carcinoma : correlation with tumour progression and nm23 gene expession." Br J Cancer. 72. 691-695 (1995)

Mandai, M., Konishi, I., et al.：“卵巢癌中 nm23 基因突变、nm23 位点杂合性缺失和 K-ras 突变：与肿瘤进展和 nm23 基因表达的相关性。”