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

卵巢癌发生的早期致病过程知之甚少，因为超过一半的卵巢癌患者在晚期被诊断出来。卵巢上皮性肿瘤起源于覆盖卵巢的表面上皮，有三种不同的临床病理类型：良性囊腺瘤，低恶性潜能肿瘤（LMP）和浸润性癌。然而，目前尚不清楚卵巢癌是在卵巢表面原发还是由于卵巢良性或LMP肿瘤的恶性转化而发展。为了解决这个问题，我们研究了卵巢癌的临床过程中详细的发展，并在卵巢肿瘤的遗传变异的异质性的分子病理学分析。此外，我们还检测了与肿瘤进展有关的各种基因的表达。对不孕症患者卵巢癌发展的临床研究结果的分析表明，浆液性癌经常发生在卵巢癌的早期阶段。 ...更多信息 当肿瘤首次被发现时，肿瘤处于晚期，而在增生性囊肿中产生的类增生性或透明细胞癌处于早期。促性腺激素受体在卵巢癌中的表达及促性腺激素对卵巢癌细胞凋亡的抑制作用提示促性腺激素在卵巢癌的发生中起重要作用，免疫组化分析卵巢癌中p53蛋白的表达表明，p53阳性肿瘤细胞在浆液性癌中呈均匀分布，而在粘液性癌中呈不均匀分布。根据组织病理学，K-ras突变的肿瘤细胞也是异质性存在的。提示卵巢浆液性癌起源于卵巢表面，而粘液性癌起源于卵巢良性或LMP肿瘤，C-erbB-2基因过表达和转移相关基因nm 23表达降低在卵巢癌远处转移中起重要作用。然而，nm 23基因突变在卵巢癌中是罕见的。血管内皮生长因子（VEGF）的过度表达可能在卵巢癌腹水形成的腹膜受累中起重要作用，血清VEGF水平是卵巢癌患者的一种新的肿瘤标志物。少

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