上皮性卵巢癌起源二元论及分子生物学基础

上皮性卵巢癌是卵巢恶性肿瘤中最常见的类型，也是恶性程度最高的妇科肿瘤，基于近年来一系列的形态学和分子遗传学研究可将上皮性卵巢癌分为Ⅰ型和Ⅱ型。卵巢低级别浆液性腺癌属Ⅰ型来自交界性肿瘤，主要表现为微乳头形态伴KRAS和BRAF基因的突变，肿瘤呈渐进性发展，惰性病程，诊断时多数处于临床早期，预后较好。高级别浆液性腺癌属Ⅱ型，细胞异型性显著，多伴TP53突变，卵巢自身见不到前驱病变，呈高度侵袭性病程，多数来自输卵管伞端上皮的浆液性病变，确诊时常已处于临床晚期，发病快，生长迅速，侵袭性强，预后差。I型及II型卵巢癌表现出的生物学特性不同，在临床表现、预后等方面的明显差异提示了二者可能具有不同的起源及遗传学改变。本文将从分子遗传学角度对近期研究理论并从“二元”角度来探讨上皮性卵巢癌的起源进行综述。 

Two-tier system on the origin of epithelial ovarian carcinomas and associated molecular biological basis

Ovarian epithelial carcinomas are the most common lethal gynecological malignancies. Ovarian carcinomas are divided into Types I and II based on different morphologies, genetic alterations, and biomarker expression. Low-grade micropapillary serous carcinoma are Type I tumors. Type I tumors are slow growing, generally confined to the ovary at diagnosis, and with better prognosis. These tumors develop from well established precursor lesions that are termed "borderline" tumors. Type 1 tumors are genetically stable and are characterized by mutations in a number of different genes including KRAS, BRAF, PTEN, and beta-catenin. Type II tumors are rapidly growing and highly aggressive neoplasms, for which well defined precursor lesions have not been described. They may arise in the fimbrial epithelium of the oviduct with advanced stage, more aggressive behavior, and worse prognosis. High-grade serous carcinoma belongs to Type II tumors. This group of tumors has a high level of genetic instability and is characterized by TP53 mutation. Hence, ovarian cancer comprises a heterogeneous group of tumors with distinctly different histological characteristics, molecular genetic features, and clinical course.