Department of Pathology, Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau), Autonomous University of Barcelona, 08041 Barcelona, Spain.
Department of Pathology, Università degli Studi di L'Aquila, 67010 Coppito-L'Aquila, Italy.
Hum Pathol. 2018 Oct;80:11-27. doi: 10.1016/j.humpath.2018.06.018. Epub 2018 Jun 23.
Based on histopathology and molecular genetics, ovarian carcinomas are divided into five main types: high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3%), and low-grade serous (<5%) carcinomas. These tumors, which account for over 95% of cases, represent distinct diseases with different prognoses and treatments. TP53 mutations are identified in almost all (96%) high-grade serous carcinomas (HGSCs). Early p53 loss followed by BRCA loss leads to deficiency in homologous recombination (DHR) repair, which in turn triggers chromosomal instability and widespread somatic copy number changes. An undetermined number of cases of HGSCs originate in the tubal fimbria; however, an origin from the ovarian surface epithelium cannot be totally excluded. Low-grade serous carcinomas (LGSCs) most likely represent progression of SBTs. BRAF or KRAS mutations occur in one-third to one-half of cases. Mucinous carcinomas (MCs) typically show benign-appearing, borderline, non-invasive and invasive components indicating tumor progression. KRAS mutations occur in 43.6% of cases and overexpression/amplification of HER2 in 18.8%. Endometrioid and clear cell carcinomas (EC and CCC) originate from ovarian endometriosis. Compared with their uterine counterparts, ECs have a similar frequency of β-catenin abnormalities but lower rate of microsatellite instability (MI) and PTEN alterations. ARID1A mutations occur in both ECs (30%) and CCCs (50%) and may be encountered in adjacent endometriosis. CCCs carry inactivating PTEN mutations and activating mutations in PIK3CA in 8% and 33% of cases, respectively. This review summarizes recent advances in the molecular pathology, which have greatly improved our understanding of the biology of ovarian carcinomas and are also relevant to patient management.
根据组织病理学和分子遗传学，卵巢癌分为五个主要类型：高级别浆液性（70%）、子宫内膜样（10%）、透明细胞（10%）、黏液性（3%）和低级别浆液性（<5%）癌。这些肿瘤占病例的 95%以上，代表着不同的疾病，具有不同的预后和治疗方法。几乎所有（96%）高级别浆液性癌（HGSCs）都存在 TP53 突变。早期 p53 缺失，随后 BRCA 缺失，导致同源重组（HR）修复缺陷，进而引发染色体不稳定和广泛的体细胞拷贝数变化。大量的 HGSCs 起源于输卵管伞端，但不能完全排除卵巢表面上皮的起源。低级别浆液性癌（LGSCs）可能代表 SBT 的进展。BRAF 或 KRAS 突变发生在三分之一到一半的病例中。黏液性癌（MCs）通常表现为良性、交界性、非浸润性和浸润性成分，提示肿瘤进展。KRAS 突变发生在 43.6%的病例中，HER2 过表达/扩增发生在 18.8%的病例中。子宫内膜样和透明细胞癌（EC 和 CCC）起源于卵巢子宫内膜异位症。与子宫对应物相比，EC 具有相似的β-catenin 异常频率，但微卫星不稳定性（MSI）和 PTEN 改变的频率较低。ARID1A 突变发生在 EC（30%）和 CCC（50%）中，也可能发生在相邻的子宫内膜异位症中。CCC 携带失活的 PTEN 突变和激活的 PIK3CA 突变，分别在 8%和 33%的病例中。这篇综述总结了分子病理学的最新进展，这些进展极大地提高了我们对卵巢癌生物学的理解，也与患者管理有关。
