Prat Jaime, Ribé Adriana, Gallardo Alberto
Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, 08025 Barcelona, Spain.
Hum Pathol. 2005 Aug;36(8):861-70. doi: 10.1016/j.humpath.2005.06.006.
Family history is the strongest risk factor for ovarian cancer. Three clinical manifestations of hereditary ovarian cancer have been recognized: (1) "site-specific" ovarian cancer, (2) the breast and ovarian cancer syndrome, and (3) the hereditary nonpolyposis colorectal cancer (HNPCC; Lynch II) syndrome. The first 2 groups are associated with germ line mutations in the BRCA1 and BRCA2 tumor suppressor genes, whereas HNPCC is associated with germ line mutations in the DNA mismatch repair (MMR) genes, primarily hMLH1 and hMSH2. At least 10% of all epithelial ovarian cancers are hereditary, with mutations in the BRCA genes accounting for approximately 90% of cases and most of the remaining 10% attributable to HNPCC. Hereditary ovarian cancers exhibit distinct clinicopathologic features compared with sporadic cancers. The cumulative lifetime risk of ovarian cancer is 40% to 50% for BRCA1 mutation carriers and 20% to 30% for BRCA2 mutation carriers. Both BRCA proteins participate in transcriptional regulation of gene expression as well as the recognition or repair of certain forms of DNA damage, particularly double-strand breaks. Mutations of BRCA1 and BRCA2 are mainly of the frameshift or nonsense variety. Most ovarian cancers associated with germ line BRCA mutations are diagnosed at a younger age and are high-grade and advanced-stage serous carcinomas. BRCA mutations do not seem to play a significant role in the development of mucinous or borderline ovarian tumors. Hereditary ovarian cancers have a distinctly better clinical outcome with longer overall survival and recurrence-free interval after chemotherapy than sporadic cancers. Women with a family history including 2 or more first- or second-degree relatives with either ovarian cancer alone or both breast and ovarian cancers should undertake prophylactic oophorectomy immediately after childbearing has been completed to reduce the risk of ovarian cancer. The cumulative risk of ovarian cancer in HNPCC families is more than 12%. Ovarian cancer in HNPCC syndrome is diagnosed at younger age than in the general population. Most tumors are low-stage well-differentiated or moderately differentiated carcinomas. Annual follow-up is recommended for these patients.
家族史是卵巢癌最强的风险因素。遗传性卵巢癌已被确认有三种临床表现：（1）“位点特异性”卵巢癌，（2）乳腺癌和卵巢癌综合征，以及（3）遗传性非息肉病性结直肠癌（HNPCC；林奇II）综合征。前两组与BRCA1和BRCA2肿瘤抑制基因的种系突变有关，而HNPCC与DNA错配修复（MMR）基因的种系突变有关，主要是hMLH1和hMSH2。所有上皮性卵巢癌中至少10%是遗传性的，BRCA基因突变约占病例的90%，其余10%中的大部分归因于HNPCC。与散发性癌症相比，遗传性卵巢癌表现出明显不同的临床病理特征。BRCA1突变携带者患卵巢癌的累积终生风险为40%至50%，BRCA2突变携带者为20%至30%。BRCA两种蛋白都参与基因表达的转录调控以及某些形式的DNA损伤，特别是双链断裂的识别或修复。BRCA1和BRCA2的突变主要是移码突变或无义突变。大多数与种系BRCA突变相关的卵巢癌在较年轻时被诊断出来，并且是高级别和晚期浆液性癌。BRCA突变似乎在黏液性或交界性卵巢肿瘤的发生中不起重要作用。与散发性癌症相比，遗传性卵巢癌的临床结局明显更好，化疗后的总生存期和无复发生存期更长。有家族史且包括2个或更多一级或二级亲属单独患有卵巢癌或同时患有乳腺癌和卵巢癌的女性，应在完成生育后立即进行预防性卵巢切除术，以降低患卵巢癌的风险。HNPCC家族中卵巢癌的累积风险超过12%。HNPCC综合征中的卵巢癌比一般人群中诊断得更早。大多数肿瘤是低分期的高分化或中分化癌。建议对这些患者进行年度随访。
