Lax S F
Institut für Pathologie, LKH Graz Süd-West, Standort West, Göstingerstrasse 22, 8020, Graz, Österreich.
Pathologe. 2017 May;38(3):149-155. doi: 10.1007/s00292-017-0298-5.
Hereditary breast and ovarian carcinomas are frequently caused by germline mutations of the BRCA1 and BRCA2 genes (BRCA1/2 syndromes) and are often less associated with other hereditary syndromes such as Li-Fraumeni and Peutz-Jeghers. The BRCA1/2 proteins have a special role in DNA repair. Therefore, loss of function due to mutation causes an accumulation of mutations in other genes and subsequent tumorigenesis at an early age. BRCA1/2 mutations are irregularly distributed over the length of the genes without hot spots, although special mutations are known. Breast and ovarian cancer occur far more frequently in women with BRCA1/2 germline mutations compared with the general population. Breast cancer occurs increasingly from the age of 30, ovarian cancer in BRCA1 syndrome from the age of 40 and BRCA2 from the age of 50. Suspicion of a BRCA syndrome should be prompted in the case of clustering of breast cancer in 1st degree relatives, in particular at a young age, if breast and ovarian cancer have occurred, and if cases of male breast cancer are known. Breast carcinomas with medullary differentiation seem to predominate in BRCA syndromes, but other carcinoma types may also occur. BRCA germline mutations seem to occur frequently in triple-negative breast carcinomas, whereas an association with ductal carcinoma in situ (DCIS) is rare. Ovarian carcinomas in BRCA syndromes are usually high-grade serous, mucinous carcinomas and borderline tumors are unusual. Pathology plays a special role within the multidisciplinary team in the recognition of patients with hereditary cancer syndromes.
遗传性乳腺癌和卵巢癌通常由BRCA1和BRCA2基因的种系突变引起(BRCA1/2综合征),且通常与其他遗传性综合征如李-佛美尼综合征和黑斑息肉综合征关联较少。BRCA1/2蛋白在DNA修复中起特殊作用。因此,突变导致的功能丧失会引起其他基因的突变积累,并随后在早年发生肿瘤形成。BRCA1/2突变在基因长度上分布不规则,没有热点,尽管已知有特殊突变。与普通人群相比,携带BRCA1/2种系突变的女性患乳腺癌和卵巢癌的频率要高得多。乳腺癌发病年龄从30岁起逐渐增加,BRCA1综合征患者的卵巢癌发病年龄从40岁起,BRCA2综合征患者从50岁起。如果一级亲属中存在乳腺癌聚集现象,特别是在年轻时,如果同时发生乳腺癌和卵巢癌,以及如果已知有男性乳腺癌病例,就应怀疑存在BRCA综合征。在BRCA综合征中,具有髓样分化的乳腺癌似乎占主导,但也可能出现其他癌型。BRCA种系突变似乎在三阴性乳腺癌中频繁出现,而与导管原位癌(DCIS)的关联则很少见。BRCA综合征中的卵巢癌通常为高级别浆液性癌,黏液性癌和交界性肿瘤不常见。在多学科团队中,病理学在识别遗传性癌症综合征患者方面起着特殊作用。