Borg A, Isola J, Chen J, Rubio C, Johansson U, Werelius B, Lindblom A
Department of Oncology, University Hospital, Lund, Sweden.
Int J Cancer. 2000 Mar 15;85(6):796-800. doi: 10.1002/(sici)1097-0215(20000315)85:6<796::aid-ijc10>3.0.co;2-l.
Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease, predisposing to the development of colorectal cancer and other tumor types such as endometrial, small bowel, stomach, ovary and urinary tract carcinoma, while most investigators find no association between HNPCC and cancer of the breast. We have identified hMLH1 mutations in 2 Amsterdam-criteria HNPCC families where both male and female gene carriers were affected with breast cancer. To investigate whether these breast cancers were caused by other genetic factors, we analyzed the 2 breast cancer susceptibility genes BRCA1 and BRCA2. In one family we did not find any mutation in the breast cancer genes, while in the other, a BRCA1 mutation segregated in the breast cancer cases. Hereditary breast cancer, and in particular BRCA1 tumors, display discrete histo-pathological and immunohistological characteristics. The tumor from a woman with both hMLH1 mutations and a BRCA1 mutation exhibited typical BRCA1 histology, e.g., grade 3 invasive ductal carcinoma with dense lymphocytic infiltration, and immunohistology, estrogen receptor (ER) negative, progesterone receptor (PgR) negative, strongly p53 positive, c-erbB-2 negative and highly Ki67 positive (>50% stained cells). The histology of the breast tumor from the man with both one hMLH1 mutation and a BRCA1 mutation was a grade 2 invasive ductal carcinoma without any special BRCA1 features. Immunohistology was also different. This might merely reflect a true difference in male breast tumor progression vs. female. We cannot exclude that the combined effect of BRCA1 and hMLH1 dysfunction has a bearing on tumor progression.
遗传性非息肉病性结直肠癌（HNPCC）是一种常染色体显性疾病，易引发结直肠癌以及其他肿瘤类型，如子宫内膜癌、小肠癌、胃癌、卵巢癌和尿路癌，而大多数研究人员发现HNPCC与乳腺癌之间并无关联。我们在2个符合阿姆斯特丹标准的HNPCC家族中发现了hMLH1突变，这两个家族中的男性和女性基因携带者均患有乳腺癌。为了研究这些乳腺癌是否由其他遗传因素引起，我们分析了2个乳腺癌易感基因BRCA1和BRCA2。在一个家族中，我们未在乳腺癌基因中发现任何突变，而在另一个家族中，BRCA1突变在乳腺癌病例中呈分离状态。遗传性乳腺癌，尤其是BRCA1肿瘤，具有独特的组织病理学和免疫组织学特征。一名同时具有hMLH1突变和BRCA1突变的女性所患肿瘤表现出典型的BRCA1组织学特征，例如3级浸润性导管癌伴密集淋巴细胞浸润，以及免疫组织学特征，雌激素受体（ER）阴性、孕激素受体（PgR）阴性、p53强阳性、c-erbB-2阴性且Ki67高度阳性（>50%的染色细胞）。一名同时具有一个hMLH1突变和BRCA1突变的男性所患乳腺肿瘤的组织学类型为2级浸润性导管癌，无任何特殊的BRCA1特征。免疫组织学结果也有所不同。这可能仅仅反映了男性乳腺肿瘤与女性乳腺肿瘤进展的真实差异。我们不能排除BRCA1和hMLH1功能障碍的联合作用对肿瘤进展有影响。
