Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
BMC Cancer. 2013 Feb 1;13:46. doi: 10.1186/1471-2407-13-46.
Acinic cell carcinoma (ACC) is a rare malignant epithelial neoplasm characterized by the presence of malignant tubular acinar exocrine gland structures. Diagnosis is generally made in salivary glands and in the pancreas. ACC of the breast has been reported in few cases only. Carriers of inherited mutations in the BRCA1 gene are prone to the development of breast cancer, mainly invasive ductal or medullary type carcinomas. We describe for the first time a BRCA1 mutation carrier with a diagnosis of ACC of the breast.
The patient developed an invasive ductal carcinoma (IDC) at the age of 40 years and an ACC in the contralateral breast at 44 years. Immunohistochemical examination of the ACC revealed a triple negative status (i.e., negativity for estrogen receptor, progesterone receptor and HER2 protein) and positivity for p53. Using a combination of loss of heterozygosity (LOH) and sequencing analyses, the loss of the wild-type BRCA1 allele was detected in both the ACC and the IDC. In addition, two different somatic TP53 mutations, one in the ACC only and another one in the IDC only, were observed.
Both the immunohistochemical and molecular features observed in the ACC are typical of BRCA1-associated breast cancers and suggest an involvement of the patient's germline mutation in the disease. The occurrence of rare histological types of breast cancers, including malignant phyllodes tumor, atypical medullary carcinoma and metaplastic carcinoma, in BRCA1 mutation carriers has been already reported. Our findings further broaden the spectrum of BRCA1-associated breast malignancies.
涎腺和胰腺中常发生腺样囊性癌（ACC），这是一种罕见的恶性上皮性肿瘤，其特征是存在恶性管状腺外分泌腺结构。乳腺癌中仅报道过少数 ACC 病例。BRCA1 基因突变携带者易患乳腺癌，主要为浸润性导管癌或髓样癌。我们首次描述了一名 BRCA1 基因突变携带者患有乳腺癌 ACC。
患者 40 岁时发生浸润性导管癌（IDC），44 岁时对侧乳房发生 ACC。ACC 的免疫组织化学检查显示三阴性状态（即雌激素受体、孕激素受体和 HER2 蛋白均为阴性）和 p53 阳性。通过杂合性缺失（LOH）和测序分析的组合，在 ACC 和 IDC 中均检测到野生型 BRCA1 等位基因的丢失。此外，还观察到两种不同的体细胞 TP53 突变，一种仅在 ACC 中，另一种仅在 IDC 中。
ACC 中观察到的免疫组织化学和分子特征均为 BRCA1 相关乳腺癌的典型特征，提示患者的种系突变参与了该疾病。BRCA1 基因突变携带者中已经报道了罕见的乳腺癌组织学类型，包括恶性叶状肿瘤、非典型髓样癌和间变性癌。我们的发现进一步拓宽了 BRCA1 相关乳腺癌恶性肿瘤的范围。
