Mammary analogue secretory carcinoma (MASC) is a recently described low-grade carcinoma with morphologic and genetic similarity, including ETV6-NTRK3 fusion, to secretory carcinoma of the breast. ETV6 is frequently involved in other epithelial and nonepithelial tumors, and many fusion partners of ETV6 have been reported. In the present study, 14 Japanese MASC cases were clinicopathologically and molecularly analyzed. The median age of the patients was 39 years, and the male:female ratio was 6:8. All cases showed histopathologic findings compatible with those previously described for MASC and harbored an ETV6 split as visualized by fluorescence in situ hybridization. Two cases showed thick fibrous septa and invasive features including vascular or perineural tumor involvement, findings that are rare in MASC. In addition, in these 2 cases, non-NTRK3 genes appeared to fuse with ETV6 (ETV6-X fusion). NTRK1 and NTRK2, both members of the NTRK family, were not involved. Of the 14 MASC cases, the ETV6-NTRK3 fusion transcript was positive in 6 cases, and the relative expression level of the ETV6-NTRK3 fusion transcript was variable, ranging from 1 to 5.8. Results of the present study of MASC suggest that (1) ETV6 occasionally fuses with unknown non-NTRK3 genes, (2) ETV6-X cases might have an invasive histology, (3) for molecular diagnosis of MASC, fluorescence in situ hybridization to detect ETV6 splits is the method of choice, and (4) the expression level of the ETV6-NTRK3 fusion transcript is considerably variable. These findings provide a novel insight into the oncogenesis, histopathology, diagnosis, treatment, and prognosis of this newly recognized carcinoma.
类似于乳腺分泌性癌的涎腺肿瘤(MASC)是最近描述的一种低级别癌，形态学和遗传学类似于乳腺分泌性癌，包括具有ETV6-NTRK3基因融合。ETV6易位常见于其它上皮性和非上皮性肿瘤，已经报道过许多ETV6融合方式。本研究分析了14例日本MASC病例的临床病理和分子特点。患者中位年龄为39岁，男：女为6:8。所有病例组织病理学表现均与文献中描述的MASC相似，FISH检测显示ETV6易位。其中2例组织学见厚的纤维分隔和浸润性特征，后者包括血管或神经周围侵犯，这些现象在MASC中少见。另外，这2例中，ETV6与非NTRK3基因发生融合(ETV6-X融合)。NTRK家族的两个成员NTRK1和NTRK2也与此无关。14例MASC病例中，有6例ETV6-NTRK3融合转录阳性，ETV6-NTRK3融合转录的表达水平变化不一，范围为1-5.8。本研究结果提示：(1) ETV6偶尔与未知的非NTRK3基因融合，(2) 发生ETV6-X融合的MASC病例组织学可能表现为浸润性，(3)MASC的分子诊断，应选择应用FISH法检测ETV6易位，(4)ETV6-NTRK3融合转录的表达水平变化范围很大。这些发现为MASC这一新型肿瘤的肿瘤发生、组织病理学、疾病诊断、治疗和预后提供了新见解。