Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Pathology, University of California San Francisco (UCSF), San Francisco, CA, USA.
Histopathology. 2019 Feb;74(3):463-473. doi: 10.1111/his.13779. Epub 2018 Dec 5.
Mucoepidermoid carcinomas (MEC) are the most common malignant neoplasms of salivary glands, but are uncommon in other sites. Salivary gland MEC are most frequently associated with CRTC1-MAML2 translocations. Exceedingly rare MEC of the breast demonstrate a basal-like and often triple (oestrogen and progesterone receptor, HER2)-negative immunophenotype, with a single case previously reported to show MAML2 rearrangement, although the fusion partner was not known. Comprehensive genomic studies of breast MEC are lacking. In this study, we analysed the immunophenotype and molecular landscape of two breast MEC to elucidate the pathogenesis of these rare tumours.
Two breast MEC were subjected to capture-based next-generation DNA sequencing of 479 cancer-related genes. The presence of the CRTC1-MAML2 fusion transcript was interrogated by reverse transcriptase-polymerase chain reaction. In addition, the immunoprofiles of breast MEC were compared to salivary gland MEC. Both breast MEC harboured CRTC1-MAML2 fusions. In contrast to most triple-negative breast carcinomas of no special type, the mutational burden of MEC was very low, with one case demonstrating only an inactivating SETD2 mutation, and the other harbouring no somatic variants in genes on the panel. No copy number alterations were identified. The immunoprofiles of breast and salivary gland MEC were overlapping, but not identical.
The findings highlight MEC as a breast cancer subtype more closely related to its salivary gland counterpart than to basal-like/triple-negative breast cancers of no special type.
黏液表皮样癌（MEC）是唾液腺最常见的恶性肿瘤，但在其他部位并不常见。唾液腺 MEC 最常与 CRTC1-MAML2 易位相关。乳腺 MEC 极为罕见，表现为基底样，且常为三阴性（雌激素受体、孕激素受体和 HER2），既往仅报道过一例存在 MAML2 重排，但融合伙伴未知。乳腺 MEC 的全面基因组研究尚缺乏。本研究通过对 479 个与癌症相关基因的捕获二代测序，分析了两例乳腺 MEC 的免疫表型和分子特征，以阐明这些罕见肿瘤的发病机制。
对两例乳腺 MEC 进行了 479 个与癌症相关基因的捕获二代测序。通过逆转录聚合酶链反应检测 CRTC1-MAML2 融合转录本的存在。此外，还比较了乳腺 MEC 的免疫表型与唾液腺 MEC。两例乳腺 MEC 均存在 CRTC1-MAML2 融合。与大多数非特殊类型的三阴性乳腺癌不同，MEC 的突变负担非常低，一例仅存在失活的 SETD2 突变，另一例在该基因面板中未发现体细胞变异。未发现拷贝数改变。乳腺和唾液腺 MEC 的免疫表型重叠，但不完全相同。
这些发现强调了 MEC 作为一种乳腺癌亚型，与唾液腺来源的 MEC 更为相关，而与非特殊类型的基底样/三阴性乳腺癌关系较远。
