Gregory R Bean1, Gregor Krings2, Christopher N Otis3, David A Solomon2, Joaquín J García4, Annemieke van Zante2, Sandra Camelo-Piragua5, Jessica van Ziffle2, Yunn-Yi Chen2. 1. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. 2. Department of Pathology, University of California San Francisco (UCSF), San Francisco, CA, USA. 3. Department of Pathology, Baystate Medical Center (University of Massachusetts Medical School-Baystate), Springfield, MA, USA. 4. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 5. Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Abstract
AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.
AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.
Authors: Fresia Pareja; Arnaud Da Cruz Paula; Rodrigo Gularte-Mérida; Mahsa Vahdatinia; Anqi Li; Felipe C Geyer; Edaise M da Silva; Gouri Nanjangud; Hannah Y Wen; Zsuzsanna Varga; Edi Brogi; Emad A Rakha; Britta Weigelt; Jorge S Reis-Filho Journal: NPJ Breast Cancer Date: 2020-06-05
Authors: Fresia Pareja; Arnaud Da Cruz Paula; Rodrigo Gularte-Mérida; Mahsa Vahdatinia; Anqi Li; Felipe C Geyer; Edaise M da Silva; Gouri Nanjangud; Hannah Y Wen; Zsuzsanna Varga; Edi Brogi; Emad A Rakha; Britta Weigelt; Jorge S Reis-Filho Journal: NPJ Breast Cancer Date: 2020-06-05