Abstract 29P
Background
Mucoepidermoid carcinoma (MEC) of the breast is an extremely rare form of salivary gland-type tumor morphologically characterized by four types of cells (basaloid, intermediate, epidermoid, and mucinous) arranged in solid and cystic patterns. Despite its triple-negative phenotype, breast MECs are reported to have a relatively good clinical behavior. However, no data on their biology and therefore no guidelines for their clinical management are currently available. Here, we sought to characterize the molecular landscape of breast MECs.
Methods
Thirteen cases were included and histologically reviewed. Tumor infiltrating lymphocytes (TILs), along with the immunohistochemical expression of programmed death ligand 1 (PD-L1, clone 22C3), EGFR, and amphiregulin (AREG) were assessed. The presence of MAML2 and EWSR1 rearrangements was investigated by fluorescent in situ hybridization. Eight cases with available enough tissue material were subjected to a next-generation sequencing (NGS) panel targeting 161 cancer-related genes.
Results
Most cases were of low histological grade (n=10, 77%) with low proliferation (Ki67<30%). TILs were found in 2 (17%) cases, while PD-L1 combined positive score ranged from 0 to 20 (median 12.5). All cases showed EGFR overexpression and 2 of them were AREG-positive, among which one patient developed metastasis. No MAML2 or EWSR1 rearrangements were detected. Pathogenic mutations in PIK3CA were highly recurrent (n=4/8; 50%), though only one case harbored TP53 mutations. Additional somatic mutations affecting cancer-related genes found in MECs included CDK2, NF1/2, AKT1, SMARCB1, MYC, KRAS, CDK4, NOTCH1, and FGFR3/4.
Conclusions
This is the first study providing molecular data on breast MECs and the broadest collection of cases presented so far. Here we show that breast MECs lack the hallmark TP53 mutation found in high-grade forms of TNBC but also the MAML2 or EWSR1 rearrangements found in salivary MECs. The low level of TILs and PD-L1 suggest an immunoediting deficiency and that MECs may be unlikely to respond to immunotherapy combination strategies. Finally, the EGFR-AREG axis activation, coupled with the complex patterns of mutations in PI3K/AKT/mTOR and cell cycle regulation pathways warrant caution in considering MECs as low-grade TNBCs.
Legal entity responsible for the study
The authors.
Funding
Italian ministry of health (Ricerca Corrente Funds).
Disclosure
All authors have declared no conflicts of interest.