A new study has attempted to identify several biomarkers associated with metaplastic breast carcinoma (MBC), a highly aggressive form of triple-negative breast cancer (TNBC).
“Clinically, MBCs are more metastatic and chemoresistant than nonmetaplastic TNBC, with the spindle subtype reported to have the worst prognosis,” the researchers wrote. “This significant clinical challenge highlights the need to distinguish MBC tumors for diagnostic and precision treatment purposes.”
In order to explore this further, researchers used multiplex quantitative tandem mass tag-based proteomics and quantified 5798 proteins from 27 patients. Of these, 15 samples were from patients with MBC (6 spindle, 4 squamous, and 5 sarcomatoid subtypes); 6 were for nonmetaplastic TNBCs; and 6 were from normal adjacent breast tissues.
Some features associated with the MBC proteome compared with normal breast tissue included a global downregulation program “involving major tumor suppressors, extracellular matrix activities, and wound healing response.”
Compared with TNBC protein profiles, the MBC-specific samples had increases related to epithelial-to-mesenchymal transition and extracellular matrix, and reduced metabolic pathways. Additionally, MBC subtypes had “distinct upregulated profiles, including translation and ribosomal events in spindle, inflammation- and apical junction-related proteins in squamous and extracellular matrix proteins in sarcomatoid subtypes.”
Finally, whole-exome sequencing analyses comparing normal breast tissue with MBC tissue from the same patients identified somatic mutations common to all MBCs in TP53, MUC17, CRYBG2, PLEC, and ZNF681. All but TP53 are novel mutations in MBC.
“We found that while spindle and squamous MBC exhibit overlapping mutational profiles of genes involved in transcription, RNA metabolic processes and actin filament binding, sarcomatoid tumors harbor distinct mutations, especially in MAPK, WNT, protocadherin cluster genes, calcium binding, and ECM organization,” the researchers wrote. “Taken together, we discovered distinct somatic mutational profiles in MBC tumors, highlighting that of sarcomatoid MBC compared with the overlapping landscape of spindle and squamous tumors.”
Djomehri SI, Gonzalez ME, da Veiga Leprevost F, et al. Quantitative protecomic landscape of metaplastic breast carcinoma pathological subtypes and their relationship to triple-negative tumors. Nat Commun. 2020;11(1):1723.