In:
Archives of Pathology & Laboratory Medicine, Archives of Pathology and Laboratory Medicine, ( 2023-03-10)
Abstract:
Low-grade fibromatosis-like metaplastic carcinoma (FLMC) is a very rare subtype of triple-negative metaplastic (spindle cell) breast carcinoma. It is characterized by the proliferation of spindle cells closely resembling fibromatosis, which represents a benign fibroblastic/myofibroblastic breast proliferation. Unlike most triple-negative and basal-like breast cancers, FLMC has a very low potential for metastases, but demonstrates frequent local recurrences. Objective.— To genetically characterize FLMC. Design.— To this end, we analyzed 7 cases by targeted next-generation sequencing for 315 cancer-related genes and performed comparative microarray copy number analysis in 5 of these cases. Results.— All cases shared TERT alterations (6 patients with recurrent c.-124C & gt;T TERT promoter mutation and 1 patient with copy number gain encompassing the TERT locus), had oncogenic PIK3CA/PIK3R1 mutations (activation of the PI3K/AKT/mTOR pathway), and lacked mutations in TP53. TERT was overexpressed in all FLMCs. CDKN2A/B loss or mutation was observed in 4 of 7 cases (57%). Furthermore, tumors displayed chromosomal stability with only few copy number variations and a low tumor mutational burden. Conclusions— We conclude that FLMCs typically show the recurrent TERT promoter mutation c.-124C & gt;T, activation of the PI3K/AKT/mTOR pathway, low genomic instability, and wild-type TP53. In conjunction with previous data of metaplastic (spindle cell) carcinoma with and without fibromatosis-like morphology, FLMC is most likely distinguished by TERT promoter mutation. Thus, our data support the notion of a distinct subgroup within low-grade metaplastic breast cancer with spindle cell morphology and associated TERT mutations.
Type of Medium:
Online Resource
ISSN:
1543-2165
,
0003-9985
DOI:
10.5858/arpa.2022-0159-OA
Language:
English
Publisher:
Archives of Pathology and Laboratory Medicine
Publication Date:
2023
detail.hit.zdb_id:
2028916-9
