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Micropapillary variant of mucinous carcinoma of the breast shows genetic alterations intermediate between those of mucinous carcinoma and micropapillary carcinoma
Author(s) -
Pareja Fresia,
Selenica Pier,
Brown David N,
Sebastiao Ana P M,
Silva Edaise M,
Da Cruz Paula Arnaud,
Del Angela,
Fu Li,
Weigelt Britta,
Brogi Edi,
ReisFilho Jorge S,
Wen Hannah Y
Publication year - 2019
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13853
Subject(s) - mucinous carcinoma , biology , pathology , carcinoma , breast cancer , breast carcinoma , somatic cell , cancer research , cancer , adenocarcinoma , gene , medicine , genetics
Aims Micropapillary variant of mucinous carcinoma of the breast ( MPMC ) is a rare histological form of oestrogen receptor ( ER )‐positive invasive carcinoma that is characterised by micropapillary clusters of tumour cells in lakes of extracellular mucin. The aims of this study were to determine the genetic alterations underpinning MPMC s, and to determine whether they overlap with those of mucinous carcinomas and/or invasive micropapillary carcinomas. Methods and results DNA from five MPMC s was subjected to whole‐exome sequencing. Somatic mutations, copy number alterations and mutational signatures were determined with state‐of‐the‐art bioinformatics methods. No mutations in genes significantly mutated in breast cancer, including TP 53 , PIK 3 CA , GATA 3 , and MAP 3K1 , were detected. We identified copy number alterations that have been reported in invasive micropapillary carcinomas, such as recurrent gains in 1q, 6p, 8q, and 10q, and recurrent losses in 16q, 11q, and 13q, as well as a recurrent 8p12–8p11.2 amplification encompassing FGFR 1 . Like mucinous carcinomas, three of the five MPMC s analysed lacked PIK 3 CA mutations, 1q gains, and 16q losses, which are the hallmark genetic alterations of ER ‐positive breast cancers, whereas two MPMC s harboured 16q losses and/or a complex pattern of copy number alterations similar to those found in breast‐invasive micropapillary carcinomas. Conclusions MPMC s are heterogeneous at the genetic level; some tumours show a pattern of somatic genetic alterations similar to those of mucinous carcinomas, whereas others resemble invasive micropapillary carcinomas at the genetic level. These findings suggest that MPMC s may not constitute one histological subtype, but rather a convergent phenotype that can stem from mucinous carcinomas or invasive micropapillary carcinomas.