Low-grade fibromatosis-like spindle cell carcinomas of the breast are molecularly exiguous

J Clin Pathol. 2015 May;68(5):362-7. doi: 10.1136/jclinpath-2014-202824. Epub 2015 Feb 23.

Abstract

Background: Low-grade fibromatosis-like spindle cell carcinomas are very rare breast carcinomas comprising <0.5% of all breast cancers. They demonstrate immunohistochemical (IHC) features of basal-like/metaplastic breast carcinomas, but the underlying molecular characteristics are unknown. We hypothesised that, as with IHC similarities, there may be common genomic alterations between spindle cell and basal-like/metaplastic carcinomas.

Methods and results: Genomic mutational profile and genomic copy number aberration (CNA) analyses were performed on three cases of this unusual entity, and findings were compared with that reported for basal-like/metaplastic breast carcinomas. Copy number analyses by molecular inversion probe assays of the three spindle cell carcinoma samples revealed little overall genomic CNAs with only minor changes identified (fraction of the genome altered; 1.3%-6.4%), but with a common 9p21.3 loss in 2 out of 3 samples, with CDKN2A (p16) being a likely candidate. No areas of commonality were identified in an in silico analysis compared with publically available basal-like/metaplastic carcinoma copy number data.

Conclusions: These tumours are characterised by low genomic instability, and share no CNAs with other metaplastic carcinomas. These findings favour this entity being a unique group genotype and belie their apparent homogeneous morphology and phenotype.

Keywords: BREAST CANCER; CANCER GENETICS; HISTOPATHOLOGY.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Biopsy
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / classification
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma / chemistry
  • Carcinoma / classification
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Chromosomes, Human, Pair 9
  • Computer Simulation
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Databases, Genetic
  • Female
  • Fibroma / chemistry
  • Fibroma / classification
  • Fibroma / genetics*
  • Fibroma / pathology
  • Gene Dosage
  • Genes, p16
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Metaplasia
  • Mutation
  • Neoplasm Grading
  • Phenotype

Substances

  • Biomarkers, Tumor