Immunohistochemical Evaluation of BAP1 Expression in Breast Cancer with Known BRCA1 and BRCA2 Mutations and Comparison with Histopathological Features

Int J Surg Pathol. 2022 Jun;30(4):397-404. doi: 10.1177/10668969221085969. Epub 2022 Mar 9.

Abstract

Introduction. BRCA-mutated breast cancers have specific pathological characteristics. BAP1 is a tumor suppressor gene that is important in many cancers with different pathways. The relationship between BRCA1 mutation and BAP1 immunohistochemical staining is still unclear. Our aim is to determine whether BAP1 immunohistochemical expression indicates BRCA mutation status in breast carcinomas with specific pathological characteristics. In addition, we aim to determine the histopathological characteristics of tumors according to BRCA mutations. Methods. Histomorphology, molecular subtypes and BAP1 immunohistochemical expression patterns of the BRCA1/BRCA2 mutated and non-mutated tumors were evaluated. The BAP1 immunohistochemical stain was applied to nine tumor tissues with the BRCA1 mutation, six tumor tissues with the BRCA2 mutation, and 16 tumor tissues without any BRCA mutation. Pearson's chi square test and the Fisher Freeman Halton test were used to analyze the associations between the datas. The statistical significance was considered as P value of <.05. Results. Immunohistochemical BAP1 loss was not detected in any mutated or non-mutated tumor group. BRCA1 mutated tumors had the statistically highest histopathological grade (P = .04) and BRCA1/2 mutated tumors had significant immunohistochemical triple negative expression pattern (P = .01). Conclusions. Intrinsic and histopathological characteristics may vary between BRCA1 mutated and non-BRCA1 mutated tumors. Also, BAP1 loss was not detected in BRCA mutated breast tumors because of several effects of BAP1 that are non-related with BRCA in the cell cycle.

Keywords: BAP1; BRCA1; BRCA2; breast; cancer.

MeSH terms

  • BRCA1 Protein* / genetics
  • BRCA2 Protein* / genetics
  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Female
  • Genes, BRCA2
  • Humans
  • Mutation
  • Tumor Suppressor Proteins* / genetics
  • Ubiquitin Thiolesterase* / genetics

Substances

  • BAP1 protein, human
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase