Prognostic Value of the Immunohistochemical Expression of RAD51 and BRCA2 in Gastric Adenocarcinoma

J Histochem Cytochem. 2022 Mar;70(3):199-210. doi: 10.1369/00221554211065834. Epub 2022 Jan 3.

Abstract

Current scientific literature lacks data on the prognostic value of the expression of RAD51 and BRCA2 in gastric adenocarcinoma. Therefore, we aimed to evaluate those and other homologous recombination-related proteins (ATM, ATR, BRCA1, CHK2, γH2AX, p53) in gastric cancer, assessing their correlation with clinical prognosis. Paraffin-embedded samples were obtained from surgical specimens collected in total or subtotal gastrectomy procedures. Between 2008 and 2017, 121 patients with advanced gastric adenocarcinoma underwent surgical resection and were included in this study. Negativity for nuclear RAD51 correlated with vascular invasion, lymph node metastasis, larger tumor size, and lower overall survival and disease-free survival in univariate analysis. However, nuclear RAD51-negative cases presented better response rates to adjuvant therapy than the positive ones. Nuclear ATR negativity correlated with larger tumor size and a higher histological grade. Positivity for ATM was associated with more prolonged disease-free survival. Positivity for nuclear BRCA2 correlated with lower overall survival and diffuse histological type, whereas its high expression was associated with vascular invasion. Nevertheless, tumors positive for nuclear BRCA2 were more frequently low grade in the intestinal histological type. Our findings indicate that RAD51 and BRCA2 are valuable immunohistochemical prognostic markers in gastric adenocarcinoma.

Keywords: DNA repair; homologous recombination; immunohistochemistry; stomach neoplasms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / metabolism
  • BRCA2 Protein / analysis*
  • BRCA2 Protein / biosynthesis
  • Cohort Studies
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prognosis
  • Rad51 Recombinase / analysis*
  • Rad51 Recombinase / biosynthesis
  • Retrospective Studies
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / metabolism

Substances

  • BRCA2 Protein
  • BRCA2 protein, human
  • RAD51 protein, human
  • Rad51 Recombinase