Evaluation of SWI/SNF Protein Expression by Immunohistochemistry in Ovarian Clear Cell Carcinoma

Int J Gynecol Pathol. 2021 Mar 1;40(2):156-164. doi: 10.1097/PGP.0000000000000687.

Abstract

Ovarian clear cell carcinomas (OCCC) are known to harbor ARID1A mutations, and several recent studies have described immunohistochemical loss of SMARCA2, SMARCA4, and SMARCB1 in a subset of tumors. We performed ARID1A, SMARCA2, SMARCA4, and SMARCB1 immunohistochemistry on 105 OCCCs to identify possible associations with clinicopathologic features and assess their prognostic value in these tumors. ARID1A, SMARCA4, and SMARCB1 were considered retained if any tumor cell nucleus stained while for SMARCA2, >5% of tumor nuclei were required to be positive. Patients had a mean age of 56 yr and tumors averaged 13 cm in size. Most patients (63%) had stage I tumors with 47% being alive and well, 41% dead from disease, 10% dead from other causes, and 3% alive with disease at last follow-up (mean 72 mo). Tumors showed an admixture of architectural patterns, but papillary was most frequent (49%). Stromal hyalinization was detected in 83% of OCCCs and a background precursor in 78%. High-grade atypia and/or oxyphilic cells were noted in 45% and 29% of tumors, respectively. All OCCCs expressed SMARCA4 and SMARCB1, but the absence of ARID1A was noted in 30% of tumors and SMARCA2 in 8%. ARID1A-retained OCCCs were associated with a dominant tubulocystic or solid pattern, but no other clinicopathologic features reached statistical significance. No switch/sucrose non-fermentable protein expression was predictive of prognosis. Additional studies with known mutational status of these proteins are warranted to better assess their prognostic utility and develop a standardized immunohistochemical scoring system.

MeSH terms

  • Adenocarcinoma, Clear Cell / diagnosis
  • Adenocarcinoma, Clear Cell / genetics
  • Adenocarcinoma, Clear Cell / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • SMARCB1 Protein / genetics
  • SMARCB1 Protein / metabolism
  • Tissue Array Analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • ARID1A protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • SMARCA2 protein, human
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases