Sarcomatoid Mesothelioma: A CDKN2A molecular analysis of 53 cases with immunohistochemical correlation with BAP1

Pathol Res Pract. 2020 Dec;216(12):153267. doi: 10.1016/j.prp.2020.153267. Epub 2020 Nov 2.

Abstract

Fifty-three cases of sarcomatoid pleural mesothelioma were evaluated for CDKN2A (p16) homozygous deletion and correlated with BRCA-associated protein-1 (BAP1) expression by immunohistochemistry. The patients are 45 men and 8 women between the ages of 37 and 79 years (average age: 58 years), who presented with symptoms of chest pain, cough, and weight loss. Diagnostic imaging showed the presence of diffuse pleural thickening with encasement of the lung parenchyma in all the cases. All patients were surgically treated with extrapleural pneumonectomy. Loss of BAP1 reactivity was seen in 49 tumors and p16 homozygous deletion was seen in 41 tumors, while in 16 patients either BAP1 or p16 were noncontributory to the diagnosis of mesothelioma. However, we were able to detect a better survival rate in those patients in whom BAP1 was lost and p16 showed homozygous deletion. Our findings showed that even though the use of BAP1 and p16 are important tools in the diagnosis of mesothelioma, a proportion of cases still remains negative with approximately 30 % of the cases in which the concordance of BAP1 loss and p16 homozygous deletion will not be present. We consider that the final diagnosis of mesothelioma is best accomplished by a global interpretation of clinical, radiographic, and pathological features including immunohistochemistry and molecular studies.

Keywords: BAP-1; Mesothelioma; Pleura; Sarcomatous; p16.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Female
  • Gene Deletion*
  • Homozygote
  • Humans
  • Immunohistochemistry*
  • In Situ Hybridization, Fluorescence*
  • Male
  • Mesothelioma, Malignant / chemistry
  • Mesothelioma, Malignant / genetics*
  • Mesothelioma, Malignant / pathology
  • Mesothelioma, Malignant / surgery
  • Middle Aged
  • Pleural Neoplasms / chemistry
  • Pleural Neoplasms / genetics*
  • Pleural Neoplasms / pathology
  • Pleural Neoplasms / surgery
  • Predictive Value of Tests
  • Sarcoma / chemistry
  • Sarcoma / genetics*
  • Sarcoma / pathology
  • Sarcoma / surgery
  • Treatment Outcome
  • Tumor Suppressor Proteins / analysis*
  • Ubiquitin Thiolesterase / analysis*

Substances

  • BAP1 protein, human
  • Biomarkers, Tumor
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase