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Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
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Correlation of methylthioadenosine phosphorylase (MTAP) protein expression with MTAP and CDKN2A copy number in

David B Chapel1, Adrian M Dubuc1, Jason L Hornick1

  • 1Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Histopathology
|January 2, 2021
PubMed
Abstract

Insights

Methylthioadenosine phosphorylase (MTAP) loss is common in malignant mesothelioma due to frequent co-deletion with CDKN2A. However, MTAP immunohistochemistry is only moderately sensitive for detecting this deletion.

Area of Science:

  • Oncology
  • Molecular Pathology
  • Cancer Genetics

Background:

  • Methylthioadenosine phosphorylase (MTAP) immunohistochemical expression is a known marker for CDKN2A deletion in malignant mesothelioma.
  • The correlation between MTAP expression and MTAP copy number in this cancer type has not been previously investigated.

Purpose of the Study:

  • To investigate the relationship between MTAP copy number and its immunohistochemical expression in malignant pleural mesothelioma.
  • To assess the utility of MTAP immunohistochemistry as a surrogate marker for CDKN2A deletion.

Main Methods:

  • Analysis of 40 malignant pleural mesothelioma tumors using targeted next-generation sequencing and/or single-nucleotide polymorphism microarray.
  • Correlation of MTAP and CDKN2A copy numbers with MTAP protein expression via immunohistochemistry.

Main Results:

  • CDKN2A deletion was observed in 68% of tumors, with MTAP codeletion in 74% of those cases.
  • Loss of MTAP expression occurred in 40% of tumors and was highly specific (95%) for MTAP deletion, but only moderately sensitive (59%) for CDKN2A deletion.
  • Heterogeneous MTAP staining was present in 23% of tumors, and the extent of MTAP loss correlated with molecularly detected MTAP deletion.

Conclusions:

  • MTAP is frequently codeleted with CDKN2A in pleural mesothelioma, though homozygous deletion is less common.
  • CDKN2A deletion often occurs with heterozygous MTAP deletion or normal MTAP copy number, leading to inconsistent MTAP expression.
  • MTAP immunohistochemistry is a highly specific but only moderately sensitive marker for detecting CDKN2A deletion in malignant mesothelioma.
Keywords:
cytogeneticshigh-throughput nucleotide sequencingimmunohistochemistrymesothelioma

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