The diagnostic value of immunohistochemically detected methylthioadenosine phosphorylase deficiency in malignant pleural mesotheliomas

Histopathology. 2012 May;60(6B):E96-105. doi: 10.1111/j.1365-2559.2012.04196.x. Epub 2012 Mar 6.

Abstract

Aims: Malignant pleural mesothelioma (MPM) often causes diagnostic difficulties for pathologists. We assessed whether loss of methylthioadenosine phosphorylase (MTAP), a key enzyme in the intracellular recycling of adenosine triphosphate (ATP) often deleted in MPM, could be detected with immunohistochemistry (IHC) and used as a diagnostic marker for MPM.

Methods and results: We used IHC to detect MTAP in a cohort of 99 MPMs and 39 reactive mesothelial proliferations (RP) (reactive mesothelial hyperplasia n = 33, reactive pleural fibrosis n = 6). MTAP staining was assessed by an H score. The median H score of the RP cohort was set as a reference point. Cases with H scores below this reference point were considered to have decreased MTAP expression. We found that 64 of 99 (65%) of the investigated MPMs had decreased MTAP expression, while this was only true for nine of 39 (23%) of the RPs (P = 0.001). We further evaluated MTAP expression in a cohort of coagulated pleural effusions from 14 patients with MPM and 20 patients with RP by using a double-staining technique with Wilms tumour 1 (WT1) as a mesothelial marker. In these samples, decreased MTAP expression diagnosed MPM with a sensitivity of 71% and a specificity of 90%.

Conclusions: Decreased MTAP expression could potentially be useful in combination with other markers in the diagnosis of MPM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Humans
  • Immunohistochemistry
  • Mesothelioma / diagnosis*
  • Mesothelioma / metabolism
  • Mesothelioma / pathology
  • Pleural Neoplasms / diagnosis*
  • Pleural Neoplasms / metabolism
  • Pleural Neoplasms / pathology
  • Purine-Nucleoside Phosphorylase / deficiency
  • Purine-Nucleoside Phosphorylase / genetics*
  • Purine-Nucleoside Phosphorylase / metabolism

Substances

  • Biomarkers, Tumor
  • Purine-Nucleoside Phosphorylase
  • 5'-methylthioadenosine phosphorylase