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

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.

• Authors: Zarah Glad Zimling, Anne Jørgensen, Eric Santoni-Rugiu
• Journal: Histopathology (Histopathology) Vol. 60 Issue 6B Pg. E96-105 (May 2012) ISSN: 1365-2559 [Electronic] England
• PMID: 22394205 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

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

Topics

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