title: The diagnostic value of immunohistochemically detected methylthioadenosine phosphorylase deficiency in malignant pleural mesotheliomas.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: Department of Pathology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark. zarah.zimling@rh.regionh.dk
authors.forename: Zarah Glad
authors.initials: ZG
authors.lastname: Zimling
authors.forename: Anne
authors.initials: A
authors.lastname: Jørgensen
authors.forename: Eric
authors.initials: E
authors.lastname: Santoni-Rugiu
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008654:Mesothelioma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D010997:Pleural Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase