MTAP-ing into mesothelioma diagnostics

admin May 8, 2012

Proteintech’s anti-MTAP antibody (11475-1-AP) has appeared in several research papers detailing the potential diagnostic value of the methylthioadenosine phosphorylase (MTAP) protein. The latest paper to feature our MTAP antibody was published in Histopathology this month and describes the diagnostic value of detecting MTAP in a subset of mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive malignant growth of the mesothelium that lines the pleural cavity. It is often a diagnostic minefield for pathologists due to other thoracic malignancies, but even more so because of benign pleural diseases which can mimic MPM.

These benign mesothelial cell proliferations can imitate malignancy due to high cell density and atypical appearance, and are considered ‘reactive proliferations’ (RPs). Conversely, some MPMs can appear morphologically benign.

Researchers in the Department of Pathology at the University Hospital of Copenhagen, Denmark, are trying to identify novel protein markers for MPM to better aid pathologists in their identification of this often indistinct disease.

Previous independent research had shown that the MTAP gene was deleted in 12 of 13 cytological MPM specimens; in contrast, none of 19 benign cytological samples were found to have MTAP deleted.

Immunohistochemistry of paraffin-embedded colon cancer using Proteintech anti-MTAP antibody 11475-1-AP (viewed using 10x lens).

The Copenhagen-based researchers then built on the above study, using IHC to detect MTAP in 99 MPM samples with the Proteintech 11475-1-AP MTAP antibody; they compared these with those of 39 benign RP cases using the median MTAP levels of the latter to set a threshold for healthy MTAP expression.

First author Zarah Glad Zimling and supervisors Anne Jørgensen and Eric Santoni-Rugiu found that 65% of the MPM samples investigated showed decreased MTAP expression, whereas only 23% of control RP sample showed any sort of reduction in this protein.

The researchers further evaluated MTAP expression in a cohort of pleural effusion samples from 14 MPM patients and 20 patients with RP. For these experiments, the team utilized a double-staining technique with Wilms tumour 1 (WT1) as positive marker for mesothelioma. In these samples, decreased MTAP expression diagnosed MPM with a sensitivity of 71% and a specificity of 90%.

In conclusion the researchers proffer that assessing the presence of MTAP – strictly in combination with several other potential markers - in suspected cases of MPM might be useful for diagnosing malignancy.

Related antibodies

MTAP rabbit polyclonal antibody

WT1 rabbit polyclonal antibody

Related publications

Zimling ZG, Jørgensen A and Santoni-Rugiu E, The diagnostic value of immunohistochemically detected methylthioadenosine phosphorylase deficiency in malignant pleural mesotheliomas, Histopathology (May 2012);60(6B):E96-E105.

Kim J, Kim MA, Min SY et al., Downregulation of methylthioadenosin phosphorylase by homozygous deletion in gastric carcinoma, Genes Chromosomes & Cancer (June 2011) ;50(6):421-33.

Sommer J, Itani DM, Homlar KC et al., Methylthioadenosine phosphorylase and activated insulin-like growth factor-1 receptor/insulin receptor: potential therapeutic targets in chordoma, J Pathol. (Apr 2010);220(5)608-17.

Huang HY, Li SH, Yu SC, et al., Homozygous deletion of MTAP gene as a poor prognosticator in gastrointestinal stromal tumors, Clin Cancer Res (November 2009);1515(22)6963-72.