Identification of Novel Diagnostic Markers for Malignant Pleural Mesothelioma Using a Reverse Translational Approach Based on a Rare Synchronous Tumor.

Tomoaki Naka,Yutaka Hatanaka,Hiromi Okada,Vishwa Jeet Amatya,Kichizo Kaga,Yukiko Tabata,Akira Takasawa,Yasuhiro Hida,Hideo Akiyama,Kouki Inai,Yukio Takeshima,Yoshihiro Matsuno,Kei Kushitani,Kanako C Hatanaka,Tomoko Mitsuhashi

doi:10.3390/diagnostics12020316

Abstract

Although the routine use of immunohistochemistry has improved the accuracy of histopathologic diagnosis in clinical practice, new methods for discovering novel diagnostic markers are still needed. We sought new diagnostic markers for malignant pleural mesothelioma (MPM) using a reverse translational approach with limited archival tissues from a very rare case. Total RNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues of a synchronous collision tumor consisting of MPM and pulmonary adenocarcinoma (PAC) was employed for gene expression profiling (GEP) analysis. Among the 54 genes selected by GEP analysis, we finally identified the following two candidate MPM marker genes: PHGDH and TRIM29. Immunohistochemical analysis of 48 MM and 20 PAC cases showed that both PHGDH and TRIM29 had sensitivity and specificity almost equivalent to those of calretinin (sensitivity 50% and 46% vs. 63%, and specificity 95% and 100% vs. 100%, respectively). Importantly, of the 23 epithelioid MMs, all 3 calretinin-negative cases were positive for TRIM29. These two markers may be diagnostically useful for immunohistochemical distinction between MPMs and PACs. This successful reverse translational approach based on FFPE samples from one very rare case encourages the further use of such samples for the development of novel diagnostic markers.

Highlights

Malignant mesothelioma (MM) is a relatively rare disease, but the number of deaths from this disease has increased over the years [1]
Lower RNA integrity was observed in the pulmonary adenocarcinoma (PAC) than in the malignant pleural mesothelioma (MPM), gene expression profiling (GEP) analysis was successful for both lesions
We demonstrated that a reverse translational approach has great potential for the discovery of novel diagnostic markers, by focusing on a rare single case of collision tumor comprising two tumors that had arisen concurrently from two different types of cell

Summary

Introduction

Malignant mesothelioma (MM) is a relatively rare disease, but the number of deaths from this disease has increased over the years [1]. MM has a longer incubation period than other diseases, and the incubation period from the initial exposure to asbestos to the onset of MM is thought to be about 40 years on average [2,3]. Even in the present era, when the use of asbestos is banned, the number of deaths from MM in the world is estimated to continue to increase, and it is thought that the number of deaths will reach its peak in Japan, for example, from 2030 to 2034 [1]. Because of the limited treatment options, survival time and cost, MM is a major problem throughout the world [4].

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