Diagnostic utility of MTAP, Merlin and RBFOX1 immunohistochemistry in mesothelial proliferations
Project no. 33159 · Status: Kapanmış (Yayın bekleniyor) · 2025
Summary
<p><span style="color: rgb(0, 0, 0);">Pleural mesothelioma (PM) is a rare but highly aggressive malignancy characterized by significant heterogeneity at both morphological and molecular levels, leading to diagnostic difficulties and poor prognosis. The structural variations among epithelioid, sarcomatoid, and biphasic subtypes, their histological resemblance to reactive mesothelial proliferations, and the limited sampling in small biopsies restrict the diagnostic sensitivity of currently available immunohistochemical (IHC) markers. Although molecular alterations such as p16 (CDKN2A) deletion guide PM diagnosis, these markers lack sufficient diagnostic power in all cases, and molecular methods are required to detect p16 deletion. In recent years, the immunohistochemical loss of expression of the MTAP protein, located in the same chromosomal region as p16, has emerged as an important diagnostic marker. Furthermore, the loss of Merlin due to NF2 mutations, which are common in PM, is critical for both diagnosis and the biological behavior of the mesothelioma. Additionally, structural alterations associated with mesothelioma have been demonstrated in the RBFOX1 (A2BP1) gene, making this gene a new diagnostic candidate; however, its expression at the protein level via IHC has not yet been evaluated in the literature. In this project, the diagnostic values of MTAP, Merlin, and RBFOX1 expressions, their relationship with histological subtypes, and the contribution of potential panel combinations were investigated by comparing PM and reactive mesothelial proliferations. In our study, slides from approximately 100 adult (>18 years old) cases with histopathologically and clinically confirmed PM and approximately 50 excised cases diagnosed with reactive mesothelial proliferation (chronic fibrous pleuritis, atypical mesothelial hyperplasia) were evaluated. IHC staining was performed for all three markers, followed by scoring and statistical analysis. Consequently, we aimed to contribute to the development of more specific, sensitive, and reliable immunohistochemical panels for PM, which inherently causes diagnostic challenges.</span></p>