Malignant mesothelioma (MM) is a rare type of malignancy. The main risk factor for mesothelioma is exposure to asbestos, which is readily available in the occupational environment [1]. Although it is very important to distinguish MM from reactive mesothelial proliferation (RMP), morphological differentiation may sometimes be challenging [2,3]. Several new adjunctive techniques have been developed that can help differentiate MM from RMP, including immunohistochemical staining for BRCA1-associated protein 1 (BAP1), methylthioadenosine phosphorylase (MTAP) and 5-hydroxymethyl cytosine, cyclin-dependent kinase inhibitor 2 A (CDKN2A) and NF2 fluorescence in situ hybridization (FISH), but each assay has several drawbacks [3]. These tests are used specifically to diagnose malignancies, but none of them has a sensitivity rate close to 100 %, even when used in combination [4]. Therefore, further studies should be conducted to find diagnostic biomarkers with higher specificity, sensitivity and accuracy to differentiate MM from RMP.

The Hippo pathway is a signaling kinase cascade involved in the control of apoptosis, stress responses and cell proliferation. If the Hippo pathway becomes dysfunctional due to mutations/deletions of its various components, uncontrolled transport of YAP/TAZ complex into the nucleus, followed by activation of various genes that affect cell proliferation becomes manifest. One of the downstream effects of YAP/TAZ signaling pathway is increased cyclin D1 transcription [5]. Cyclin D1 is overexpressed and/or amplified in the majority of human cancers. Pancreatic cancer, non-small cell lung cancer, breast cancer and squamous cell carcinomas of the head and neck are types of malignancies with frequent cyclin D1 genomic alterations. Clinicopathological studies have shown that overexpression of cyclin D1 is associated with tumor metastasis and poor prognosis in some cancer types [6]. Genomic abnormalities related to Hippo pathway are present in numerous types of malignancies [5]. Mutations/deletions of components of the Hippo pathway are frequently seen in cases with malignant mesotheliomas [3].

RMP usually does not require further treatment, whereas MM has a poor prognosis. It is therefore particularly important that any ancillary test should have a very high specificity for MM [2]. Although diagnostic accuracy has improved with the launching of new immunohistochemical and molecular markers used to differentiate MM from RMP, there is still a need to investigate new biomarkers.

The aim of this study is to examine the potential role of cyclin D1 immunostaining in differentiating MM from RMP.