From Cell Biology to Tissue Engineering


Expression of plakophilin 3 in diffuse malignant pleural mesothelioma

Silvija Mašić1, Luka Brčić2,3, Božo Krušlin1, Ana Šepac2, Biserka Pigac4, Dinko Stančić-Rokotov5, Marko Jakopović6 and Sven Seiwerth2,7

1Clinical Department of Pathology and Cytology "Ljudevit Jurak", Sestre Milosrdnice University Hospital Centre, 2Institute of Pathology, University of Zagreb, Zagreb, Croatia, 3Institute of Pathology, Medical University of Graz, Graz, Austria, 4Department of Pathology, Cytology and Forensic Medicine, Varaždin General Hospital, Varaždin, 5Department of Thoracic Surgery, University of Zagreb, 6Clinical Department of Pulmology, Clinical Hospital Centre Zagreb and 7Clinical Department of Pathology and Cytology, Clinical Hospital Centre Zagreb, Zagreb, Croatia

Offprint requests to: Silvija Mašić, MD, PhD, Clinical Department of Pathology and Cytology "Ljudevit Jurak", Sestre Milosrdnice University Hospital Centre, Vinogradska cesta 29, 10000 Zagreb, Croatia. e-mail: silvijamasic57@gmail.com

Summary. Diffuse malignant pleural mesothelioma (DMPM) is the most common primary malignant pleural neoplasm still posing major diagnostic, prognostic and therapeutic challenges. Plakophilins are structural proteins considered to be important for cell stability and adhesion in both tumor and normal tissues. Plakophilin 3 is a protein present in desmosomes of stratified and simple epithelia of normal tissues with presence in malignant cells of various tumors where it participates in the process of tumorigenesis. The aim of this study was to investigate the expression of plakophilin 3 protein in DMPM, but also to study its prognostic significance and relation to histologically accessible parameters of aggressive growth. Archival samples of tissue with established diagnosis of DMPM and samples of normal pleural tissue were used. Tumor samples were classified into three histological types of DMPM (epithelioid, sarcomatoid and biphasic). Additional subclassification of epithelioid mesotheliomas into nine patterns based on the prevalent histological component of the tumor was then performed. After immunohistochemical staining, cytoplasmic and membrane immunopositivity of tumor cells was assesed by scoring the intensity of the staining from 0 (no staining) to 4 (very strong staining). Prognostic value and expression of plakophilin 3 with consideration to histologically estimated aggression in tumor growth were then statistically analyzed using non- parametric tests. The results demonstrated higher level of plakophilin 3 expression in tumor samples with histologically more aggressive tumor growth, but no significant prognostic value. According to our study, plakophilin 3 appears to be involved in tumor invasion in malignant mesothelioma. Histol Histopathol 33, 995-1004 (2018)

Key words: Plakophilin 3, Diffuse malignant pleural mesothelioma, Invasiveness, Immunohistochemistry

DOI: 10.14670/HH-11-996