Molecular evaluation of WNT and EGFR pathways in primary pleural cancers

Malignant Pleural Mesothelioma (MPM) and Pleural Synovial Sarcoma (PSS) are rare and aggressive pleural cancers. Compared to MPM, PSS occur more often in youth, although both forms are united by a poor prognosis. Wnt/b-catenin and EGFR signaling play key roles in embryonic development, in the determination of cell fate, tissues stem cell renewal and homeostasis. It is well documented that dysregulation of these pathways leads to tumorigenesis with poor prognosis but the possible crosstalk between them is largely unknown. This study investigates the possible convergence between Wnt/β-catenin and EGFR signalling by gene and protein expression in eight rare pleural cancers, (6 epitelial MPM(eMPM), one sarcomatous MPM (sMPM) and one PSS tissues from patients treated at the Department of Thoracic Surgery, SS. Annunziata Hospital in Chieti, from 2013 to 2014. Fresh tumour tissues were evaluated for protein and gene expression by semi-quantitative Western blotting and qRT-PCR. Western blot for total β-catenin, reveals a low expression in sMPM compared to eMPMs. Moreover in one eMPM from a patient treated with neoadjuvant chemotherapy we observed a significant reduction of β-catenin. The PSS and eMPM-66 display higher amount of activate β-catenin vs total β-catenin. Using one of pleural normal tissue with the lower Ct value as a calibrator we observed a very strong expression in LEF1 trascripts in all tumors. APC increased in 3 eMPMs whereas the PSS and sMPM showed a lower APC expression compared to all samples. EGFR showed an overexpression in all tumors, particularly eMPM-22. The same sample indicate an ERB-b2 and ERB-b3 overexpression. Interestingly, ERB-b4 seems not expressed in all MPMs while it was over expressed in PSS. These preliminary data confirm the involvement of Wnt/β-catenin and EGFR pathways in pleural cancers. Future molecular treatment strategies for pleural malignancies could include Wnt and EGFR pathways antagonists.