Wnt/!-catenin and EGFR pathways evaluation in primary pleural cancers

OBJECTIVE: 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 unified by a poor prognosis. Wnt/"-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. MATERIALS AND METHODS: This study investigates the possible convergence between Wnt/"-catenin and EGFR signaling by gene and protein expression in eight pleural cancers, six 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 Western blotting and qRT-PCR analysis. RESULTS: Western blotting for total "- catenin reveals a lower expression in sMPM compared to eMPMs and a strong EGFR activation. The PSS and 1/5 eMPM display higher amount of activated "- catenin compared to the remaing samples. Gene expression of Wnt/"-catenin signalling components highlights a very strong expression of LEF1 transcription factor in all cancers. APC gene increases about three times in 3/5 eMPMs whereas the PSS, sMPM and 1/5 eMPM showed a lower expression compared to pleural non-cancerous tissues. WNT3a a prototype of the canonical signaling showed an opposite trend respect to APC. WNT5a, a prototype of the noncanonical pathway, decreased although the "-catenin was expressed al low levels. Axin2, LRP6 and BCL9 decreased. ErbB reseptors were shown to be overexpressed in all tumors analyzed, except ErbB4 overexpressed only in PSS. Moreover, in one eMPM from a patient treated with neoadjuvant chemotherapy we observed a reduction of Wnt/"-catenin and EGFR signalling markers, although the reduction was less marked in LEF1 and ErbB3 genes. CONCLUSION: These preliminary data confirm the involvement of Wnt/"-catenin and ErbB pathways in pleural cancers and also underlined the noncanonical Wnt signalling implication. To highlight the solutions of unanswered questions, will be imperative the rational exploration of these pathways in future molecular treatment strategies.