Abstract 2312: High ΔN/TA TP63 isoforms ratio is liked to the maintenance of an epithelial phenotype in Squamous cell lung cancer
Authors: Karine Pallier, Marine Desroches, Cristina Leschi, Leila El Khattabi, Aurelie Cazes, Claire Danel, Marc Riquet, Pierre Laurent-Puig, Helene Blons
Journal: Cancer Research (2010)

Abstract Squamous cell carcinoma of the lung (SCC) is a tumor that arises from bronchial epithelium. The transcription factor TP63, member of the TP53 family is crucial for epithelial development and different isoforms can be reactivated during carcinogenesis. Its role remains controversial and its relation with acquired invasive phenotype and epithelial to mesenchymal transition has not been fully explored in lung cancer. Here we report the phenotypic characterization of a series of 41 lung SCC, collected according to French Laws (CPP Ile de France II, 2008-A01074-51) and for which frozen tumor tissues were available for RNA extraction. Epithelial and mesenchymal markers: CDH1 (E-cadherin), JUP (Plakoglobin), VIM (Vimentin), CDH2 (N-cadherin) and TP63 isoforms (ΔNTP63 and TATP63) as well as TWIST1 and SNAIL reported to be linked to EMT and to interact with TP63 were analyzed at RNA level. Moreover, TP63 amplification was determined by quantitative PCR. We used real RTPCR to estimated the expression of each marker, a pool of non tumor lung tissue RNA (6 individuals) was used as reference as well as 3 reference genes (RPL13, YAP1, POLR2A) to calculate the ΔΔCt. CDH1, JUP, VIM, CDH2, ΔN and the TA TP63 isoforms were analyzed using SYBR Green technology; TWIST and SNAIL were analyzed using TaqMan probes with similar references. In this series, epithelial markers were associated together (p=0.001) as well as mesenchymal markers (p=0.0003). We confirmed that the TP63 locus at 3q28 was commonly amplified in lung SCC but this copy number change was not related to high ΔN/TA ratio (p=0.23). High ΔN/TA ratio was linked to high CDH1 expression (p=0.04), high JUP expression (p=0.01) or both (p=0.02) but not to high VIM or CDH2. At the opposite, TWIST1 expression was related to high VIM (p=0.02) and high CDH2 (p=0.008) or both (p=0.01). SNAIL was not expressed in this tumor series. TP53 mutations were not related to TP63 amplification nor to high ΔN/TA ratio and both event seem to be independent in this series. To conclude, the expression of epithelial and mesenchymal markers did not match to the high, moderate or low differentiation status determined by the pathologist and allowed the clustering of different tumor groups. In this tumor series, high ΔN/TA ratio was linked to the maintenance of epithelial characteristics whereas low ΔN/TA ratio and TWIST expression was related to EMT. Clinical data analysis is ongoing to study the impact of these associations on patient outcome. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2312.