DeltaN TP63 reactivation, epithelial phenotype maintenance, and survival in lung squamous cell carcinoma

Genes, active during normal development, are frequently reactivated during neoplastic transformation and may be related to progression. One of them, the transcription factor TP63, is crucial for pulmonary epithelial development and a possible target of the recurrent 3q amplifications in lung squamous cell carcinoma (SCC). Here, we explored whether TP63 reactivation could be associated to cancer progression in lung SCC through an epithelial to mesenchymal transition. We studied TP63 amplification and TP63 expression at RNA and protein levels and we analyzed the ΔNTP63/TATP63 ratio that quantifies the proportion of the isoform lacking the transactivation domain/the isoform containing the transactivation domain. We correlated TP63 status to survival and to the expression of epithelial (E-cadherin and plakoglobin) and mesenchymal (N-cadherin, vimentin, TWIST1, and SNAIL) markers. We found that high ΔN/TA TP63 ratio was related to high E-cadherin and plakoglobin mRNA levels (P < 0.05) and that E-cadherin mRNA level was the only marker related to survival. Kaplan–Meier survival curves stratified according to the expression level of E-cadherin showed, as already reported in breast cancer, that patients with low (first quartile) or high (last quartile) E-cadherin expression had a worse survival with respect to patients with intermediate E-cadherin expression. Altogether, our results indicate that a reactivation of ΔNTP63 is linked to the maintenance of epithelial markers and suggest that E-cadherin has a dual role in lung SCC.

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