Particular gene upregulation and p53 heterogeneous expression in TP53-mutated maxillary carcinoma.

Abstract

It has been demonstrated that tumor protein p53 (TP53) mutation in maxillary squamous cell carcinoma, is more treatment-resistant compared with the carcinoma without TP53 mutation. However, the association between TP53 mutation and treatment resistance remains unclear. As a first step in understanding the biological differences between tumors with and without TP53 mutation, a comprehensive gene expression analysis of maxillary squamous cell carcinoma with or without TP53 mutation was performed. A total of 42 genes were identified to be differentially expressed by >4-fold. Quantification of their mRNA using quantitative polymerase chain reaction indicated 18 genes with high expression and three genes with low expression in TP53 mutated tumors vs. TP53 wild-type tumors. The 18 genes included eight cell adhesion (DSC3, GRHL1, EPPK1, PROM2, ANXA8, DSP, JUP, and KRT6B) and four cell growth inhibition (SFN, CLCA2, SAMD9 and TP63) genes. Among these genes, DSC3, SFN, and CSTA, whose expression was markedly increased, also demonstrated high protein expression in immunohistochemical staining of TP53 mutated tumors. The TP53 mutated tumors demonstrated high nuclear staining of the TP53 protein only in tumor cells at the tumor margins adjacent to the stroma, whereas the tumor interior was negative for TP53. However, all tumor cells of TP53 wild-type tumors exhibited positive nuclear staining for the TP53 protein. The combined findings suggest that TP53 mutated tumors possess a phenotype opposite to that associated with cancer progression and malignant transformation, and exhibit tumor cell heterogeneity between the tumor interior and margins.