Expression of p53 family members and CD44 in oral squamous cell carcinoma (OSCC) in relation to tumorigenesis

Abstract

Oral squamous cell carcinomas (OSCCs) aredescribed as the result of a multistep tumorigenesisprocess. In order to develop useful diagnosis of pre-malignant lesions, expression of p53 family membersand the cancer stem cell (CSCs) marker, CD44v6, werestudied in histologically normal oral epithelium,precancerous lesions and succeeding invasive OSCCs.p53 was expressed focally in normal epithelium adjacentto tumors, while expression was high in intra-epithelialneoplasia and moderate in OSCC. p63 nuclear stainingwas important in basal and suprabasal layers ofhistologically normal oral mucosa and in immaturecompartments of premalignant lesions and cancer. Inepithelium without neoplasia, intense p73 staining wasobserved in the basal layer, while focal expression waspresent in suprabasal layers. Most immature dysplasticareas showed either high or moderate staining, whereasthose in OSCCs expressed low and moderate p73 levelexpression. CD44v6 was only expressed in poorlydifferentiated areas of epithelium, altered or not. p53,p63 and p73 positive stainings were statistically relatedin intra-epithelial neoplasia to tumours. Analysis ofTP53 mutations in 17% of tumours principally revealedG>A and A>G transitions. No relation was observedbetween this mutational profile and differentimmunostainings. In conclusion, our results support thatimmunostaining of p53 family members might behelpful in diagnosis and monitoring of high-risk pre-malignant lesions of oral epithelium. The combination ofstaining patterns of p63, p73αand CD44v6 enabled us to isolate phenotypic undifferentiated or transientamplifying areas, reflecting the immaturity of the tumourcell lineage. While CD44v6 expression is an interestingmarker of such epithelial cells, it is not specific enoughto be useful alone and other phenotypic markers areneeded.