The stem cell markers expression CD44v6 and podoplanin in lip cancer: clinical significance

Abstract

This study aimed to analyze the immunoexpression of cancer stem cell markers, CD44v6, and podoplanin in 91 patients with lip squamous cell carcinomas (LSCC). The immunostaining of podoplanin and CD44v6 was evaluated in ten high-power fields (× 400 magnification) at the invasive front of LSCC, using a semi-quantitative score method. Chi-square test or Fisher's exact test was used to verify the association of podoplanin and CD44v6 expressions with clinicopathologic variables. Spearman's correlation test was used to analyze the correlation between the two antibodies in lip cancer. Disease-free survival probabilities in 5 and 10 years were estimated according to the Kaplan-Meier method and compared using the log-rank test. The independent effects of the significant variables were analyzed by Cox proportional hazards regression model. A strong podoplanin expression was observed in the membrane and cytoplasm of most lip tumor cells, and this was inversely associated with locoregional recurrence (p = 0.028) and with histopathological grade of malignancy (p = 0.026). Additionally, CD44v6 immunostaining was strongly expressed in the membrane of tumor cells in 95.4% of the LSCC. Patients with strong membranous (p = 0.016) or strong cytoplasmic (p = 0.030) podoplanin-positive tumors resulted in significantly better disease-free survival than those who had podoplanin weak/negative tumors, confirming podoplanin expression as a favorable independent prognostic factor. Podoplanin and CD44v6 were strongly expressed by tumor cells and podoplanin immunoexpression can help to determine lip cancer patients with lower risk for disease recurrence.

Keywords: Lip; Podoplanin; Squamous cell carcinoma; cd44 antigens.