P‐glycoprotein is positively correlated with p53 in human oral pre‐malignant and malignant lesions and is associated with poor prognosis

P‐glycoprotein (Pgp) encoded by the MDR1 gene, a predictor of chemoresistance, may also serve as a prognosticator of clinical outcome in cancer patients. The mutant tumour‐suppressor p53 protein has been shown to activate the MDR1 promoter, whereas the wild‐type p53 represses this activity in cultured cells. We have described the differential expression of Pgp and p53 proteins in betel‐ and tobacco‐related oral tumorigenesis in the Indian population. Herein, Pgp expression was analysed in relation to p53 protein accumulation in pre‐malignant and malignant oral lesions by immuno‐histochemical and flow‐cytometric analyses. The relationship between Pgp and p53 protein accumulation and clinico‐pathological parameters as well as prognosis was determined. Expression of Pgp was observed in 81% of oral squamous cell carcinomas (SCCs) and 71% of pre‐malignant lesions. Sixty‐five of 75 p53‐positive oral SCCs and 21/24 p53‐positive pre‐malignant lesions showed expression of Pgp. Significant correlation between Pgp and p53 expression was found not only in oral SCCs but also in pre‐malignant lesions. Co‐expression of Pgp and p53 proteins was indicative of poor prognosis. Follow‐up studies of 35 patients showed that 7 of 10 oral SCCs with accumulation of Pgp and p53 proteins also exhibited shorter disease‐free survival (recurrence/metastases). Our findings provide clinical evidence for a significant association between Pgp and p53 protein expression in oral tumorigenesis and may account for the aggressive nature of the tumour and poor prognosis. Int. J. Cancer (Pred. Oncol.) 84:80–85, 1999. © 1999 Wiley‐Liss, Inc.