title: P-glycoprotein is positively correlated with p53 in human oral pre-malignant and malignant lesions and is associated with poor prognosis.
abstract: 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 immunohistochemical and flow-cytometric analyses. The relationship between Pgp and p53 protein accumulation and clinicopathological 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.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi. rralhan@medinst.ernet.in
authors.forename: R
authors.initials: R
authors.lastname: Ralhan
authors.forename: R K
authors.initials: RK
authors.lastname: Swain
authors.forename: S
authors.initials: S
authors.lastname: Agarwal
authors.forename: J
authors.initials: J
authors.lastname: Kaur
authors.forename: N
authors.initials: N
authors.lastname: Nath
authors.forename: G
authors.initials: G
authors.lastname: Sarkar
authors.forename: M
authors.initials: M
authors.lastname: Mathur
authors.forename: N K
authors.initials: NK
authors.lastname: Shukla
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007194:India; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism; D011379:Prognosis; D012907:Smoking; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000096:biosynthesis