Immunohistochemical Expression of p53 Protein and P-glycoprotein and its Prognostic Significance in Osteosarcoma

Lee, Sang Hoon; Park, Yong Bum; Kim, Han Soo; Kim, Chong Jai; Kim, Woo Jin; Lee, Han Koo

Abstract

PURPOSE: The principal cause of treatment failure in osteosarcoma is drug resistance. Multidrug resistance (MDR), mediated by P-glycoprotein (P-gp), is an in vitro phenomenon, resulting in becoming cross-resistant to structurally unrelated drugs. P-gp expression was related to drug resistance, prognosis and recurrence in osteosarcoma. p53 gene regulates genomic stability. Mutant p53 protein causes loss of tumor suppression. Co-expression of mutant p53 protein and P-gp was related to short survival, malignancy and drug resistance in malignant tumors. Wild type p53 protein in SaOS-2 cell line down-regulates the transcription of mdr1 gene. The purpose of this study was to evaluate the expression of mutant p53 protein and P-gp in osteosarcoma and its prognostic significance.
MATERIALS AND METHODS
Fifty-two archival pathologic tissues were examined with immunohisto-chemistry. Positive expression was defined if more than 10% of tumor cells were stained.
RESULTS
Expression rate of mutant p53 protein was 63% and rate of P-gp was 35%. Correlation between mutant p53 protein and P-gp expression was significant (P=0.0008). Co-expression of mutant p53 protein and P-gp was the strongest prognostic factor for shorter survival by multivariate analysis (P=0.0004).
CONCLUSIONS
Nuclear accumulation of mutant p53 protein was significantly related to P-gp expression in osteosarcoma, Co-expression of mutant p53 protein and P-gp is an independent unfavorable prognostic factor in osteosarcoma