Relationship of P-glycoprotein and p53 protein to chemosensitivity in colorectal cancer

Background: Resistance of tumors to chemotherapeutic agents is a major problem in cancer treatment. Recent advances in molecular biology have shown a role for oncogenes in this resistance. Methods: We determined the positive or negative expression of P-glycoprotein and mutant p53 protein by immunohistochemistry on 101 human colorectal cancer and correlated the expression of these proteins with the chemosensitivity of the tumors to various anticancer agents using the succinate dehydrogenase inhibition (SDI) test. Results: Fifty-five (54.5%) of 101 tumors expressed P-glycoprotein and 53 (52.5%) expressed a mutant p53 protein. Thirty-seven of 55 tumors positive for P-glycoprotein also expressed a mutant p53 protein. The association between the coexpression of P-glycoprotein and p53 protein was statistically significant (P= 0.001 ). Neither the expression of P-glycoprotein nor p53 protein affected the chemosensitivity of the tumor to doxorubicin hydrochloride, aclarubicin hydrochloride, pirarubicin, epirubicin hydrochloride, mitomycin C, 5-fluorouracil, cisplatin, carboplatin, or etoposide. However, a positive correlation was found between the control optical density and chemosensitivity in the P-glycoprotein or mutant p53 protein negative tumors. Oppositely, some P-glycoprotein or mutant p53 protein positive tumors showed low chemosensitivity in spite of their high control optical density. Conclusions: A highly statistically significant coexpression of P-glycoprotein and mutant p53 protein was found in colorectal cancer. Furthermore, differences in cell growth between the tumor samples indicate the possibility that the expression of P-glycoprotein and mutant p53 protein in colorectal cancer tumors could be associated with chemoresistance. © JSCO/CLJ 1997.