Expression of mutant p53 and of the multidrug resistant proteins P-glycoprotein and glutathione S-transferase-pi correlated in colorectal adenocarcinoma

Abstract

Objective. Accumulating studies suggest that multidrug resistance is related to expression of p53, P-glycoprotein (Pgp) and Glutathione S-Transferase-pi (GST-pi). This study was to estimate mutant p53 expression and its correlation with drug resistance related proteins Pgp and GST-pi expression in colorectal adenocarcinoma patients. Material and methods. Immunohistochemical ABC technique was used to detect the expression of mutant p53 protein, Pgp and GST-pi in 404 cases with colorectal adenocarcinoma. Results. A low frequency of mutant p53 accumulation was observed, consistent with findings in colorectal cancers (CRCs) from other Asian populations. Accumulation of mutant p53 was related to AJCC staging (p < 0.05). Pgp expression was significantly correlated with tumor location (p = 0.039) and gender (p = 0.043). The positive percentage of Pgp and GST-pi expression was all significantly higher in mutant p53 protein positive group than mutant p53 protein negative cases (r = 0.634, p < 0.001 and r = 0.680, p < 0.001, respectively). Conclusions. These findings demonstrate association of three biomarkers with clinicopathologic parameters of colorectal carcinoma, and overexpression of Pgp and GST-pi was closely correlated with mutant p53.

Key Words::

• Colorectal carcinoma
• glutathione S-transferase-pi
• immunohistochemistry
• mutant p53
• P-glycoprotein

Acknowledgements

We thank Rebekah Craig for providing English language and editorial assistance in the preparation of this manuscript. This study was supported by the National Natural Science Foundation of China (Grant No. 30671904, 30760014), the New Century Excellent Talent Supporting Project of Ministry of Education of China (Grant No. NCET-08-0923), the Cultivation Program for Reserve Talent of Middle-Young Aged Academic and Technology Leader of Yunnan Province (Grant NO. 2006Y01-12), the Key Program of Science and Technology Project of Kunming (Grant No. 07S060202), the Yunnan Provincial Applied Basic Research Program (Grant No. 2007C0022R, 2007C0025R, 2007C0023R), the Science and Technology Program of Yunnan Province (Grant No. 2007C009Z), the Yunnan Provincial Key Program for Applied Basic Research (Grant No. 2008CC006), the Innovation talent Team Program for Prevention and Treatment of High Incidence Lung Cancer of Yunnan Province (Grant No. 20080C014), and the international technology cooperation project of scientific and technological innovation program of Yunnan Province Science and Technology Agency (Grant No. 2009AC016).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.