Glutathione S-transferase Pi expression predicts response to adjuvant chemotherapy for stage C colon cancer: a matched historical control study

Betty P C Lin,Owen F Dent,Stephen J Clarke,Mark Molloy,Pierre H Chapuis,Les Bokey,Caroline L-S Fung,Maija Kohonen-Corish,Charles Chan,Graham Robertson,Candice Clarke,Lucy Jankova,King L Tan

doi:10.1186/1471-2407-12-196

Abstract

BackgroundThis study examined the association between overall survival and Glutathione S-transferase Pi (GST Pi) expression and genetic polymorphism in stage C colon cancer patients after resection alone versus resection plus 5-fluourouracil-based adjuvant chemotherapy.MethodsPatients were drawn from a hospital registry of colorectal cancer resections. Those receiving chemotherapy after it was introduced in 1992 were compared with an age and sex matched control group from the preceding period. GST Pi expression was assessed by immunohistochemistry. Overall survival was analysed by the Kaplan-Meier method and Cox regression.ResultsFrom an initial 104 patients treated with chemotherapy and 104 matched controls, 26 were excluded because of non-informative immunohistochemistry, leaving 95 in the treated group and 87 controls. Survival did not differ significantly among patients with low GST Pi who did or did not receive chemotherapy and those with high GST Pi who received chemotherapy (lowest pair-wise p = 0.11) whereas patients with high GST Pi who did not receive chemotherapy experienced markedly poorer survival than any of the other three groups (all pair-wise p <0.01). This result was unaffected by GST Pi genotype.ConclusionStage C colon cancer patients with low GST Pi did not benefit from 5-fluourouracil-based adjuvant chemotherapy whereas those with high GST Pi did.

Highlights

This study examined the association between overall survival and Glutathione S-transferase Pi (GST Pi) expression and genetic polymorphism in stage C colon cancer patients after resection alone versus resection plus 5-fluourouracil-based adjuvant chemotherapy
Between May 1 1992, when adjuvant chemotherapy was introduced in this hospital, and December 31 2004 resections for stage C colon cancer were performed on 263 patients, of whom 104 (40%) received adjuvant chemotherapy
The presence of high GST Pi in colon tumours may confer a selective advantage on malignant colon cells, as increased production of reactive oxygen species is a feature of cancer progression [15]

Summary

Introduction

This study examined the association between overall survival and Glutathione S-transferase Pi (GST Pi) expression and genetic polymorphism in stage C colon cancer patients after resection alone versus resection plus 5-fluourouracil-based adjuvant chemotherapy. Glutathione S-transferase Pi (GST Pi) is found in the cell nucleus, cytoplasm and mitochondria of a wide range of normal and neoplastic tissues and is expressed in colorectal cancer [1,2]. We have shown a high level of expression of GST Pi to be associated with adverse histological features and diminished overall survival after adjustment for other prognostic factors in a large series of patients who had a potentially curative resection for stage C colonic adenocarcinoma [5]. The prognostic or predictive value of GST Pi expression or genomic polymorphisms for outcomes after chemotherapy has been examined in several studies. There is some evidence for GST Pi as a prognostic biomarker but little evidence for its predictive ability

Objectives

Methods

Results

Discussion

Conclusion