Decreased expression of GST pi is correlated with a poor prognosis in human esophageal squamous carcinoma

BACKGROUND: Glutathione S-transferase pi (GST pi) is a subgroup of GST family, which provides cellular protection against free radical and carcinogenic compounds due to its detoxifying function. Expression patterns of GST pi have been studied in several carcinomas and its down-regulation was implicated to be involved in malignant transformation in patients with Barrett's esophagus. However, neither the exact role of GST pi in the pathogenesis nor its prognostic impact in squamous esophageal carcinoma is fully characterized. METHODS: Immunohistochemistry was used to investigate GST pi expression on 153 archival squamous esophageal carcinoma specimens with a GST pi monoclonal antibody. Statistic analyses were performed to explore its association with clinicopathological factors and clinical outcome. RESULTS: The GST pi expression was greatly reduced in tissues of esophageal carcinomas compared to adjacent normal tissues and residual benign tissues. Absent of GST pi protein expression in cytoplasm, nuclear and cytoplasm/nucleus was found in 51%, 64.7% and 48% of all the carcinoma cases, respectively. GST pi deficiency in cytoplasm, nucleus and cytoplasm/nucleus was significantly correlated to poor differentiation (p < 0.001, p < 0.001 and p < 0.001, respectively). UICC stage and T stage were found significantly correlated to negative expression of GST pi in cytoplasm (p < 0.001 and p = 0.004, respectively) and cytoplasm/nucleus (p = 0.017 and p = 0.031, respectively). In univariate analysis, absent of GST pi protein expression in cytoplasm, nucleus and cytoplasm/nucleus was significantly associated with a shorter overall survival (p < 0.001, p < 0.001 and p < 0.001, respectively), whereas only GST pi cytoplasmic staining retained an independent prognostic significance (p < 0.001) in multivariate analysis. CONCLUSIONS: Our results show that GST pi expression is down regulated in the squamous esophageal carcinoma, and that the lack of GST pi expression is associated with poor prognosis. Therefore, deficiency of GST pi protein expression may be an important mechanism involved in the carcinogenesis and progression of the squamous esophageal carcinoma, and the underlying mechanisms leading to decreased GST pi expression deserve further investigation.