Significance of GSTP1 for predicting the prognosis and chemotherapeutic efficacy in esophageal squamous cell carcinoma

Abstract

Abstract. Glutathione S-transferases (GSTs) have been reported to be activated in several types of cancers, including esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate whether GSTP1 protein expression is a useful predictor of the clinical outcome or drug resistance in ESCC. Immunohistochemistry was conducted with 75 ESCC resected specimens using a monoclonal antibody against GSTP1. The patients were divided into two groups according to the degree of GSTP1 staining, and the relationship between the GSTP1 level and the clinicopathological features was examined. Seventy-five patients were divided into low (grade 1, n=36) and high (grade 2, n=39) GSTP1 expression groups. The overall survival was significantly worse in the grade 2 patients than in the grade 1 patients (5-year survival rate, 78.5 vs. 51.2%; p=0.027). Cox proportional hazard analysis revealed that macroscopic type 3 or 4 disease (p=0.001), lymph node metastasis (p=0.010), and high GSTP1 expression (p=0.029) were independent predictors of a poor prognosis. With regard to the subgroup analysis among the 31 patients undergoing adjuvant chemotherapy, the grade 2 patients had a worse prognosis than did the grade 1 patients (5-year survival rate, 45.0 vs. 81.8%; p=0.081). This tendency was not observed in the subgroup without adjuvant chemotherapy (5-year survival rate, 51.7 vs. 59.9%; p=0.979). In conclusion, the GSTP1 expression is a good predictor of prognosis, and it may be closely related to the chemotherapeutic efficacy of 5-FU plus cisplatin in ESCC patients.

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“…In HaCaT cells, regulation of Nrf2 independent of GSTP1 expression may have evolved selectively with high proliferation capacity during immortalization (an ability to proliferate an unlimited number of times). As immortalization is a first step in carcinogenesis, a variety of human cancer cells, including breast, colon, kidney, lung, and ovary cancer cells, share genomic instability, loss of senescence genes, p53 mutation, and high expression of GSTP1 (Howells et al, ; Tidefelt et al, ; Yamamoto et al, ). Additionally, the role of GSTP1 in HaCaT cells may be distinct from normal cells (Schadich et al, ).…”

Glutathione S‐transferase Pi 1 is a valuable predictor for cancer drug resistance in esophageal squamous cell carcinoma

“…GSTP1 expression was mainly detected in the nuclei and cytoplasm of cancer cells, and also in the superficial layer of the normal esophageal epithelium (). The patients were divided into two groups, grade 1 and grade 2, on the basis of the judgement criteria of the previous study described in Materials and Methods . Twenty‐three patients (31.9%) of all 72 patients were divided into grade 1, and 49 patients (68.1%) were divided into grade 2 (Table ).…”

“…The sections were incubated with a second antibody using the avidin‐biotin‐peroxidase complex system (Vectastain Elite ABC Universal Kit) according to the manufacturer's instructions. Color development was carried out with diaminobenzidine tetrahydrochloride and hematoxylin . GSTP1 expression was divided into two groups: tissues of grade 1 were stained less than 90%, and tissues of grade 2 were stained over 90% of the cancer area as described in the previous study …”

“…Color development was carried out with diaminobenzidine tetrahydrochloride and hematoxylin . GSTP1 expression was divided into two groups: tissues of grade 1 were stained less than 90%, and tissues of grade 2 were stained over 90% of the cancer area as described in the previous study …”

“…In a previous study, we showed that high GSTP1 expression of the resected specimen was one of the independent predictors of a poor prognosis in ESCC patients who had undergone radical esophagectomy. Five‐year overall survival rate of patients with high GSTP1 expression was significantly lower than those with low GSTP1 expression in subgroup analysis among patients who underwent postoperative adjuvant chemotherapy . In the present study, we investigated the significance of GSTP1 expression in malignant potential and sensitivity to chemotherapy using ESCC cell lines, and immunohistochemistry of ESCC patients who underwent neoadjuvant chemotherapy was examined in resected tissues.…”