Expression of thymidylate synthase and glutathione-s-transferase π in patients with esophageal squamous cell carcinoma

Abstract

AIM:To investigate the expression of thymidylate synthase (TS) and glutathione-s-transferase π (GST-π) in esophageal squamous cell carcinoma and their association with the clinicopathologic characteristics. METHODS:Immunohistochemical methods were used to detect the expression of TS and GST-π in surgically resected formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma (ESCC) tissue sections from 102 patients (median age, 58 years) and in 28 normal esophageal mucosa (NEM) samples. The relationship between TS and GST-π expression and clinicopathologic factors was examined. RESULTS:The expression of TS and GST-π was not statistically significantly associated with age of the patients, tumor size, lymph node metastasis, depth of invasion or tumor stage. TS staining was positive in 17.86% of normal esophageal mucosa and in 42.16% of ESCC samples (P < 0.05). The expression level of TS was not only significantly lower in well-differentiated (21.88%) than in poorly-differentiated carcinomas (51.43%, P < 0.05), but was also significantly higher in samples from male patients (46.51%) than from female patients (18.75%, P < 0.05). GST-π was positively stained in 78.57% of normal esophageal mucosa and in 53.92% of ESCC samples (P < 0.05). The expression level of GST-π was also significantly higher in welldifferentiated carcinomas (65.63%) than in poorlydifferentiated carcinomas (35.00%, P < 0.05).

Nrf2-dependent and Nrf2-independent induction of phase 2 detoxifying and antioxidant enzymes during keratinocyte differentiation

“…In contrast, low HO-1 expression is associated with lymph node metastasis in tongue SCC [26]. In esophageal SCC, the levels of GST expression in well-diVerentiated SCC are higher than those in poorly diVerentiated SCC [8]. The present study shows that a group of phase 2 enzymes are up-regulated in relation to the degree of cell diVerentiation in normal KC or SCC.…”

A Pilot Study to Investigate the Role of Thymidylate Synthase as a Marker of Prognosis for Neoadjuvant Chemotherapy in Gastric and Gastro-Oesophageal Junction Adenocarcinoma

“…At the cellular level TS expression was observed both in the nucleus and the cytoplasm. In the literature, variations are observed in scoring for TS: nuclear [20], cytoplasmic, [19] and both nuclear/cytoplasmic [11]. In our study only the nuclear staining was considered.…”

“…In oesophageal cancer, increased TS expression has been recognised to be associated with poor differentiation [11], nonresponse to chemotherapy [12], and tumour recurrence [13]. In gastric cancer TS expression has been studied as a predictive marker of response to chemotherapy [14–16] and poor differentiation [17].…”

Inhibition of glutathione metabolism attenuates esophageal cancer progression

“…For example, GSTO1, GSTP1 and GST-pi have been recognized as tumor-associated antigens and act as indicators of prognosis in human ESCC. 5 , 6 , 7 Moreover, previous findings have demonstrated that a GSTM1 deletion polymorphism is associated with an increased ESCC risk. 8 In contrast, another study has demonstrated that the GSTM1 non-null genotypes are highly represented in ESCC patients compared with control patients in China.…”