Purpose: Glucose transporter type 1 (Glut1) plays a crucial role in cancer specific metabolism to adapt to the rapid growth and tumor microenvironment in diverse malignant tumors. We recently reported the relationship between Glut1 status and 18F-FDG uptake. PET-positive lesions had higher Glut1 expression than PET-negative lesions in both primary tumors and metastatic lymph nodes. In this study, it was showed that the clinical, pathological and prognostic features of Glut1 expression on primary lesions of esophageal squamous cell carcinoma.

Methods: Immunohistochemical staining of Glut1 and CD34 was performed using paraffin sections of tissues obtained from 145 resectable esophageal squamous cell carcinoma patients without preoperative treatment. Microvessel density was calculated from CD34 staining.

Results: Glut1 positivity was observed in 41 patients (28.2%) and associated with depth of invasion (odds ratio (OR)=2.984; 95% confidence interval (CI): 1.208-7.371; P=0.018) and vascular invasion (OR=2.771; 95% CI: 1.118-6.871; P=0.028) in multivariate analysis. Glut1 positivity was a significant disadvantage to both relapse-free survival (hazard ratio (HR)=2.021; 95% CI: 1.100-3.712; P=0.023) and esophageal cancer-specific survival (HR=2.223; 95% CI: 1.121-4.411; P=0.022) in univariate Cox hazard analysis, but was not independently associated with relapse-free survival or cancer-specific survival in multivariate analysis. The relationship between Glut1 expression and first relapse site was investigated. Glut1 positivity was not associated with lymph node recurrence (HR 1.009; 95% CI: 0.402-2.530; P=0.985) but was significantly associated with hematogenous recurrence (HR=3.701; 95% CI: 1.655-8.273; P=0.001) in univariate Cox hazard analysis. Microvessel density was calculated to evaluate angiogenesis and high microvessel density was associated with invasion depth (P=0.044) and vascular invasion (P=0.016). The median microvessel densities for Glut1-negative tumors and Glut1-positive tumors were 38.0 and 54.0, respectively. The microvessel density for Glut1-positive tumors was significantly higher than that of Glut1-negative tumors (Mann-Whitney U-test: P<0.001)

Conclusions: Glut1 expression was associated with hematogenous recurrence. The relationship between Glut1 expression and hematogenous recurrence may stem from an acquired survival ability resulting from upregulated Glut1 and angiogenesis to adapt to the tumor microenvironment. The findings provide evidence of the significance of Glut1 expression as a biomarker in esophageal squamous cell carcinoma.

Citation Format: Hiroshi Sawayama, Takatsugu Ishimoto, Masayuki Watanabe, Naoya Yoshida, Yoshifumi Baba, Hidetaka Sugihara, Daisuke Izumi, Hideo Baba. Glucose transporter 1 positivity on primary lesions of esophageal squamous cell carcinoma is associated with hematogenous recurrence. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3357. doi:10.1158/1538-7445.AM2014-3357