High expression of glucose transporter 1 on primary lesions of esophageal squamous cell carcinoma is associated with hematogenous recurrence.
OBJECTIVE
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. This study examined 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-embedded 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 it was observed that Glut1 positivity was significantly associated with high microvessel density (P < 0.001).


CONCLUSIONS
Glut1 expression was associated with hematogenous recurrence. The findings provide evidence of the significance of Glut1 expression as a biomarker.
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Hiroshi
H
Sawayama
Takatsugu
T
Ishimoto
Masayuki
M
Watanabe
Naoya
N
Yoshida
Yoshifumi
Y
Baba
Hidetaka
H
Sugihara
Daisuke
D
Izumi
Junji
J
Kurashige
Hideo
H
Baba
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D055806:Microvessels / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human