Clinicopathologic significance of GLUT1 expression and its correlation with Apaf-1 in colorectal adenocarcinomas

Abstract

Aim: To investigate the role of glucose transporter 1 (GLUT1) expression in colorectal carcinogenesis and evaluate the correlation with clinicopathological parameters and apoptosis-activating factor-1 (Apaf-1) expression in colorectal adenocarcinomas.

Methods: We used tissue microarrays consisting of 26 normal mucosa, 50 adenomas, 515 adenocarcinomas, and 127 metastatic lesions. Medical records were reviewed and clinicopathological analysis was performed.

Results: GLUT1 expression was absent in normal mucosa and low or moderately apparent in 19 cases (38.0%) of 50 adenomas. However, GLUT1 expression was detected in 423 (82.1%) of 515 adenocarcinomas and in 96 (75.6%) of 127 metastatic lesions. GLUT1 expression was significantly correlated with female gender (P = 0.009), non-mucinous tumor type (P = 0.045), poorer differentiation (P = 0.001), lymph node metastasis (P < 0.001), higher AJCC and Dukes stage (P < 0.001 and P < 0.001, respectively). There was a significant inverse correlation between GLUT1 expression and Apaf-1 expression (P = 0.001). In univariate survival analysis, patients with GLUT1 expression demonstrated poor overall survival and disease-free survival (P = 0.047 and P = 0.021, respectively, log-rank test).

Conclusion: GLUT1 expression was frequently increased in adenocarcinomas and metastatic lesions. GLUT1 expression was significantly correlated with poorer clinicopathologic phenotypes and survival of patients with colorectal adenocarcinomas.

Keywords: Adenocarcinoma; Apoptosis-activating factor-1; Colorectum; Glucose transporter 1; Prognosis; Survival.

Figure 1

Representative photomicrograph of glucose transporter 1 immunostaining in normal mucosa (A), tubular adenoma with low grade dysplasia (B), tubular adenoma with high grade dysplasia (C), and adenocarcinoma (D). The glucose transporter 1 was stained in the cytoplasmic membrane of the cells.

Figure 2

Representation showing the difference of mean grading score of glucose transporter 1 expression in normal mucosa, tubular adenomas with low grade dysplasia, tubular adenomas with high grade dysplasia, adenocarcinomas, and metastatic lesions (lymph nodes and distant organs). One-way ANOVA test was used. GLUT1: Glucose transporter 1; LGD: Low grade dysplasia; HGD: High grade dysplasia.

Figure 3

Cumulative overall survival curves (A) and disease-free survival curves (B) according to glucose transporter 1 expression in 515 colorectal cancer patients (Kaplan-Meier method with log-rank test). GLUT1: Glucose transporter 1.