Both GLUT-1 and GLUT-14 are Independent Prognostic Factors in Gastric Adenocarcinoma

Ann Surg Oncol. 2015 Dec:22 Suppl 3:S822-31. doi: 10.1245/s10434-015-4730-x. Epub 2015 Jul 17.

Abstract

Background: The role of glucose transporter 14 (GLUT-14/SLC2A14) in tumor biology is entirely unknown, and the significance of hypoxia inducible factor 1-alpha (HIF1-α) for gastric adenocarcinoma is controversial. The impact of GLUT-1/SLC2A1 has never been confirmed in a Caucasian cohort.

Methods: Between 1996 and 2007, 124 patients underwent gastrectomy for gastric adenocarcinoma. Tumor sections were incubated with GLUT-1, GLUT-14, and HIF1-α antibodies. Expression was analyzed for correlations with histopathology, marker coexpression, and patient survival by uni- and multivariate analyses.

Results: Expressions of GLUT-1, GLUT-14, and HIF1-α were detectable in 50, 77.4, and 27.1 %, respectively. Expression of GLUT-1 was associated with pT-category (p = 0.019), pN-category (p = 0.019), tubular (WHO, p = 0.008), and intestinal (Lauren classification; p = 0.002) histologic subtypes. Expression of GLUT-14 was correlated with pT category (p = 0.043), whereas HIF1-α did not show any correlation with histopathology or survival. The median survival period was 14 months (95 % confidence interval [CI] 9.2-18.8 months) for GLUT-1-positive patients and 55 months (95 % CI 25.8-84.2; p = 0.01) for GLUT-1-negative patients. An inferior prognosis also was seen for GLUT-14-positive cases compared with GLUT-14-negative cases (p = 0.004). Thus, worst survival was seen with both GLUT-1- and GLUT-14-positive expression followed by single-positive and then double-negative cases (p = 0.004). In multivariate analysis including International Union Against Cancer (UICC) stages, R category, Lauren classification, surgery alone versus neoadjuvant/perioperative chemotherapy, and marker expression as covariates, GLUT-1 (p = 0.011) and GLUT-14 (p = 0.025) kept their prognostic independence.

Conclusions: The study findings suggest that detection of GLUT-1 and GLUT-14 is of high prognostic value. It gives additional information to UICC stages and identifies patients with inferior prognosis. If confirmed in prospective studies, these markers need to be considered for future classification systems.

MeSH terms

  • Adenocarcinoma / classification
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Gastrectomy
  • Glucose Transport Proteins, Facilitative / metabolism*
  • Glucose Transporter Type 1 / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Stomach Neoplasms / classification
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / surgery
  • Survival Rate
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Glucose Transport Proteins, Facilitative
  • Glucose Transporter Type 1
  • SLC2A14 protein, human