Expression of Glucose transporter-1 in Cervical Cancer and Its Precursors

Gynecol Oncol. 2002 Aug;86(2):138-43. doi: 10.1006/gyno.2002.6745.

Abstract

Objective: Increased glucose uptake and utilization is a known phenomenon exhibited by malignant cells. Overexpression of the glucose transporter protein family is thought to be the principal mechanism by which these cells achieve up-regulation. Our purpose is to determine glucose transporter-1 (GLUT 1) expression in squamous carcinoma of the cervix and precursor lesions.

Methods: Archival histologic sections were obtained from 31 cases of invasive squamous cell carcinoma (SCC) of the uterine cervix, 15 cases of high-grade cervical intraepithelial neoplasia, 5 cases of low-grade, and 9 normal cervices. Immunohistochemistry for GLUT 1 protein was performed using polyclonal GLUT 1 antibody (Dako, Carpinteria, CA) and the labeled streptavidin-biotin procedure.

Results: Compared to the internal control, the pattern of staining varied from weak (1+) to strong (3+) reactions. In normal cervix, 1+ GLUT 1 staining was seen in the basal cells of the squamous epithelium. All 31 (100%) cases of SCC were positive for GLUT 1. Positive reactions seemed more intense in tumor cells that were farther away from the stromal blood supply. There was a correlation between intensity of reaction for GLUT 1 and histologic grade of tumor (P = 0.0027) and with progression from normal or dysplastic lesions to invasive cancer (P = 0.0001). Intensity was a predictor of the presence of poorly differentiated tumor type. Low-grade CIN staining was seen in less than one-third of the epithelium, while in high-grade lesions the reaction was present in over one-half of the epithelium.

Conclusions: GLUT 1 is overexpressed in cervical carcinoma. The process appears to be related to grade of tumor but not to the progression from preneoplastic lesions. The results suggest that GLUT 1 overexpression is a late phenomenon in cellular transformation. Furthermore, the possible relation of expression to tumor blood supply suggests that the malignant cells may have an adaptive environmental ability to compensate for a compromised microenvironment.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cervical Intraepithelial Neoplasia / chemistry*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glucose Transporter Type 1
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Monosaccharide Transport Proteins / analysis*
  • Monosaccharide Transport Proteins / immunology
  • Neoplasm Invasiveness
  • Up-Regulation
  • Uterine Cervical Neoplasms / chemistry*

Substances

  • Glucose Transporter Type 1
  • Monosaccharide Transport Proteins
  • SLC2A1 protein, human