Expression of Glucose Transporter-1, Hexokinase-II, Proliferating Cell Nuclear Antigen and Survival of Patients with Pancreatic Cancer

Abstract

Objectives: 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) has been shown to be useful in diagnosis and staging of pancreatic cancer. However, the prognostic value of FDG-PET remains controversial. The aim of this study was to evaluate relations between the factors suggested to be related to the FDG accumulation in tumor tissue, such as glucose transporter-1 (GLUT-1), hexokinase type-II (HK-II), proliferating cell nuclear antigen (PCNA), and survival of pancreatic cancer patients. Methods: Histological specimen of pancreatic cancer obtained from seventy-four consecutive patients were evaluated for the expression of GLUT-1, HK-II, and PCNA by visual analysis of immunohistochemical staining of paraffin sections from the tumor specimens using anti-GLUT-1, anti-HK-II, and anti-PCNA antibody, respectively. The percentages of cells strongly expressing GLUT-1, HK-II and PCNA were scored on a 5-point scale (1 = 0–20 percent, 2 = 20–40 percent, 3 = 40–60 percent, 4 = 60–80 percent, 5 = 80–100 percent). After initial treatment, each patient was followed-up and survival time was recorded. Median survival curves of the patients with different levels of GLUT-1, HK-II, and PCNA expression were evaluated using the Kaplan-Meier method. Statistical significance of the differences in survival was calculated with the log rank test. Results: Median survival of examined patients showed no relation with the levels of GLUT-1 expression, while patients with low expression of HK-II (HK-II index < 3) had significantly shorter survival than those with higher expression of HK-II (HK-II index ≥ 3) (6.5 ± 4.1 versus 12.9 ± 22.4 months, respectively, p < 0.05). Median survival of examined patients also showed significant relations with the levels of PCNA expression. Patients with low expression of PCNA (PCNA index < 4) had significantly longer survival than those with higher expression of PCNA (PCNA index ≥ 4) (11.9 ± 20.1 versus, 5.8 ± 10.8 months, respectively, p < 0.01): Conclusions: Our results showed that the expression of GLUT-1 had no prognostic value in the examined patients with pancreatic cancer. On the other hand, high levels of HK-II expression and low levels of PCNA expression may allow accurate identification of the patient with longer survival who may benefit from intensive anticancer treatment.

Keywords:

• Glucose transporter-1
• Hexokinase-II
• Proliferating cell nuclear antigen
• Pancreatic cancer
• Survival