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Cancer Investigation

Expression of glucose transporter-1, hexokinase-II, proliferating cell nuclear antigen and survival of patients with pancreatic cancer.

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Andrej Lyshchik
Tatsuya Higashi
Tadashi Hara
Yuji Nakamoto
Koji Fujimoto
Ryuichiro Doi
Masayuki Imamura
Tsuneo Saga
Kaori Togashi

Keywords

Abstract

OBJECTIVE

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.

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