Expression of glucose transporter-1, hexokinase-II, proliferating cell nuclear antigen and survival of patients with pancreatic cancer.
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.
Lyshchik
Andrej
A
Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. andrej.lyschik@vanderbilt.edu
Higashi
Tatsuya
T
Hara
Tadashi
T
Nakamoto
Yuji
Y
Fujimoto
Koji
K
Doi
Ryuichiro
R
Imamura
Masayuki
M
Saga
Tsuneo
T
Togashi
Kaori
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D051272:Glucose Transporter Type 1 / Q000032:analysis*; D006593:Hexokinase / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000201:enzymology / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D013997:Time Factors
D051272:Glucose Transporter Type 1; D018809:Proliferating Cell Nuclear Antigen; D006593:Hexokinase