Interleukin-2 gene expression is a new biological prognostic marker in hepatocellular carcinomas.
BACKGROUND
Cytokines produced by tumor cells and tumor-infiltrating lymphocytes (TIL) appear to regulate tumor cell growth. The present study analyzed the correlation between local immune responses and cytokine gene expression levels in patients with primary hepatocellular carcinoma (HCC).


METHODS
The gene expression levels of interleukin-2 (IL-2) and -12 (IL-12) were evaluated quantitatively by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and compared with the density of CD8+ TIL detected by immunohistochemistry in 59 surgically resected HCCs.


RESULTS
IL-2 gene expression was detected in 33 (56%) and IL-12 gene expression in 39 (66%) of 59 HCCs. Tissue infiltrating CD8+ T lymphocytes in tumors were significantly suppressed compared with noncancerous liver tissues. The CD8+ T cell density of tumors with IL-2 gene expression was higher than that of tumors without IL-2 gene expression (p = 0.002). However, such a correlation was not detected in tumors with or without expression of IL-12 genes. Patients with IL-2 positive tumors had a favorable prognosis. IL-2 gene expression was detected as an important prognostic factor independent of tumor stage.


CONCLUSIONS
These findings indicate that in HCCs, tumor-infiltrating CD8+ T cells might be activated by IL-2 produced by TIL and IL-2 gene expression in tumors may be an important prognostic biomarker in HCC.
Ikeguchi
Masahide
M
Division of Surgical Oncology, Faculty of Medicine, Tottori University, Yonago, Japan. masaike@grape.med.tottori-u.ac.jp
Hirooka
Yasuaki
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000150:complications / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000473:pathology; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D007376:Interleukin-2; D018664:Interleukin-12