PMID- 15870936 OWN - NLM STAT- MEDLINE DCOM- 20050919 LR - 20201212 IS - 1021-335X (Print) IS - 1021-335X (Linking) VI - 13 IP - 6 DP - 2005 Jun TI - Relative expression levels of Th1 and Th2 cytokine mRNA are independent prognostic factors in patients with ovarian cancer. PG - 1153-8 AB - The aim of the present study was to examine mRNA expression levels of Th1 (TNF-alpha , IFN-gamma, and IL-12p40) and Th2 (IL-6 and IL-10) cytokines for any association with clinicopathological characteristics of epithelial ovarian cancer. mRNA was isolated, and cDNA prepared from 40 samples of epithelial ovarian cancers. Expression level of each cytokine mRNA was examined by the real-time PCR technique (GAPDH gene, internal control). Expression ratio (target gene/GAPDH) was used to evaluate gene expression. Results were analyzed against clinical stage, histological grade, and histological type. Prognostic significance of expression levels of each combination of Th1/Th2 values was assessed. Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) expression levels were significantly higher in serous adenocarcinoma than in non-serous adenocarcinoma (p<0.05), but with no difference between individual cytokine mRNA expression levels and clinical stage or histological grade. Log-rank testing showed that high TNF-alpha mRNA expression (p=0.033) and the diameter of largest residual lesion at initial surgery (p=0.012) significantly correlate with longer survival in advanced stage (II/III/IV) ovarian carcinomas. In examining all combinations of Th1/Th2 expression values, the most significant association was between high IFN-gamma.IL-12p40/IL-6 expression levels and better prognosis in advanced stage (II/III/IV) ovarian carcinomas (p=0.004). In multivariate analysis, high IFN-gamma.IL-12p40/IL-6 expression (p=0.009) and the diameter of residual lesion (p=0.011) remained significantly associated with survival, whereas high TNF-alpha expression lost significance. In conclusion, Th1 and Th2 cytokines might play an important role in regulating the immune reaction in epithelial ovarian cancer cells. IFN-gamma.IL-12p40/IL-6 expression may be a useful prognostic molecular marker for patients with advanced ovarian cancer. FAU - Kusuda, Tomoyo AU - Kusuda T AD - Department of Obstetrics and Gynecology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. FAU - Shigemasa, Kazushi AU - Shigemasa K FAU - Arihiro, Koji AU - Arihiro K FAU - Fujii, Tsuneo AU - Fujii T FAU - Nagai, Nobutaka AU - Nagai N FAU - Ohama, Koso AU - Ohama K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (DNA, Complementary) RN - 0 (Interleukin-12 Subunit p40) RN - 0 (Interleukin-6) RN - 0 (Protein Subunits) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Cystadenocarcinoma, Serous/genetics/metabolism/pathology MH - DNA, Complementary/genetics/metabolism MH - Female MH - Humans MH - Interferon-gamma/genetics/metabolism MH - Interleukin-10/genetics/metabolism MH - Interleukin-12/genetics/metabolism MH - Interleukin-12 Subunit p40 MH - Interleukin-6/genetics/metabolism MH - Neoplasms, Glandular and Epithelial/genetics/*metabolism/pathology MH - Ovarian Neoplasms/genetics/*metabolism/pathology MH - Ovary/metabolism/pathology MH - Prognosis MH - Protein Subunits/genetics/metabolism MH - RNA, Messenger/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Th1 Cells/*metabolism MH - Th2 Cells/*metabolism MH - Tumor Necrosis Factor-alpha/genetics/metabolism EDAT- 2005/05/05 09:00 MHDA- 2005/09/20 09:00 CRDT- 2005/05/05 09:00 PHST- 2005/05/05 09:00 [pubmed] PHST- 2005/09/20 09:00 [medline] PHST- 2005/05/05 09:00 [entrez] PST - ppublish SO - Oncol Rep. 2005 Jun;13(6):1153-8.