Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 21, 2006; 12(27): 4338-4344
Published online Jul 21, 2006. doi: 10.3748/wjg.v12.i27.4338
Amplification of D22S283 as a favorable prognostic indicator in liver fluke related cholangiocarcinoma
Jongkonnee Thanasai, Temduang Limpaiboon, Patcharee Jearanaikoon, Vajarabhongsa Bhudhisawasdi, Narong Khuntikeo, Banchob Sripa, Masanao Miwa
Jongkonnee Thanasai, Graduate School, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand
Temduang Limpaiboon, Patcharee Jearanaikoon, Department of Clinical Chemistry, Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
Vajarabhongsa Bhudhisawasdi, Narong Khuntikeo, Department of Surgery, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Banchob Sripa, Department of Pathology, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Masanao Miwa, Department of Biochemistry and Molecular Oncology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 3058575, Japan
Supported by The Thailand Research Fund through The Royal Golden Jubilee PhD Program, Grant No. PHD/0037/2544 for Thanasai J and Limpaiboon T
Correspondence to: Dr. Temduang Limpaiboon, Department of Clinical Chemistry, Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand. temduang@kku.ac.th
Telephone: +66-43-362028 Fax: +66-43-202088
Received: March 1, 2006
Revised: March 10, 2006
Accepted: March 21, 2006
Published online: July 21, 2006
Abstract

AIM: To analyze the DNA copy number of target genes NF2, TIMP3, ST13, TOB2, BIK, and TP and the reference microsatellite markers D22S283, D22S423, and D22S274 mapped on 22q12-qter in liver fluke related cholangiocarcinoma (CCA) and define its correlation with clinical parameters.

METHODS: Quantitative real time PCR (qPCR) was used for determining allelic imbalances in 65 liver fluke related CCA tissues. Statistical correlations between allelic imbalances and clinicopathological parameters, i.e. age, sex, tumor stage, histological type, blood vessel invasion, nerve invasion and lymphatic invasion were evaluated by means of the χ2 test. Cox regression analysis was used for determining patient’s survival.

RESULTS: Amplifications of the TP (22q13.33), TOB2 (22q13.2-13.31), D22S283 (22q12.3), TIMP3 (22q12.3) and NF2 (22q12.2) were found in 35 (53.8%), 28 (43.1%), 27 (41.5%), 24 (36.9%), and 24 (36.9%), respectively. Losses at the D22S423 (22q13.1-13.2) and BIK (22q13.31) were detected in 26 (40%) and 23 (35.4%), respectively. Significant correlations were observed between lymphatic invasion and allelic losses of BIK (P = 0.025) and D22S283 (P = 0.041). Univariate and multivariate Cox regression analysis revealed D22S283 amplification as an independent predictor of good prognosis (P = 0.006, death hazard ratio = 0.411, 95% CI = 0.217-0.779) and blood vessel invasion as an independent poor prognostic factor (P = 0.042, death hazard ratio = 1.911, 95% CI = 1.022-3.571) in CCA patients.

CONCLUSION: This study provides evidence for the involvement of gene amplification and deletion on chromosome 22q in liver fluke related CCA. This is the first report of D22S283 amplification as an independent indicator of favorable prognosis in liver fluke related CCA.

Keywords: Liver fluke related cholangiocarcinoma; Chromosome 22q; D22S283; Allelic imbalance; Quantitative real time PCR