Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Microsatellite alterations in patients with intrahepatic cholangiocarcinoma

T Limpaiboon PhD 1, K Krissadarak 1, B Sripa 2, P Jearanaikoon PhD 1, V Bhudhisawasdi MD 3, S Chua-in MD 3, A Romphruck MSc 4, C Pairojkul MD 2

1 Dept Clinical Chemistry, Faculty of Associated Medical Sciences, Khon Kaen University,, 2 Dept Pathology,, 3 Surgery and, 4 Blood Tranfusion Center, Faculty of Medicine; Khon Kaen University, Khon Kaen, Thailand,,

AIM: Cholangiocarcinoma is a common hepatobiliary malignancy with highest incidence in Northeast Thailand. In spite of many epidemiological and experimental studies, the mechanism of cholangiocarcinogenesis is still unclear. It has been known that genetic alterations of genes are involved in cancer development. Three classes of genes causing cancer predisposition are oncogenes, tumor suppressor genes, and DNA repair genes. However, the knowledge of genes implicated in cholangiocarcinoma is very limited. This study, therefore, attempted to determine loss of heterozygosity (LOH) and microsatellite instability (MSI) of DNA mismatch repair genes hMSH2 and hMLH1 and tumor suppressor gene p53 using PCR based microsatellite markers D2S119, D3S1611, and TP53, respectively. METHODS: MSI and LOH were studied in 55 patients with intrahepatic cholangiocarcinoma. DNA derived from leukocytes, microdissected tumor and non-tumor tissues of each patient were PCR amplified at loci D2S119, D3S1611, and TP53. MSI and LOH were analyzed by GS 2000 Gel-scan fragment analyzer. RESULTS: Of 55 samples, 11(20%) demonstrated MSI at D2S119 and 4(7%) showed MSI at D3S1611. No MSI were found at TP53 locus. Of 55 patients studied, information for microsatelitte markers D3S1611 and TP53 were 36 and 50 cases, respectively. LOH were shown in 7 out of 36 (19%) informative cases for D3S1611 and 16 out of 50 (32%) for TP53. No LOH were detected at D2S119 locus. Of 55 cases evaluated for MSI, 13 (23.6%) showed MSI at one locus (D2S119 or D3S1611) and 2 (3.6%) demonstrated MSI at two loci. Twenty seven (49%) of the 55 cases demonstrated microsatellite alterations (MSI or LOH) in at least one locus. No association between histologic types and genetic alterations of each locus was found. CONCLUSION: This study suggests that genetic alterations of DNA mismatch repair genes and tumor suppressor gene p53 may be involved in cholangiocarcinogenesis and these alterations may be of value in cancer diagnosis and prognosis.

KEY WORDS: Molecular pathology, opisthorchiasis, bile duct cancer.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on genetic instability.