[Relationship between genetic alterations and clinicopathological features in intrahepatic cholangiocarcinoma].
OBJECTIVE
To evaluate the pedigree of genetic alterations during the tumorigenesis of intrahepatic cholangiocarcinoma (ICC) and their correlation with clinicopathological features by analysis of loss of heterozygosity (LOH) in 6 tumor suppressor genes (APC, MCC, DCC, OGG1, p53 and RB1) and point mutations in Ki-ras-2 oncogene.


METHODS
Genomic DNA was isolated from paraffin-embedded slides of 22 surgically resected ICC cases by microdissection-based PCR amplification and agarose gel electrophoresis. Genetic alterations were analyzed by direct DNA sequencing.


RESULTS
The total frequency of alterations in 7 genes studied was 86.4% (19/22). Based on the pattern of altered genes and their correlation with clinicopathological parameters, the genetic alterations were classified into two groups: Group I (9/19, 47.4%): alterations in APC, MCC, DCC and Ki-ras-2,); Group II (10/19, 52.6%): alterations in p53, OGG1 and RB1. The average age of patients in Group I (mean age, 57.2 years) was significantly younger than those in Group II (mean age, 69.1 years) (P < 0.05).


CONCLUSIONS
The occurrence and development of ICC was closely related with the accumulation and cooperation of multiple genetic alterations. The genetic alterations of APC, MCC, DCC and Ki-ras-2 may play crucial roles in the early stage of development of ICC, and the genetic alterations of p53, OGG1 and RB1 may play important roles in accelerating advanced progression of ICC. The detection of the pedigree of genetic alterations in ICC may provide useful information for evaluating the state of tumor progression and clinic prognosis.
Cong
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W
Department of Pathology, Oriental Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China. wmcong@smmu.edu.cn
Finkelstein
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SD
Wu
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D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D017491:Genes, APC; D016163:Genes, DCC; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017354:Point Mutation; D015996:Survival Rate