Genetic alterations and growth pattern in biliary duct carcinomas: loss of heterozygosity at chromosome 5q bears a close relation with polypoid growth.
Biliary duct carcinomas (BDCs) are relatively rare and the carcinogenic mechanisms underlying their induction are poorly understood. There are two growth patterns, polypoid and non-polypoid infiltrative type, but little information is available concerning the relation between growth pattern and genetic alterations. A comparative study was therefore conducted to clarify if differences in genetic changes, including loss of heterozygosity (LOH) at 5q, 9p, 17p, and 18q, and K-ras mutations exist between polypoid and non-polypoid infiltrative type BDCs. LOH analysis was performed using microsatellite markers and K-ras point mutations were analysed by dot blot hybridisation. The incidences of changes for polypoid and non-polypoid infiltrative types were 73% and 26% on 5q, 63% and 59% on 9p, 55% and 50% on 17p, and 20% and 18% on 18q, and 25% and 27% for K-ras mutations. Most importantly, we found the frequency of 5qLOH to be significantly higher with polypoid growth than in the non-polypoid infiltrative type (p<0.05), especially in extrahepatic duct carcinomas (p<0.05). The incidences of other genetic alterations (LOH at 9p, 17p, and 18q, and K-ras mutations) showed similar rates with both tumour types. The present data suggest that 5qLOH may have a close relation with polypoid growth in BDCs.
Hidaka
E
E
Department of Pathology, Cancer Institute, Tokyo, Japan.
Yanagisawa
A
A
Seki
M
M
Setoguchi
T
T
Kato
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000235:genetics*; D017734:Bile Ducts, Extrahepatic; D001653:Bile Ducts, Intrahepatic; D002277:Carcinoma / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D017491:Genes, APC / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000235:genetics; D019942:Genes, p16 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction