Replication error frequencies in primary hepatocellular carcinoma: a comparison of solitary primary versus multiple primary cancers.
OBJECTIVE
Replication errors (RERs) at microsatellite loci are associated with the development of not only hereditary nonpolyposis colon cancer but also sporadic cancers. To examine the association between RERs and human hepatocarcinogenesis, we looked for microsatellite instability in solitary and multiple primary hepatocellular carcinomas (HCCs).


METHODS
DNAs were extracted from 34 solitary primary HCCs and 14 HCCs with multiple primary cancers. Twelve microsatellite alleles were amplified by PCR from the DNAs, and RERs were assessed by their mobility shift.


RESULTS
RERs were found in only two cases (6%) of solitary HCC and four cases (29%) of HCC with multiple primary cancers. Two of the four HCCs with multiple primary cancers showed RERs at two and three microsatellite loci, respectively. Of 12 microsatellite loci examined, TP53 and D16S476 sensitively detected RERs in HCCs with multiple primary cancers, at a frequency of 23% and 33%, respectively.


CONCLUSIONS
RERs are rarely associated with carcinogenesis in human primary HCC, and RER-related genetic alterations may be associated with a part of HCC with multiple primary cancers. If future studies confirm this association, then the two probes TP53 and D16S476 may be useful for the prediction of development of multiple primary cancers with HCC.
First Department of Pathology, Nihon University School of Medicine, Tokyo, Japan.
K
K
Takagi
M
M
Esumi
S
S
Takano
S
S
Iwai
D000293:Adolescent; D000328:Adult; D000368:Aged; D020137:Base Pair Mismatch; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D004261:DNA Replication; D004276:DNA, Satellite / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology; D011995:Recombination, Genetic
D004276:DNA, Satellite; D005819:Genetic Markers