Patterns of methylation profiles as diagnostic markers for multiple hepatocellular carcinomas.
BACKGROUND
Hepatocellular carcinoma often displays multiple tumor nodules, thus posing a problem for differential diagnosis between cancers of both multifocal and metastatic origin. Conventionally, pathological criteria have been used for this purpose, but these are largely subjective. In order to facilitate a more objective differential diagnosis of multiple HCCs, we used the patterns of methylation of p16INK4a, p14ARF, and GSTP1 genes as markers for each tumor nodule.


METHODS
Sixty-seven nodules from 30 cases of multiple or recurrent HCCs were examined using methylation-specific PCR (MSP) analysis for the detection of methylation profiles.


RESULTS
Hypermethylation was detected in 56.7%, 43.3% and 17.9% of the cases for p16INK4a, p14ARF, and GSTP1 genes, respectively. At the genetic level the inter-nodule methylation profiles were heterogeneous in 23 of the cases and homogeneous in another 7, enabling a multifocal origin to be diagnosed in the former and metastatic origin in the latter.


CONCLUSIONS
Methylation profiling seems to be useful in differentiating the clonal origins of multiple cancers, as the information yielded by this method is essentially objective.
Anzola
M
M
Dept. de Z. y Dinámica Celular, Facultad de Farmacia, Universidad del País Vasco, Vitoria, Spain.
Cuevas
N
N
López-Martínez
M
M
Martínez de Pancorbo
M
M
Burgos
J J
JJ
D000217:Acyltransferases / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D019942:Genes, p16 / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism*
D025803:Tumor Suppressor Protein p14ARF; D000217:Acyltransferases; C043403:fatty acyl ethyl ester synthase