TY - JOUR
T1 - Microdissection-based allelotyping discriminates de novo tumor from intrahepatic spread in hepatocellular carcinoma
AU - Finkelstein, Sydney D.
AU - Marsh, Wallis
AU - Demetris, Anthony J.
AU - Swalsky, Patricia A.
AU - Sasatomi, Eizaburo
AU - Bonham, Andrew
AU - Subotin, Michael
AU - Dvorchik, Igor
N1 - Funding Information:
Abbreviations: HCC, hepatocellular carcinoma; LOH, loss of heterozygosity; FAL, fractional allelic loss; TNM, tumor-node-metastasis. From the 1Departments of Pathology and Laboratory Medicine, 2Transplantation Surgery, and 3Biostatistics Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA. Received July 16, 2002; accepted January 9, 2003. Supported by a grant from The Pittsburgh Foundation, funded by The R. Green Annan Medical Fund, the William J. Black Fund, the Simeon M. Jones, Jr. and Katharine Reed Jones Fund, the Anna E. McElhaney Fund, and the Benjamin H. and Portia T. Hosler Fund. Address reprint requests to: Sydney D. Finkelstein, M.D., Department of Pathology, University of Pittsburgh Medical Center, 200 Lothrop St., PUH A610.2, Pittsburgh, PA 15213. E-mail: finkelsteinsd@msx.upmc.edu; fax: 412-647-6251. Copyright © 2003 by the American Association for the Study of Liver Diseases. 0270-9139/03/3704-0021$30.00/0 doi:10.1053/jhep.2003.50134
PY - 2003/4/1
Y1 - 2003/4/1
N2 - A total of 103 cases of hepatocellular carcinoma (HCC) arising in native livers discovered at the time of transplantation underwent allelic loss analysis. HCC mutational allelotyping targeted 10 genomic loci (1p, 3p, 5q, 7q, 8q, 9p, 10q, 17p, 17q, 18q) using 18 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes associated with human carcinogenesis. Gene analysis was performed on microdissected tissue samples removed from 4-μm thick histologic sections at specific topographic sites selected on the basis of representative cellular characteristics. Microdissection targets included largest tumor nodule at 2 locations as well as up to 3 additional tumor nodules in each case. HCC genotyping characteristics including mutational profile and cumulative fractional allelic loss (FAL) were correlated with clinical and pathologic features. Individual nodules of HCC showed 2 patterns of mutational change: (1) essentially concordant mutational profiles consistent with intrahepatic spread of tumor, or (2) discordant mutational profiles consistent with independent primary cancer formation. In 15 of 56 cases (27%) in which the HCC was in a multinodular, bilobar form (T4), sufficient discordance in the allelic loss profile enabled a more accurate T-stage classification with better prediction of recurrence-free survival. In conclusion, microdissection genotyping of HCC is an effective and objective means to (1) distinguish between de novo HCC tumor formation versus intrahepatic spread of cancer and to (2) improve on current methods for prediction of tumor aggressiveness and recurrence-free survival after liver transplantation.
AB - A total of 103 cases of hepatocellular carcinoma (HCC) arising in native livers discovered at the time of transplantation underwent allelic loss analysis. HCC mutational allelotyping targeted 10 genomic loci (1p, 3p, 5q, 7q, 8q, 9p, 10q, 17p, 17q, 18q) using 18 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes associated with human carcinogenesis. Gene analysis was performed on microdissected tissue samples removed from 4-μm thick histologic sections at specific topographic sites selected on the basis of representative cellular characteristics. Microdissection targets included largest tumor nodule at 2 locations as well as up to 3 additional tumor nodules in each case. HCC genotyping characteristics including mutational profile and cumulative fractional allelic loss (FAL) were correlated with clinical and pathologic features. Individual nodules of HCC showed 2 patterns of mutational change: (1) essentially concordant mutational profiles consistent with intrahepatic spread of tumor, or (2) discordant mutational profiles consistent with independent primary cancer formation. In 15 of 56 cases (27%) in which the HCC was in a multinodular, bilobar form (T4), sufficient discordance in the allelic loss profile enabled a more accurate T-stage classification with better prediction of recurrence-free survival. In conclusion, microdissection genotyping of HCC is an effective and objective means to (1) distinguish between de novo HCC tumor formation versus intrahepatic spread of cancer and to (2) improve on current methods for prediction of tumor aggressiveness and recurrence-free survival after liver transplantation.
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U2 - 10.1053/jhep.2003.50134
DO - 10.1053/jhep.2003.50134
M3 - Article
C2 - 12668980
AN - SCOPUS:0037381623
SN - 0270-9139
VL - 37
SP - 871
EP - 879
JO - Hepatology
JF - Hepatology
IS - 4
ER -