TY - JOUR
T1 - Gene expression in fixed tissues and outcome in hepatocellular carcinoma
AU - Hoshida, Yujin
AU - Villanueva, Augusto
AU - Kobayashi, Masahiro
AU - Peix, Judit
AU - Chiang, Derek Y.
AU - Camargo, Amy
AU - Gupta, Supriya
AU - Moore, Jamie
AU - Wrobel, Matthew J.
AU - Lerner, Jim
AU - Reich, Michael
AU - Chan, Jennifer A.
AU - Glickman, Jonathan N.
AU - Ikeda, Kenji
AU - Hashimoto, Masaji
AU - Watanabe, Goro
AU - Daidone, Maria G.
AU - Roayaie, Sasan
AU - Schwartz, Myron
AU - Thung, Swan
AU - Salvesen, Helga B.
AU - Gabriel, Stacey
AU - Mazzaferro, Vincenzo
AU - Bruix, Jordi
AU - Friedman, Scott L.
AU - Kumada, Hiromitsu
AU - Llovet, Josep M.
AU - Golub, Todd R.
PY - 2008/11/6
Y1 - 2008/11/6
N2 - Background: It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue. Methods: We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival. Results: The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P = 0.04). Conclusions: We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma.
AB - Background: It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue. Methods: We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival. Results: The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P = 0.04). Conclusions: We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma.
UR - http://www.scopus.com/inward/record.url?scp=57349090407&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa0804525
DO - 10.1056/NEJMoa0804525
M3 - Article
AN - SCOPUS:57349090407
SN - 0028-4793
VL - 359
SP - 1995
EP - 2004
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 19
ER -