Fractional allelic imbalance could allow for the development of an equitable transplant selection policy for patients with hepatocellular carcinoma.
Liver transplantation (LT) in the presence of hepatocellular carcinoma (HCC) remains a controversial issue because the current staging systems are not sufficiently predictive of outcomes. Paraffin blocks from 183 patients that underwent LT in the presence of HCC were collected. Molecular analysis was carried out blindly on the native liver specimens in all cases with respect to recurrence outcomes. The fractional allelic imbalance (FAI) rate index was determined in each case and was used to compare the acquired mutational load between different tumors. The FAI was determined from the microdissected tissue site displaying the greatest amount of acquired allelic loss. FAI was found to be the strongest predictor of recurrence followed by vascular invasion and then by tumor number or hepatic lobar involvement. Based on these findings, 3 prognostic models were constructed for selection of candidates for LT in patients with concomitant HCC. Molecular markers of tumor progression are the strongest predictors of HCC recurrence currently available, surpassing all components of the tumor-node-metastasis classification system for staging of malignant tumors (TNM), including vascular invasion. Incorporation of these molecular markers of tumor progression could help resolve the ongoing conundrum of organ allocation for patients with HCC.
Dvorchik
Igor
I
Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-3236, USA.
Schwartz
Myron
M
Fiel
M Isabel
MI
Finkelstein
Sydney D
SD
Marsh
J Wallis
JW
D000293:Adolescent; D000328:Adult; D000368:Aged; D022981:Allelic Imbalance / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D016031:Liver Transplantation; D018895:Microsatellite Repeats; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018579:Patient Selection