Genotyping of hepatocellular carcinoma in liver transplant recipients adds predictive power for determining recurrence-free survival

Marsh, J. Wallis; Finkelstein, Sydney; Demetris, Anthony J.; Swalsky, Patricia A.; Sasatomi, Eizaburo; Bandos, Andriy I.; Subotin, Michael; Dvorchik, Igor

doi:10.1053/jlts.2003.50144

Cited by 119 publications

(98 citation statements)

References 36 publications

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“…For this reason, the standard criteria for LT for HCC are the Milan criteria: patients within the Milan criteria had acceptable or far better 5-year DFS of more than 80% whereas patients beyond the Milan criteria had around 50% 5-year DFS. To expand the criteria for LT for HCC further, more detailed selection criteria representing tumor biology [22, 33, 34] and more aggressive pretransplant neoadjuvant therapy for downstaging [35, 36] would be required as well as a more generous philosophy of acceptance of a 5-year DFS of around 50%.…”

Section: High Cost and Lifelong Immunosuppression For Ltmentioning

confidence: 99%

Current Role of Surgery in Treatment of Early Stage Hepatocellular Carcinoma: Resection versus Liver Transplantation

Suh²,

Kim

et al. 2008

Oncology

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Hepatocellular carcinoma (HCC) is the most common malignancy of the liver and is most commonly associated with hepatitis B infection in Korea. Although liver resection is regarded as a potentially curative treatment option, it is only feasible in less than 20% of patients. The reason for this is that HCC arises in cirrhotic livers and is often multicentric. Liver transplantation (LT) which could be used in the treatment both of the tumor and background liver seems to be a rational approach for early stage patients with decompensated liver cirrhosis. Current good selection criteria of LT for HCC are the Milan criteria: 1 HCC nodule ≤5 cm in diameter or 3 nodules ≤3 cm. By restricting LT to patients within the Milan criteria, the 4-year disease-free survival rate was more than 80%, which is comparable to that of a transplant candidate without HCC. However, there are serious limitations for the wider application of LT for HCC: (1) organ shortage, (2) risk to a live donor, (3) high cost, and (4) lifelong immunosuppression. For this reason, for a patient with early stage HCC and with Child A cirrhosis in whom partial hepatectomy is possible, the choice of primary treatment with curative intent is still under debate.

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Section: High Cost and Lifelong Immunosuppression For Ltmentioning

confidence: 99%

Current Role of Surgery in Treatment of Early Stage Hepatocellular Carcinoma: Resection versus Liver Transplantation

Suh²,

Kim

et al. 2008

Oncology

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“…A vast amount of information regarding genetic markers and genomic aberrations, as well as gene expression, is being accumulated for the study of HCC (9)(10)(11)(12)(13)(14)(15). The major risk factors for HCC development are now well defined, and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years (16,17).…”

Section: Introductionmentioning

confidence: 99%

Genes Involved in Viral Carcinogenesis and Tumor Initiation in Hepatitis C Virus-Induced Hepatocellular Carcinoma

Mas

Maluf

Archer

et al. 2009

Mol Med

256

236

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The role of chronic hepatitis C virus (HCV) in the pathogenesis of HCV-associated hepatocellular carcinoma (HCC) remains controversial. To understand the transition from benign to malignant, we studied the gene expression patterns in liver tissues at different stages, including normal, cirrhosis, and different HCC stages. We studied 108 liver tissue samples obtained from 88 distinct patients (41 HCV-cirrhotic tissues, 17 HCV-cirrhotic tissues from patients with HCC, and 47 HCV-HCC tissues). Differentially expressed genes (DEG) were studied by use of high-density oligonucleotide arrays. Among probe sets identified as differentially expressed via the F test, all pairwise comparisons were performed. Cirrhotic tissues with and without concomitant HCC were further evaluated, and a classifier was used to predict whether the tissue type was associated with HCC. Differential expression profiles were analyzed using Interaction Networks and Functional Analysis. Characteristic gene signatures were identified when normal tissue was compared with cirrhosis, cirrhosis with early HCC, and normal with HCC. Pathway analysis classified the cellular and biological functions of the DEG as related to cellular growth and proliferation, cell death and inflammatory disease in cirrhosis; cell death, cell cycle, DNA replication, and immune response in early HCCs; and cell death, cell growth and proliferation, cell cycle, and DNA repair in advanced HCCs. Characteristic gene signatures were identified at different stages of HCV-HCC progression. A set of genes were identified to predict whether the cirrhotic tissue was associated with HCC.

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“…Moreover, there is no agreement on the selection criteria that could simultaneously maximize the number of viable HCC candidates for transplantation and reject the smallest number of those who could have benefited (34)(35)(36). Molecular genetic analyses have shown that genomic changes accumulate during the development and progression of HCC (37)(38)(39)(40). Establishment of a molecularbased method for the classification of HCV-HCC pretransplantation will permit the detection of distinct subgroups of HCC patients with different prognoses, allowing greater accuracy in selection of patients for treatment cure with transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…Recent developments in biomedical technology enable us to detect tumor cells at a molecular level (41,42). Molecular/biologic information is beginning to be incorporated into current staging systems to better predict HCC recurrence (37,43,44). An important question is whether molecular staging will be able to augment the accuracy by which the prognosis of individual patients can be assessed.…”

Section: Discussionmentioning

confidence: 99%

Differentially Expressed Genes between Early and Advanced Hepatocellular Carcinoma (HCC) as a Potential Tool for Selecting Liver Transplant Recipients

Mas

Maluf

Archer

et al. 2006

Mol Med

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Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Liver transplantation (LT) represents a curative treatment for "small" HCC. Preoperative staging is critical in selecting optimal candidates for LT to optimize the use of this scarce resource. From December 1997 to February 2004, 148 patients diagnosed with cirrhosis and HCC were evaluated at our center. After staging, the patients were listed for LT according to United Network for Organ Sharing (UNOS) criteria. When pretransplant liver MRIs were compared with the findings of the explanted livers, 8 of 35 patients (22.8%) were understaged. Three of the 8 patients (37.5%) had recurrence post-LT. A retrospective gene expression profiling study was done using microarray technology for tumor samples in the pretransplant hepatitis C virus (HCV)-HCC understaged patients and in a contemporaneous group of HCV-HCC patients that were accurately staged. Two sample t tests comparing the early versus advanced HCV-HCCs with respect to gene expression showed an important set of genes differentially expressed among the samples. Hierarchical clustering analysis of the gene expression profiling classified 93.8% of the total tumor samples and 85.7% of the understaged samples in concordance with the explanted pathological staging. We found a distinctive pattern of gene expression between early and advanced HCV-HCCs. These results suggest that gene expression profiling could improve the pre-LT HCC staging to more closely mimic the explant pathology. Whether gene expression profiling of HCC will be refined to the point of predicting potential metastatic biologic behavior to predict post-LT recurrence will require longitudinal prospective study of this gene array technology.

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Genotyping of hepatocellular carcinoma in liver transplant recipients adds predictive power for determining recurrence-free survival

Cited by 119 publications

References 36 publications

Current Role of Surgery in Treatment of Early Stage Hepatocellular Carcinoma: Resection versus Liver Transplantation

Current Role of Surgery in Treatment of Early Stage Hepatocellular Carcinoma: Resection versus Liver Transplantation

Genes Involved in Viral Carcinogenesis and Tumor Initiation in Hepatitis C Virus-Induced Hepatocellular Carcinoma

Differentially Expressed Genes between Early and Advanced Hepatocellular Carcinoma (HCC) as a Potential Tool for Selecting Liver Transplant Recipients

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