Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P52742 (pT3)
 1,034 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cumulative recurrence after surgical resection for hepatocellular carcinoma (HCC) is very high. Several retrospective analyses have shown that liver transplantation was more effective than resection for patients with HCC at early tumor stages. Consequently, in January 1990, we decided to prospectively indicate orthotopic liver transplantation (OLT) as the first surgical treatment for small, localized HCC in cirrhotic patients without nodal involvement independently of the degree of liver function. The aim of this prospective cohort study was to analyze prognosis, recurrence rate, and survival after liver transplantation in patients in whom the main indication was HCC with cirrhosis. Thirty-eight patients in whom the main indication for liver transplantation was HCC and hepatic cirrhosis were compared with 136 transplantations because of cirrhosis without tumor, performed in our unit from January 1990 to December 1995. HCC arising in noncirrhotic livers and those incidently discovered after OLT were excluded from the study. Chemoembolization using doxorubicin, lipiodol, and Gelfoam was performed before OLT in 31 patients with good liver function. There were no differences in gender, but HCC patients were older (57 +/- 7 vs. 50 +/- 10 years [P < .001]). Liver function was better in HCC (Child-Pugh score: 6.9 +/- 2 vs. 8.6 +/- 1.8; P < .001), and hepatitis C virus antibody was positive in 31 (82%) vs. 51 (37%) (P < .007). Seven tumors had bilobar involvement (18%). Capsule was present in 22 (58%). The mean size of the tumor was 3.4 +/- 2 cm. Seventeen tumors (45%) were larger than 3 cm, and 4 (11%) were larger than 5 cm. The average number of nodules was 2 +/- 1. The tumor-node-metastasis stage of the tumors was pT1 in 6 patients (16%), 11 were pT2 (29%), 12 were pT3 (31%), and 9 were pT4 (24%). Seven patients were retransplanted in the HCC group (18%) and 19 (14%) in the nontumor group (not significant). Tumor recurrence was detected in three patients (8%). One, 3-, and 5-year survival rates were 82% vs. 79%, 75% vs. 71%, and 63% vs. 68%, respectively, for patients with and without HCC, and no differences were found between the two groups (P = .84). Survival was significantly reduced in patients with a macroscopic vascular invasion and tumors greater than 5 cm in diameter. Recurrence and mortality after liver transplantation in cirrhotic patients with carefully selected HCC are similar to the results in cirrhotic patients without tumor.
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PMID:Survival after liver transplantation in cirrhotic patients with and without hepatocellular carcinoma: a comparative study. 918 72

Epigenetic silencing of tumour suppressor genes has been observed in various cancers. Looking at hepatocellular carcinoma (HCC) specific protein silencing was previously demonstrated to be associated with the Hepatitis C virus (HCV). However, the proposed HCV dependent promoter methylation of DNA mismatch repair (MMR) genes and thereby enhanced progression of hepatocarcinogenesis has been the subject of controversial discussion. We investigated promoter methylation pattern of the MMR genes MLH1, MSH2 and PMS2 as well as the cyclin-dependent kinase inhibitor 2A gene (p16) in 61 well characterized patients with HCCs associated with HCV, Hepatitis B virus infection or alcoholic liver disease. DNA was isolated from formalin-fixed, paraffin-embedded tumour and non-tumour adjacent tissue and analysed by methylation-specific PCR. Moreover, microsatellite analysis was performed in tissues showing methylation in MMR gene promoters. Our data demonstrated that promoter methylation of MLH1, MSH2, PMS2 and p16 is present among all considered HCCs. Hereby, promoter silencing was detectable more frequently in advanced-stage HCCs than in low-stage ones. However, there was no significant correlation between aberrant DNA methylation of MMR genes or p16 and HCV infection in related HCC specimens. In summary, we show that promoter methylation of essential MMR genes and p16 is detectable in HCCs most dominantly in pT3 stage tumour cases. Since loss of MMR proteins was previously described to be not only responsible for tumour development but also for chemotherapy resistance, the knowledge of mechanisms jointly responsible for HCC progression might enable significant improvement of individual HCC therapy in the future.
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PMID:Promoter methylation of MLH1, PMS2, MSH2 and p16 is a phenomenon of advanced-stage HCCs. 2440 91