Both the 5th and 6th editions of TNM staging system fail to independently predict long-term prognosis after radical hepatectomy in hepatocellular carcinoma sized > or = 5 cm.

OBJECTIVE: To validate the predictive power of the 5th and 6th editions of TNM staging system (TNM-5, TNM-6) in a Chinese patient cohort with hepatocellular carcinoma (HCC) sized > or = 5 cm after radical hepatectomy. METHODS: Consecutive 121 patients with HCC sized > or = 5 cm undergoing radical hepatectomy between January 1995 and December 2002 were included. The impact of clinicopathological variables on prognosis was determined by univariate and multivariate analyses, after excluding 2 perioperative deaths. RESULTS: In univariate analysis, TNM-5 stage did not show prognostic significance for overall or disease-free survival, as opposed to TNM-6 stage, Edmondson-Steiner grade, portal vein tumor thrombosis (PVTT), vascular invasion, satellite nodule, Child-Pugh grade, and hepatitis B surface antigen (HBsAg) positivity. When these significant variables were entered in multivariate analysis, Edmondson-Steiner grade was the sole independent prognosticator for both overall and disease-free survival, whereas Child-Pugh grade independently influenced disease-free survival. However, TNM-6 stage lost its predictive potential in multivariate analysis. CONCLUSIONS: Neither TNM-5 nor TNM-6 staging system is revealed to be independently prognostic in patients with HCC sized > or = 5 cm after radical hepatectomy. Therefore, TNM-6 calls for more support in many subsets of HCC patients.

Edmondson-Steiner grading increases the predictive efficiency of TNM staging for long-term survival of patients with hepatocellular carcinoma after curative resection.

BACKGROUND: The 6th edition TNM staging (TNM-6) for hepatocellular carcinoma (HCC) has been recommended. However, its superiority, in contrast to the previous 5th edition (TNM-5), has not been fully recognized. Besides, tumor differentiation was not included. The current study was designed to compare the value of these two staging systems and, more importantly, to elucidate whether Edmondson-Steiner grading, a well-acknowledged histological classification, is helpful in further discriminating different prognosis of HCC. METHODS: Prospectively collected clinicopathological and follow-up data of consecutive 171 patients with HCC undergoing curative hepatic resection (CHR) were reviewed retrospectively. The impacts of variables on survival were determined by univariate and multivariate statistical analyses. RESULTS: The differences of survival between stages of the TNM-6 and TNM-5 were almost significant, except for disease-free survival for TNM-5. Moreover, TNM-6 might be a more powerful prognostic predictor compared with TNM-5, although their impacts on survival were all not independent, unlike Edmondson-Steiner grading. For patients with each stage of TNM-6, Edmondson-Steiner grade was the sole significant variable in both univariate and multivariate analyses. Finally, a novel scoring criteria (prognostic scoring for CHR, PSCHR) integrating Edmondson-Steiner grading and TNM-6 was attempted and statistically shown to be of independent significance and stronger predicting value for prognosis of curatively resected HCC. CONCLUSION: TNM-6 revealed to be more significantly prognostic than TNM-5 in patients with HCC after curative hepatic resection. Edmondson-Steiner grading could raise the predictive efficiency of TNM-6 for postresectional survival of patients with HCC. Therefore, PSCHR containing Edmondson-Steiner grading was preliminarily proposed.

Structure analysis and expressions of a novel tetratransmembrane protein, lysosoma-associated protein transmembrane 4 beta associated with hepatocellular carcinoma.

AIM: To analyze the structure and expressions of the protein encoded by an HCC-associated novel gene, lysosome-associated protein transmembrane 4 beta (LAPTM4B). METHODS: Primary structure and fundamental characteristics of LAPTM4B protein were analysed with bioinformatics. Expressions of LAPTM4B in HCC tissues and various cell lines were detected using polyclonal antibodies and Western blot. RESULTS: LAPTM4B encoded two isoforms of proteins with molecular masses 35-ku and 24-ku, respectively. The expression level of LAPTM4B-35 protein in HCC tissues was dramatically upregulated and related to the differentiation status of HCC tissues, and it was also high in some cancer cell lines. Computer analysis showed LAPTM4B was an integral membrane protein with four transmembrane domains. LAPTM4B showed relatively high homology to LAPTM4A and LAPTM5 in various species. CONCLUSION: LAPTM4B gene encoded two isoforms of tetratransmembrane proteins, LAPTM4B-35 and LAPTM4B-24. The expression of LAPTM4B-35 protein is upregulated and associated with poor differentiation in human HCC tissues, and also at high levels in some cancer cell lines. LAPTM4B is an original and conserved protein.

Molecular cloning and characterization of LAPTM4B, a novel gene upregulated in hepatocellular carcinoma.

Lysosomal-associated protein transmembrane-4 beta (LAPTM4B), a novel gene upregulated in hepatocellular carcinoma (HCC), was cloned using fluorescence differential display, RACE, and RT-PCR. It contains seven exons and encodes a 35-kDa protein with four putative transmembrane regions. Both the N- and C-termini of the protein are proline-rich, and may serve as potential ligands for the SH3 domain. Immunohistochemical analysis localized the protein predominantly to intracellular membranes. Northern blot showed that the LAPTM4B mRNAs were remarkably upregulated in HCC (87.3%) and correlated inversely with differentiation status. LAPTM4B was also overexpressed in many HCC-derived cell lines. It was also highly expressed in fetal livers and certain adult normal tissues including the heart, skeletal muscle, testis, and ovary. Promoter function assays showed a distinct difference in the gene's activities between BEL7402 and HLE cell lines, suggesting that the transcription factors responsible for regulation of the gene in the two cell lines are different, and that possible negative regulatory cis-elements may exist upstream of the promoter region. It was demonstrated that the N-terminus of LAPTM4B was essential for survival of the cells. Cells harboring the full-length LAPTM4B cDNA expression clone displayed a slightly increased efficiency in colony formation. These results suggest that LAPTM4B is a potential protooncogene, whose overexpression is involved in carcinogenesis and progression of HCC. In normal cells, it may also play important roles such as regulation of cell proliferation and survival.