Research advances in multifocal hepatocellular carcinoma / 中华肝胆外科杂志

Based on the pathogenetic occurrence of the tumor,multinodular hepatocellular carcinoma can be classified into multicentric occurrence and intrahepatic metastasis.Different diagnostic strategies from genomics,transcriptomics and proteomics can be used to define the clonal origin of tumors and provide advisable method to cure the disease.Pathomorphological test wasgold standard in cancer diagnosis at one time.Currently,from the respect of molecular diagnosis,including HBV DNA intergration,p53 mutation,selective X chromosome inactivation,loss of heteozygosity of chromosomal DNA,mtDNA-Loop,transcriptional sequence,and comparative proteomics,we could accurately differentiate the clonal origin of tumors.Intrahepatic metastasis was demonstrated with a high early recurrence rate and low survival rate comparing to the multicentric occurrence from the review of the previous study.

Role of the 1-month protocol transarterial chemoinfusion in detecting intrahepatic metastasis after resection of large hepatocellular carcinoma greater than 10 cm

BACKGROUNDS/AIMS: Tumor recurrence is very common after hepatic resection of hepatocellular carcinoma (HCC) > or =10 cm. The purpose of this study was to validate the prognostic significance of the preoperative alkaline phosphatase (ALP) level and early intrahepatic metastasis in HCC patients who underwent resection of large HCC. METHODS: Clinical data of 100 large HCC patients who underwent liver resection were retrospectively reviewed. All of them underwent protocol transarterial chemoinfusion (TACI) at 1 month. RESULTS: Median tumor diameter was 13.8 cm, and 94% were single lesions. Systematic and non-systematic resections were performed in 91% and 9%, respectively, with R0 resection achieved in 84%. Overall 1-, 3- and 5-year survival rates were 76%, 38.5%, and 30.4%, respectively. Univariate analyses on patient survival revealed that intrahepatic metastasis on 1-month protocol TACI was the only significant risk factor (p=0.002). Mean ALP values according to the intrahepatic metastasis on 1-month protocol TACI were 124.6+/-76.9 IU/L and 145.1+/-92.6 IU/L, which did not show a statistical difference (p=0.23). CONCLUSIONS: In patients with large HCC, 1-month protocol TACI combined with hepatic resection may contribute to the early detection and timely treatment of potentially preexisting metastatic lesions.

Clonal origin of hepatocellular carcinoma: Recent progress / 第二军医大学学报

Multinolular and intrahepatic recurrent HCC can originate from intrahepatic metastasis and multiple origins, and their colnal origin is closely related to the clinical diagnosis and treatment. To designate suitable therapeutic strategies according to their colnal origin is a new challenge needs to be tackled urgently. This paper reviews recent progress in the clinicopathological features, molecular diagnosis and clinical outcomes of multiple origin HCC.

Clonality analysis for differentiating multicentric origin and intrahepatic metastasis in multiple hepatocellular carcinomas / 中华肝胆外科杂志

Objective To explore the differential diagnostic significance of clone analysis for multicentric occurrence (MO) and intrahepatic metastasis (IM) in hepatocellular carcinomas (HCCs).Methods Loss of heterozygosity (LOH) and microsatellite instability (MSI) were analyzed by microsatellite polymorphism test and the integration sites of HBV were assessed by Southern blot in each nodule of the HCCs. The clonalities were then compared between each nodule of the same patient and the diagnosis of MO or IM was concluded. Finally, the results based on clonality analysis were compared with those according to clinicopathological and imaging data. Results According to the results of LOH and MSI in 79 nodules and nontumorous tissue from 35 cases of mutiple HCCs, 5 (14.3%)and 29 cases (82.9 %) were divided into MO and IM, respectively. Both MO and IM presented simultaneously in 1 patient (2.9%). The integration sites of HBV could be analyzed in 77 nodules from 34 multiple HCCs. Among them, 6 (17. 6%) and 27 cases (79.4%) were divided into MO and IM, respectively. Both MO and IM presented simultaneously in 1 patient (2.9%). The classification results of microsatellite polymorphism test and HBV integration sites analysis demonstrated a significant positive correlation (rs = 0.909, P＜0.001). Nevertheless, neither the classification of microsatellite polymorphism test nor that of HBV integrate sites analysis was correlated with the discrimination according to clinicopathologic and imaging data (rs=0. 133, P=0. 468, rs =0. 262, P=0. 155, respectively). Recurrence in patients in the MO group occurred significantly later than that in IM cases who were diagnosed by clonality analyses (P=0. 001). Conclusion The clonality analysis based on the results of LOH and MSI or assessments of HBV integrate sites is useful for the differential diagnosis of MO and IM and their treatment and prognosis.

The Clinical Significance of Expression of Matrix Metalloproteinase in Hepatocellular Carcinoma

PURPOSE: A hepatocellular carcinoma is an epithelial cancer, originating from hepatocytes, and frequently shows early invasion into blood vessels, with intrahepatic metastasis. Matrix metalloproteinases (MMPs) are endogenous peptidases capable of degrading various components of basement membranes. The ability of malignant epithelial cells to degrade extracellular matrices and basement membranes are important steps in the metastatic invasion process, and it is necessary for cancer cells to acquire this cleavage ability in order to become invasive. METHODS: To evaluate the clinical significance of the expressions of MMPs in hepatocellular carcinomas, twenty-five patients with hepatocellular carcinomas (HCC group), and twelve patients with normal livers (control group), were enrolled in this study between July 2001 and July 2002. RESULTS: The expression of MMP-9 was significantly elevated in the HCC group (80.3+/-9.4) compared with that of the control group (54.7+/-5.6) (P5 cm), vascular invasion and capsular infiltration were significantly higher than in those without these clinical manifestations (P<0.05). There was no significant correlation between MMP-9 expression and liver cirrhosis or histological type. CONCLUSION: The present study shows a close relationship between the expression of MMP-9 and capsular infiltration, vessel invasion and tumor stage in HCC. MMP-9 may be used as a prognostic marker and for the development of strategies for the treatment modality in HCC.

The Clinical Significance of Expression of Matrix Metalloproteinase in Hepatocellular Carcinoma

PURPOSE: A hepatocellular carcinoma is an epithelial cancer, originating from hepatocytes, and frequently shows early invasion into blood vessels, with intrahepatic metastasis. Matrix metalloproteinases (MMPs) are endogenous peptidases capable of degrading various components of basement membranes. The ability of malignant epithelial cells to degrade extracellular matrices and basement membranes are important steps in the metastatic invasion process, and it is necessary for cancer cells to acquire this cleavage ability in order to become invasive. METHODS: To evaluate the clinical significance of the expressions of MMPs in hepatocellular carcinomas, twenty-five patients with hepatocellular carcinomas (HCC group), and twelve patients with normal livers (control group), were enrolled in this study between July 2001 and July 2002. RESULTS: The expression of MMP-9 was significantly elevated in the HCC group (80.3+/-9.4) compared with that of the control group (54.7+/-5.6) (P5 cm), vascular invasion and capsular infiltration were significantly higher than in those without these clinical manifestations (P<0.05). There was no significant correlation between MMP-9 expression and liver cirrhosis or histological type. CONCLUSION: The present study shows a close relationship between the expression of MMP-9 and capsular infiltration, vessel invasion and tumor stage in HCC. MMP-9 may be used as a prognostic marker and for the development of strategies for the treatment modality in HCC.

Study of Genomic Heterogeneity of Hepatocellular Carcinomas by Using Arbitrary Primer Polymerase Chain Reaction (AP-PCR) / 한국간담췌외과학회지

BACKGROUND/AIMS: Discrimination between intrahepatic metastasis (IM) and de novo multicentric occurrence (MO) in multiple hepatocellular carcinoma (HCC) is important not only for the study of hepatocarcinogenesis but also for determination of therapeutic strategies. The purpose of this study is to evaluate the clonality of multiple or recurrent hepatocelluar carcinoma by using AP-PCR. METHODS: Paraffin-embedded blocks of 9 multiple synchronous hepatocellular carcinomas, one recurrent hepatocellular carcinoma and one combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma were used. None of the tumors was larger than 3.3 cm in diameter. Microdissection was done by using sterile 27 gauge needles and microscope. Two different arbitrary primers (AR3, ZF3) were utilized in AP- PCR. The clonality of tumor was assessed by DNA band pattern (DNA fingerprint) of PCR product. RESULTS: Eight of nine multiple synchronous hepatocellular carcinomas had distinctly different DNA fingerprints. One recurrent hepatocellular carcinoma and one combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma also had different DNA fingerprints. CONCLUSION: AP-PCR is a simple and very powerful method for determining the clonality of multiple hepatocellular carcinomas. The majority of multiple, small-sized hepatocellular carcinomas have different clonalities and it seems that a significant number of multiple hepatocellular carcinomas are of multicentric, de novo nature.

Clonal origin of hepatocellular carcinoma:recent progress / 第二军医大学学报

Multinolular and intrahepatic recurrent HCC can originate from intrahepatic metastasis and multiple origins,and their colnal origin is closely related to the clinical diagnosis and treatment.To designate suitable therapeutic strategies according to their colnal origin is a new challenge needs to be tackled urgently.This paper reviews recent progress in the clinicopathological features,molecular diagnosis and clinical outcomes of multiple origin HCC.