ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Carcinoma, Hepatocellular , Cholangiocarcinoma , Discrimination, Psychological , DNA , DNA Fingerprinting , Microdissection , Needles , Neoplasm Metastasis , Polymerase Chain Reaction , Population CharacteristicsABSTRACT
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.