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Objective: To investigate the clinicopathological features, treatment, and prognosis of hepatic angiosarcoma. Methods: Clinicopathological data and prognostic conditions of 18 cases with hepatic angiosarcoma were collected retrospectively. The recurrence-free survival rate and overall survival rate were calculated by the Kaplan-Meier method. A Cox regression analysis was used to explore the survival-related risk factors. Results: There were 12 male and 6 female patients, with an average age of 57 (37 ~ 70) years. The tumor's average diameter was 8.40 (2.00 ~ 18.00) cm. Seven cases had multiple tumors, while two cases had large vessel tumor thrombuses. Microscopically, the tumor tissues were irregularly anastomosed, with vascular lacunar or solid bundle-like weaving, and the tissue morphology mimicked capillary hemangioma, cavernous hemangioma, or angioepithelioma, while tumor cells were spindle-shaped or epithelioid, lined with hobnails in the lumen, or formed papillary structures in the lumen. The proportion of highly, moderately, and poorly differentiated tumors was 4:8:6, with six cases having clear tumor boundaries, eight having microvascular tumor thrombi, and sixteen having blood lake formation. Different levels of expression of CD31, CD34, erythroblast transformation-specific related genes, and Fli-1 markers were demonstrated in all of the cases. Four cases had a P53 mutation, and six cases had Ki-67 > 10%. During the follow-up period of 0.23-114.20 months, the five-year recurrence-free survival rate and overall survival rate were 16.7% and 37.2%, respectively. Cox regression multivariate analysis showed that preoperative symptoms and multiple tumors were significant risk factors for recurrence-free survival, while preoperative symptoms and Ki-67 > 10% were significant risk factors for overall survival. Conclusion: Hepatic angiosarcoma is a rare hepatic mesenchymal tumor with high malignancy and a poor prognosis. Pathological morphology and immunohistochemical marker combinations are needed for a definite diagnosis. However, the complexity of angiosarcomas' histological and cytological conformations and the overlap of pathological features with benign vascular tumors, sarcomas, and carcinomas pose difficulties in the differential diagnosis. Thus, the only effective ways to prolong survival are early detection and radical surgical resection.
Subject(s)
Humans , Male , Female , Middle Aged , Hemangiosarcoma , Ki-67 Antigen , Retrospective Studies , Biomarkers, Tumor/metabolism , Prognosis , Liver Neoplasms/pathologyABSTRACT
Copy number aberrations (CNAs) in chromosome arm 8q have been associated with unfavorable clinical outcomes of several cancers and progressive tumor characteristics of hepatocellular carcinoma (HCC).This study was to identify correlation of CNAs in 8q with clinical outcomes of HCC patients,and further screen for differentially expressed genes in outcome-related CNAs.Array comparative genomic hybridization and expression arrays were performed to detect CNAs and expression levels,respectively.The correlations between CNAs in 8q and outcomes were analyzed in 66 patients,with a median follow-up time of 45.0 months (range,2.6-108.6 months).One hundred and nine cases were further evaluated to identify differentially expressed genes in the potential outcome-related CNAs.Copy number gain in 8q was observed in 22 (33.3 %) of the 66 HCC cases.The most recurrent gains (with frequencies >20%) were 8q13.3-21.3,8q21.3-23.3,8q23.3-24.13,8q24.13-24.3,and 8q24.3.Survival analysis showed that 8q24.13-24.3 gain was significantly associated with reduced overall survival (P=0.010).Multivariate Cox analysis identified 8q24.13-24.3 gain as an independent prognostic factor for poor overall survival (HR=2.47;95%CI=1.16-5.26;P=0.019).A panel of 17 genes within the 8q24.13-24.3 region,including ATAD2,SQLE,PVT1,ASAP1,and NDRG1 were significantly upregulated in HCCs with 8q24.13-24.3 gain compared to those without.These results suggest that copy number gain at 8q24.13-24.3 is an unfavorable prognostic marker for HCC patients,and the potential oncogenes ATAD2,SQLE,PVT1,ASAP1,and NDRG1 within the regional gain,may contribute coordinately to the 8q24.13-24.3 gain-related poor prognosis.
ABSTRACT
Copy number aberrations (CNAs) in chromosome arm 8q have been associated with unfavorable clinical outcomes of several cancers and progressive tumor characteristics of hepatocellular carcinoma (HCC).This study was to identify correlation of CNAs in 8q with clinical outcomes of HCC patients,and further screen for differentially expressed genes in outcome-related CNAs.Array comparative genomic hybridization and expression arrays were performed to detect CNAs and expression levels,respectively.The correlations between CNAs in 8q and outcomes were analyzed in 66 patients,with a median follow-up time of 45.0 months (range,2.6-108.6 months).One hundred and nine cases were further evaluated to identify differentially expressed genes in the potential outcome-related CNAs.Copy number gain in 8q was observed in 22 (33.3 %) of the 66 HCC cases.The most recurrent gains (with frequencies >20%) were 8q13.3-21.3,8q21.3-23.3,8q23.3-24.13,8q24.13-24.3,and 8q24.3.Survival analysis showed that 8q24.13-24.3 gain was significantly associated with reduced overall survival (P=0.010).Multivariate Cox analysis identified 8q24.13-24.3 gain as an independent prognostic factor for poor overall survival (HR=2.47;95%CI=1.16-5.26;P=0.019).A panel of 17 genes within the 8q24.13-24.3 region,including ATAD2,SQLE,PVT1,ASAP1,and NDRG1 were significantly upregulated in HCCs with 8q24.13-24.3 gain compared to those without.These results suggest that copy number gain at 8q24.13-24.3 is an unfavorable prognostic marker for HCC patients,and the potential oncogenes ATAD2,SQLE,PVT1,ASAP1,and NDRG1 within the regional gain,may contribute coordinately to the 8q24.13-24.3 gain-related poor prognosis.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the clinicopathological features and prognosis of primary hepatic lymphoma (PHL).</p><p><b>METHODS</b>Thirty-five patients with PHL who underwent surgical resection and were confirmed by pathology in our hospital from 1982 to 2012 were re-evaluated for clinicopathological data, including their symptoms, radiological features, recurrence interval, histopathological properties and prognosis.</p><p><b>RESULTS</b>Of the 35 patients, 25 were men (71.4%) and 10 were women (28.6%), with an average age of 52.6 years old (range, 17-79 years). Presented symptoms were epigastric phymatosis, abdominal pain and low-grade fever. In the present study, 21 (60.0%) patients were positive for HBsAg, 1(2.9%) patient was positive for anti-HCV, 3 patients were positive for AFP, 12 patients and 2 patients were complicated by cirrhosis and hepatocellular carcinoma, respectively. Pathologically, 35 PHL were classified into 19 DLBCL (54.3%), 13 T cell-lymphoma (37.1%), and 3 MALT lymphoma (8.6%). Patients with DCBCL showed better postoperative survival than patients with T cell-lymphoma (31.7 ± 3.2) months vs. (22.9 ± 2.2) months (P < 0.05).</p><p><b>CONCLUSIONS</b>Hepatitis B virus (HBV) infection may contribute to the pathogenesis of Chinese patients with PHL. Surgical resection followed by comprehensive therapy is the first-line option for PHL. The prognosis of patients with PHL is associated with PHL subtypes.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antigens, CD20 , Metabolism , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Carcinoma, Hepatocellular , Pathology , Therapeutics , Virology , Chemotherapy, Adjuvant , Cyclophosphamide , Therapeutic Uses , Doxorubicin , Therapeutic Uses , Follow-Up Studies , Hepatitis B , Hepatitis B Surface Antigens , Metabolism , Hepatitis C Antibodies , Metabolism , Leukocyte Common Antigens , Metabolism , Liver Cirrhosis , Liver Neoplasms , Pathology , Therapeutics , Virology , Lymphoma , Pathology , Therapeutics , Virology , Lymphoma, B-Cell, Marginal Zone , Pathology , Therapeutics , Virology , Lymphoma, Large B-Cell, Diffuse , Pathology , Therapeutics , Virology , Lymphoma, T-Cell , Pathology , Therapeutics , Virology , Prednisone , Therapeutic Uses , Retrospective Studies , Survival Rate , Vincristine , Therapeutic Uses , alpha-Fetoproteins , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To review and investigate the optimal preoperative diagnostic means and treatment principles of hepatic angiomyolipoma (HAML).</p><p><b>METHODS</b>The clinical features, treatment, prognostic and follow-up data of 169 HAML patients treated between January 1992 and May 2010 were retrospectively analyzed. The median age of the patients, including 46 male and 123 female (male/female, 1/2.7), was 45 years (range, 17 - 73 years). The mean case history was 0.54 year with a range of 2 d to 16 years.</p><p><b>RESULTS</b>Among the 169 patients, 149 patients (88.2%) had a solitary tumor and 96 patients (56.8%) were detected in the right lobe. The overall preoperative diagnostic rate was 13.6% and 119 patients (70.4%) were misdiagnosed as hepatocellular carcinoma or hepatic cavernous hemangioma. The diagnostic accuracy of MRI is higher than CT in distinguishing the nature of the tumor (χ² = 5.508, P = 0.019). One hundred and sixty-eight patients received surgical resection and one received percutaneous microwave coagulation therapy. One patient occurred postoperative hemorrhage and 3 patients developed hydrothorax. The postoperative mortality and recurrence for all the patients were 0. Postoperative pathology confirmed the diagnosis of hepatic angiomyolipoma. Follow-up study showed a benign course and no signs of recurrence.</p><p><b>CONCLUSIONS</b>MRI is the main diagnostic means of HAML. Treatment strategies of HAML depends largely on tumor size, location and growth rate. Surgical management is suggested to patients with the following criteria: (1) tumor size greater than 5 cm; (2) with clinical symptoms; (3) faster tumor growth; (4) the tumor located at 1, 4, 5, 8 segments of liver.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Angiomyolipoma , Diagnosis , General Surgery , Follow-Up Studies , Hepatectomy , Liver Neoplasms , Diagnosis , General Surgery , Magnetic Resonance Imaging , Prognosis , Retrospective StudiesABSTRACT
<p><b>OBJECTIVE</b>To approach the biopathological features of hilar cholangiocarcinoma and surgical pathological factors which influence the long-term survivals of patients with hilar cholangiocarcinoma.</p><p><b>METHODS</b>A systemic and retrospective multi-parameter analysis was performed on 205 patients of hilar cholangiocarcinoma who received surgical treatments and had complete clinicopathological data as well as follow-up results during a ten-year-period from April 1998 to April 2008. The single factor analysis was performed on age, sex, content of pre-operative serum CA19-9, Child-pugh grading, TNM classification, operation pattern, resection margin status of bile duct, vascular invasion, adjacent liver involvement, grade differentiation, infiltration-depth of bile duct, lymph node metastasis and perineural infiltration. A multivariate analysis was performed through Cox proportional hazard model.</p><p><b>RESULTS</b>The single factor analysis showed that except age, sex and content of pre-operative serum CA19-9, the mainly significant factors influencing the survivals were Child-Pugh grading, TNM classification, operation pattern, bile duct margin, vascular invasion, adjacent liver involvement, grade differentiation, infiltrating-depth of bile duct, lymph node metastasis and perineural infiltration (P < 0.05). Lymph node metastasis and infiltration-depth of bile duct wall were found to be the two independent factors influencing overall survival by multivariate analysis through the Cox model.</p><p><b>CONCLUSIONS</b>The most important prognostic factors influencing the long-term survivals of patients with hilar cholangiocarcinoma after operation are lymph node metastasis and depth of tumor-infiltrating of involved bile duct. During the operation, standardized evaluation through frozen section should be carried out for detection of lymph node metastasis and depth of tumor-infiltrating of involved bile ducts, which can be used as the histological indicator for surgical expansion, and could be helpful to maximize avoiding the tumor cell residues and therefore, to improve the long-term effects of surgical resection.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Bile Duct Neoplasms , Pathology , General Surgery , Bile Ducts, Intrahepatic , Cholangiocarcinoma , Pathology , General Surgery , Follow-Up Studies , Hepatectomy , Lymphatic Metastasis , Pathology , Neoplasm Invasiveness , Pathology , Prognosis , Proportional Hazards Models , Retrospective Studies , Survival AnalysisABSTRACT
<p><b>OBJECTIVE</b>To investigate the possible association between the single nucleotide polymorphisms (SNPs) (C-8343G, C-1863T and R72P) in TP53 gene and susceptibility to liver metastases of colorectal cancer (CRC) in a Chinese population.</p><p><b>METHODS</b>The genotypes of each SNP in TP53 gene were determined by either TaqMan assays or PCR-based restriction fragment length polymorphism (RFLP) method in 121 colorectal cancer patients with liver metastases and sex-, age-matched 280 cases with nonmetastatic CRC as a control. Immunohistochemical staining for P53 was performed on paraffin-embedded sections. Odds ratios (ORs) for colorectal liver metastases and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks.</p><p><b>RESULTS</b>No significant association of C-8343G or C-1863T with colorectal liver metastases risk was observed. However, the R allele of the TP53 R72P polymorphism was more frequently found in metastatic cases than in nonmetastatic cases (P= 0.037). When compared with PP homozygotes, the ORs of metastases for RP heterozygotes was 2.21 (95% CI: 1.13-4.33), for RR homozygotes was 2.26 (95% CI: 1.03-4.94), and for carriers of the 72R allele (RP or RR genotype) was 2.22 (95% CI: 1.16-4.26). Stratified analysis indicated that carrying the 72R allele had a more pronounced increase in colorectal liver metastases risk among patients with positive P53 expression tumors (OR= 3.28, 95% CI: 1.21-8.88), whereas no significantly increased metastases risk was found in patients with negative P53 expression tumors (OR= 1.37, 95% CI: 0.52-3.62).</p><p><b>CONCLUSION</b>The R allele of the TP53 R72P polymorphism may contribute to the etiology of liver metastases in CRC patients, particularly among those with positive P53 expression tumors. Both TP53 C-8343G and C-1863T may be not associated with colorectal liver metastases risk.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Colorectal Neoplasms , Genetics , Genes, p53 , Genetics , Genetic Predisposition to Disease , Genetics , Genotype , Liver Neoplasms , Genetics , Polymerase Chain Reaction , Polymorphism, Genetic , Genetics , Polymorphism, Restriction Fragment Length , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the possible association of the MTHFR C677T polymorphism with genetic susceptibility to hepatocellular carcinoma (HCC) in a Chinese population.</p><p><b>METHODS</b>Five hundred and eight HCC cases and 543 controls were studied. The MTHFR genotypes were determined using a PCR-based restriction fragment length polymorphism (RFLP) method. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate relative risks. Potential HCC risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotypes and HCC risks.</p><p><b>RESULTS</b>No overall significant difference in genotype distribution was found when comparing all HCC cases to controls (P = 0.258). However, a significantly increased risk of HCC was observed among T/T homozygotes (adjusted OR = 1.66, 95% CI = 1.08-2.54, P<0.05) compared to C-allele carriers (CC or CT). When stratified with sex, this trend was more prominent in females, but not in males. Females who were homozygous (T/T) for the C677T polymorphism were at a 2.64-fold (95% CI = 1.19-5.88, P<0.05) increased risk of developing HCC when compared to C-allele carriers. However in males, T/T homozygotes had a similar risk with C-allele carriers.</p><p><b>CONCLUSION</b>The MTHFR C677T polymorphism may be associated with a higher HCC risk in females, but not in males in this population.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Carcinoma, Hepatocellular , Genetics , Genetic Predisposition to Disease , Liver Neoplasms , Genetics , Logistic Models , Methylenetetrahydrofolate Reductase (NADPH2) , Genetics , Polymorphism, GeneticABSTRACT
<p><b>OBJECTIVE</b>To summarize the Chinese experience in pathologic diagnosis of liver biopsies after orthotopic liver transplantation (OLTx).</p><p><b>METHODS</b>1123 post-transplant liver biopsies from 665 OLTx patients from the Shanghai Eastern Hepatobiliary Surgery Hospital, Tianjin First Central Hospital, Guangzhou Sun Yat-sen University and Chongqing Southwest Hospital were retrospectively analyzed. All liver biopsies were stained with hematoxylin and eosin. Immunohistochemical studies for cytomegalovirus, HBsAg, CK19, CD4 and CD8 were also performed in selected examples.</p><p><b>RESULTS</b>In the involved hospitals, 4 to 12 types of complications were encountered after OLTx. The number of liver biopsies performed for each patient ranged from 1 to 9 (mean = 2.2). The timing of these biopsies varied from the second to the 2877 th post-transplant day. The 5 most common complications were acute cellular rejection (35.6%), ischemic-reperfusion injury (13.4%), biliary stricture (5.6%), drug complication (5.0%) and chronic rejection (4.7%). The 5 earliest complications after OLTx were primary non-function (occurring at day 4.7 +/- 2.1), ischemic-reperfusion injury (occurring at day 14.0 +/- 4.0), acute cellular rejection (occurring at day 32.1 +/- 62.9), hepatic artery thrombosis / stricture (occurring at day 62.9 +/- 74.2) and cytomegalovirus infection (occurring at day 107.7 +/- 93.0).</p><p><b>CONCLUSIONS</b>This study has evaluated the types, incidence and timing of major complications occurring after OLTx. The most important issue is the distinction between rejection and non-rejection pathology. Thorough understanding of atypical pathologic features of these complications is necessary. The Banff Schema (rejection activity index) for grading liver allograft rejection is useful for monitoring anti-rejection therapy and should be used routinely.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Biopsy, Needle , Cholestasis, Intrahepatic , Pathology , Graft Rejection , Pathology , Hepatic Artery , Pathology , Liver Transplantation , Pathology , Postoperative Complications , Pathology , Reperfusion Injury , Pathology , Retrospective Studies , Thrombosis , PathologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of different treatments for hepatocellular carcinoma (HCC) with tumor thrombus in the portal vein (PVTT).</p><p><b>METHODS</b>From Jan. 2000 to Jan. 2003, a total of 84 HCC patients with PVTT were divided into five groups based on methed of treatment: Group A (n = 9), HCC resection + PVTT removal + postoperative TACE + thymosin alpha(1); Group B (n = 20), HCC resection + PVTT removal + postoperative TACE; Group C (n = 7), HCC resection + PVTT removal; Group D (n = 38), TACE only; Group E (n = 10), conservative treatment only.</p><p><b>RESULTS</b>The rate of PVTT shrinkage or disappearance of groups A, B, C, D and E was 66.7%, 70.0%, 57.1%, 7.9% and 0, respectively with respective median survival time of 10.0, 7.0, 8.0, 5.0 and 2.0 months. The one year survival rate was 44.4%, 15.0%, 14.3%, 10.5% and 0.</p><p><b>CONCLUSION</b>Resection of HCC and removal of tumor thrombus in the portal vein may have the tumor thrombus cleared in most of the patients and postoperative TACE and thymisin alpha(1) treatment may improve their survival.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Hepatocellular , Mortality , General Surgery , Therapeutics , Chemoembolization, Therapeutic , Combined Modality Therapy , Follow-Up Studies , Hepatectomy , Methods , Hepatic Artery , Liver Neoplasms , Mortality , General Surgery , Therapeutics , Neoplastic Cells, Circulating , Pathology , Portal Vein , Pathology , Survival Analysis , Thymosin , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of postoperative anti-viral therapy using lamivudine and thymosin alpha1 on recurrence of hepatocellular carcinoma (HCC) coexisting with active hepatitis B.</p><p><b>METHODS</b>From Jan. 2000 to Dec. 2002, 33 HCC patients with coexisting with active hepatitis B were randomized into two groups: Group I (n = 17) received hepatectomy only, and Group II (n = 16) received hepatectomy and postoperative therapy using lamivudine plus thymosin alpha1. The suppression of HBV-DNA, HBeAg seroconversion rate, tumor recurrence rate and median survival in the two groups were observed and compared.</p><p><b>RESULTS</b>In Group II and Group I, the 1-year HBV-DNA suppression rate was 100.0% vs 6.0% (P < 0.01), HBeAg seroconversion rate was 62.5% vs 5.9% (P < 0.05), tumor recurrence rate was 81.3% vs 95.5% (P > 0.05), the recurrence time was 7.0 vs 5.0 months (P < 0.01) and median survival 10.0 vs 7.0 months (P < 0.01).</p><p><b>CONCLUSION</b>Anti-viral therapy using lamivudine and thymosin alpha1 postoperatively may suppress the HBV reaction, delay the recurrence and prolong the survival for patients with HCC with coexisting active hepatitis B.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Carcinoma, Hepatocellular , General Surgery , Therapeutics , Virology , DNA, Viral , Hepatectomy , Methods , Hepatitis B , Genetics , Therapeutics , Lamivudine , Therapeutic Uses , Liver Neoplasms , General Surgery , Therapeutics , Virology , Neoplasm Recurrence, Local , Postoperative Period , Reverse Transcriptase Inhibitors , Therapeutic Uses , Survival Rate , Thymosin , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>A functional single nucleotide polymorphism (SNP) at codon 72 of the gene for p53 protein (p53 R72P) has been implicated in a variety of human cancers, but the relationship between this SNP and hepatocellular carcinoma (HCC) remains obscure despite the fact that the critical role of p53 protein in HCC has been documented. This study was conducted to evaluate the link between the polymorphism with HCC stratified by chronic hepatitis B infection status in a Chinese population.</p><p><b>METHODS</b>Four hundred and sixty-nine HCC cases (359 HbsAg-positive, 110 HbsAg-negative) and 567 controls (137 HbsAg-positive, 430 HbsAg-negative) were studied. The p53 genotypes were determined by a PCR based restriction fragment length polymorphism (RFLP) method.</p><p><b>RESULTS</b>Overall, no correlation between HCC and the R72P genotypes was found when comparing all cases to controls or when comparing the HbsAg-positive HCC subgroup to controls. However, in HbsAg-negative subjects, the 72P allele was significantly associated with the presence of HCC (P=0.01) and had a higher risk (OR=1.69, 95% CI: 1.25-2.27) of HCC as compared to the 72R allele. By comparison to R/R homozygotes, the R/P heterozygotes and P/P homozygotes had a 1.73-fold (95% CI: 0.96-3.11) and a 3.29-fold (95% CI: 1.58-6.86) increased risk for HCC, respectively. The subjects with the 72P allele and a family history of HCC and those with the 72P allele and male gender also yielded an 11.14-fold (95% CI: 1.62-76.67) and a 9.39 fold (95% CI: 3.08-28.62) increased risk of HCC, respectively.</p><p><b>CONCLUSION</b>The P allele of the p53 R72P polymorphism has an increased risk for HCC in HbsAg-negative subjects, and exerts a synergistic influence on the risk for HCC when combined with HCC family history and the male gender.</p>
Subject(s)
Female , Humans , Male , Asian People , Genetics , Carcinoma, Hepatocellular , Ethnology , Genetics , China , Codon , Genetics , Gene Frequency , Genetic Predisposition to Disease , Genetics , Genotype , Linkage Disequilibrium , Liver Neoplasms , Ethnology , Genetics , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Tumor Suppressor Protein p53 , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of loss of heterozygosity (LOH) in tumor suppressor genes (TSG) and microsatellite instability (MSI) in hepatocarcinogenesis, as well as their correlation with clinicopathologic features.</p><p><b>METHODS</b>LOH in 6 TSG (APC, DCC, MCC, OGG1, p53 and RB1) was detected in 36 informative cases of hepatocellular carcinoma (HCC), among 92 surgically resected HCC. Thirteen polymorphic microsatellite markers were also studied in 15 of these cases by microdissection-based PCR amplification and direct DNA sequencing. The correlation between genetic alterations and clinicopathologic features was analyzed.</p><p><b>RESULTS</b>The overall incidence of LOH in HCC was 41.7% (15/36). There was no LOH in MCC gene. 46.2% (6/13) microsatellites showed LOH in 9 of the 15 cases of HCC (60%). Certain clinicopathologic differences were observed between cases (number = 7) with LOH in APC, OGG1 and DCC ("type I") and cases (number = 8) with LOH in p53 and RB1 ("type II"). The mean tumor size of these two types was 2.9 (+/- 1.7) cm and 7.2 (+/- 3.4) cm, respectively (P < 0.01); and the mean survival was 72.0 (+/- 38.6) months, and 51.0 (+/- 30.4) months, respectively (P < 0.05).</p><p><b>CONCLUSIONS</b>Compared with MSI pathway, LOH pathway plays a more important role in the development of HCC. A multistep hepatocarcinogenesis is likely, with LOH in APC, OGG1 and DCC ("type I") being an early event and LOH in p53 and RB1 ("type II") being a late event. On the other hand, MCC gene seems to play no role in the whole process.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Infant , Male , Middle Aged , Carcinoma, Hepatocellular , Genetics , Pathology , Genes, APC , Genes, DCC , Genes, MCC , Genes, Tumor Suppressor , Genes, p53 , Liver Neoplasms , Genetics , Pathology , Loss of Heterozygosity , Microsatellite InstabilityABSTRACT
<p><b>OBJECTIVE</b>To study the features of micro satellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Ten high-polymorphic micro satellite markers on chromosome 4 were selected to be detected for loss of heterozygosity (LOH), micro satellite instability (MSI) and allelic imbalance (AI) in 56 HCC using PCR-simple sequence length polymorphism (PCR-SSLP) analysis.</p><p><b>RESULTS</b>LOH was found in 40 of 56 HCC (71.4%) on at least 1 locus, the top two loci were D4S426 (61%), D4S1534 (53.7%). LOH on D4S406 was significantly higher in cases with positive serum HBsAg than in those with negative HBsAg. Similarly, LOH on D4S1538 occurred more frequently in patients with HBsAg negative than those with HBsAg positive [76.9% (20/26) vs 12.5% (2/16), chi2=13.999, P<0.01]. LOH on D4S426, D4S1615 and D4S165 were more frequent in poorly or moderately differentiated HCC than in well-differentiated HCC [76.7%(23/30) vs 18.2%(2/11), chi2=9.242, P<0.01; 53.8% (14/26) vs 16.7% (2/12), P<0.05; 60.7% (17/28) vs 18.2% (2/11), P<0.01]. LOH on loci D4S2921 was more frequently detected in tumors with intrahepatic metastasis than in those without [63.6% (21/33) vs 18.2% (2/11), chi2=5.132, P<0.01]. MSI was found in 8.9% (5/56) cases. AI was found in 26.8% (15/56) of all cases examined.</p><p><b>CONCLUSION</b>Frequent micro satellite alterations on chromosome 4 were existed in HCC. LOH, which represents tumor suppressor gene pathway, plays a more important role in hepatocarcinogenesis of HCC; MSI, representing mismatch repair gene pathway, arranges as the next.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Carcinoma, Hepatocellular , Genetics , Chromosomes, Human, Pair 4 , Liver Neoplasms , Genetics , Loss of Heterozygosity , Microsatellite RepeatsABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of postoperative transcatheter hepatic arterial chemoembolization (TACE) and thymosin alpha(1) (T(alpha1)) treatment on recurrence of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>From Jan 2000 to Dec 2002, 57 patients with HCC were randomly divided into three groups: group A (n = 18) received hepatectomy plus postoperative TACE and T(alpha1), group B (n = 23) received hepatectomy plus postoperative TACE and group C (n = 16) received hepatectomy only. The recurrence rate, the time to tumor recurrence and the median survival for the three groups were investigated.</p><p><b>RESULTS</b>For group A, B and C, the 1 year recurrence rate was 83.3%, 87.0% and 87.5% (P = 0.926), respectively. The time to tumor recurrence was 7.0, 5.0 and 4.0 months (P = 0.039), respectively. The median survival was 10.0, 7.0 and 8.0 months (P = 0.002), respectively.</p><p><b>CONCLUSION</b>Postoperative TACE plus Talpha(1) treatment for HCC patients does not decrease the recurrence rate but may delay its occurrence and prolong surviving time.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adjuvants, Immunologic , Antibiotics, Antineoplastic , Antineoplastic Agents , Carboplatin , Carcinoma, Hepatocellular , General Surgery , Therapeutics , Chemoembolization, Therapeutic , Doxorubicin , Hepatectomy , Iodized Oil , Liver Neoplasms , General Surgery , Therapeutics , Mitomycin , Neoplasm Recurrence, Local , Postoperative Period , Survival Rate , ThymosinABSTRACT
<p><b>OBJECTIVE</b>To study the clinicopathological characteristics, immunohistochemical features and differential diagnosis of hepatic angiomyolipoma (AML).</p><p><b>METHODS</b>The clinicopathological features of hepatic AML were systematically examined in 44 surgically resected tumor specimens, with additional immunohistochemistry study using 10 relevant antibodies.</p><p><b>RESULTS</b>The tumors were composed of various amounts of three components, i.e. blood vessels, smooth muscle cells and adipose cells. According to the proportions of each of these tissue components, AML was subcategorized into the classical type (n = 13), myomatous type (n = 25), lipomatous type (n = 4), and angiomatous type (n = 2). Myoid cells displayed various morphology, including epithelioid, intermediate (ovoid or short spindle), spindle, oncocytic, and pleomorphic features. Hematopoietic elements were present as minor findings in eight tumors. Immunohistochemically, the tumor cells were strongly positive for HMB45 (44/44, 100%), SMA (38/38, 100%) and CD117 (30/38, 78.9%).</p><p><b>CONCLUSIONS</b>A correct diagnosis of hepatic AML might be difficult due to its various growth patterns and cell types. HMB-45 positivity in the myoid cells is a key feature for hepatic AML. CD117 may be another useful ancillary marker for reaching a definite diagnosis.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Angiomyolipoma , Classification , Allergy and Immunology , Pathology , Antigens, Neoplasm , Biomarkers, Tumor , Diagnosis, Differential , Follow-Up Studies , Immunohistochemistry , Liver , Pathology , Liver Neoplasms , Classification , Allergy and Immunology , Pathology , Melanoma-Specific Antigens , Neoplasm Proteins , Proto-Oncogene Proteins c-kitABSTRACT
<p><b>OBJECTIVE</b>To study the features of microsatellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Ten high-polymorphic microsatellite markers on chromosome 8 were selected to detect the loss of heterozygosity (LOH), microsatellite instability (MSI) and allelic imbalance (AI) in 56 HCCs using automatic capillary array electrophoresis DNA analysis system.</p><p><b>RESULTS</b>LOH was found in 37 of 56 HCCs (66.1%) on at least 10 locus. The three most frequently altered loci were D8S261 (53.5%, 23/43), D8S1721 (52.5%, 21/40) and D8S1771 (52.5%, 21/40). LOH on D8S277 was significantly higher in cases with positive serum HBsAg than in those with negative HBsAg (P < 0.01). Similarly, LOH on D8S261, D8S298 and D8S1733 occurred more frequently in patients with negative HBsAg than those with positive HBsAg (P < 0.01). LOH on D8S298 and D8S1771 were more frequent in tumors larger than 3 cm in size (P < 0.05 and P < 0.01 respectively). LOH frequencies of D8S1721 were significantly higher in cases with absent or partially encapsulated tumor than in those with intact tumor capsule (P < 0.05). LOH on D8S298 and D8S1771 were more frequently detected in tumors with intrahepatic metastasis than those without (P < 0.01). MSI was found in 12.5% (7/56) cases. AI was found in 19.6% (11/56) of all cases examined.</p><p><b>CONCLUSIONS</b>Microsatellite alterations on chromosome 8 were frequent in HCC. LOH, possibly representing alterations of the tumor suppressor pathway, may play an important role in hepatocarcinogenesis. MSI, reflecting a dysfunction of the mismatch repair pathway, may also contribute to this process, but in a less significant way. LOH at some particular loci is associated with certain clinicopathological parameters of human HCC.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Allelic Imbalance , Carcinoma, Hepatocellular , Genetics , Pathology , Chromosomes, Human, Pair 8 , Liver , Pathology , Liver Neoplasms , Genetics , Pathology , Loss of Heterozygosity , Microsatellite RepeatsABSTRACT
To study the immunopathological characteristics and differential diagnosis of hepatic angiomyolipoma(AML).Methods:Thirty-six surgically resected hepatic AML were investigated clinicopathologically and immunohistochemically with 10 antibodies.Results:Hepatic AML occurred in 21 females and 15 males,with the mean age of 41.6 years(26-60 years old).The patients with AML often had no special symptoms even had large space-occupying lesions in the liver.The diameter of AML was 2.5 cm to 14 cm(mean 6.8 cm).Histologically,AML was composed of varying heterogeneous mixture of 3 tissue components:blood vessels,smooth muscle and adipose cells.Extramedullary hemopoiesis sometimes existed.According to tissue components,AML was subcategorized into mixed type(19.4%,n=7),lipomatous type(11.1%,n=4),myomatous type(66.7%,n=24),and angiomatous type(2.8%,n=1).The epithelioid smooth muscle cells were sensitive to HMB-45(100%),SMA(100%),and CD117(66.7%) staining.Conclusion:Hepatic AML often contains smooth muscle elements,which have varied morphological features and should be carefully differentiated from hepatocellular carcinoma,mesenchymal hamartoma,and tumors with rich fat or blood vessels.Immunohistochemical staining with HMB-45 and SMA are the best available markers for the diagnosis of hepatic AML.
ABSTRACT
To study the immunopathological characteristics and differential diagnosis of hepatic angiomyolipoma(AML).Methods:Thirty-six surgically resected hepatic AML were investigated clinicopathologically and immunohistochemically with 10 antibodies.Results:Hepatic AML occurred in 21 females and 15 males,with the mean age of 41.6 years(26-60 years old).The patients with AML often had no special symptoms even had large space-occupying lesions in the liver.The diameter of AML was 2.5 cm to 14 cm(mean 6.8 cm).Histologically,AML was composed of varying heterogeneous mixture of 3 tissue components:blood vessels,smooth muscle and adipose cells.Extramedullary hemopoiesis sometimes existed.According to tissue components,AML was subcategorized into mixed type(19.4%,n=7),lipomatous type(11.1%,n=4),myomatous type(66.7%,n=24),and angiomatous type(2.8%,n=1).The epithelioid smooth muscle cells were sensitive to HMB-45(100%),SMA(100%),and CD117(66.7%) staining.Conclusion:Hepatic AML often contains smooth muscle elements,which have varied morphological features and should be carefully differentiated from hepatocellular carcinoma,mesenchymal hamartoma,and tumors with rich fat or blood vessels.Immunohistochemical staining with HMB-45 and SMA are the best available markers for the diagnosis of hepatic AML.
ABSTRACT
Hepatic ischemia-reperfusion injury(IRI)is a critical problem of liver surgery,especially when comes to liver transplantation.Presently.there are no effective measures for diagnosis,prevention and therapy of IRI,as the mechanisms of IRI still remain unclear.This review summarizes several new hepatic ischemia-reperfusion markers related to cell signal transduetion pathway.including transcription factor STAT,HIF-1 and PPARs,transmission factor MAPK,membrane receptor TLR4 and PARs.and iNOS.Animal studies have indicated that IRI was ameliorated by activating or blockading these markers,which might serve as targets for diagnosis,prevention and therapy of IRI.