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The cytomorphology of MPNST in effusion specimens is rarely described. In this paper, the detailed cytopathological and immunohistochemical characteristics of metastatic MPNST has been described in pleural effusion. Patients' medical history and the judicious utilization of ancillary studies contribute to ensure precise cytological diagnoses. The cytomorphology of malignant peripheral nerve sheath tumour (MPNST) in effusion specimens can be diagnostically challenging. The author presents detailed cytopathological and immunohistochemical characteristics of a case of metastatic MPNST in pleural effusion.
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Segunda Neoplasia Primária , Neurofibrossarcoma , Derrame Pleural Maligno , Derrame Pleural , Humanos , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patologiaRESUMO
Wogonin (5,7-dihydroxy-8-methoxyflavone), a natural flavonoid compound in herbal plants, can suppress growth in hepatocellular carcinoma (HCC). However, the microRNA (miRNA) expression profiles that are influenced by wogonin have not been thoroughly described. To explore the novel miRNAs and the biological mechanism underlying the effect of wogonin on HCC cells. The effect of wogonin on Huh7 cell growth was assessed both in vitro and in vivo. The expression profiles of miRNAs were obtained by small RNA sequencing. Luciferase reporter experiment and bioinformatics analysis were conducted to determine whether tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) can bind to miR-27b-5p. Effects of the ectopic expression of YWHAZ and miR-27b-5p on Huh7 cells proliferation and apoptosis were evaluated. Furthermore, the cell cycle, apoptosis and multiple signaling pathway-related molecules were detected by Western blot analysis. Wogonin substantially inhibited the growth of Huh7 cells both in vitro and in vivo. Seventy miRNAs exhibited greater than twofold changes in wogonin-treated cells. Upregulation of miR-27b-5p inhibited Huh7 cell proliferation, and the anticancer effect of wogonin was reversed after miR-27b-5p knockdown. miR-27b-5p directly targeted YWHAZ in HCC cells. The proliferation-inhibiting effect of miR-27b-5p was revoked by YWHAZ overexpression. Meanwhile, inhibition of HCC growth was achieved by downregulating YWHAZ. Wogonin exerted antitumor activity through multiple signaling molecules, such as focal adhesion kinase, protein kinase B, mammalian target of rapamycin and molecules related to apoptosis and cell cycle by upregulating miR-27b-5p and downregulating YWHAZ. Our findings suggest that miR-27b-5p/YWHAZ axis contributes to the inhibitory effect of wogonin in HCC by targeting related genes and multiple signaling pathways.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismoRESUMO
INTRODUCTION: Pathological consultation on intraoperative frozen sections plays a crucial role in the management of patients undergoing surgical therapy, and is also a key indicator for quality assurance in anatomical pathology. This study aimed to evaluate the diagnostic accuracy and technical quality of frozen sections in detecting hepatobiliary lesions with malignant potential. PATIENTS AND METHODS: A retrospective database review was performed for 1208 cases intraoperative pathology consultation who underwent hepatobiliary lesions resection at our institution from 2016 to 2020. The intraoperative consultation cases during a 5-year period were reviewed and analyzed, including the measurement of the diagnostic accuracy and turnaround time of frozen sections, the reasons for discrepancies, and the rates of discordance and deferral. RESULTS: In this study, we confirmed that the overall accuracy, sensitivity and specificity were 95.3 %, 96.3 % and 96.6 %, respectively, in distinguishing benign from malignant lesions. The rates of deferred and discordant diagnoses were 2.57 % and 2.2 %, respectively. The overall frozen section turnaround time was 22.1 min. The most common cause of deferred and discordant was poor section quality, the lesion of bile duct margin on the frozen section, misinterpretation of difficult and complicated cases, etc. CONCLUSIONS: This study confirms that the intraoperative frozen sections can serve as a rapid, accurate and robust method for the pathological diagnosis of suspected hepatobiliary lesions. However, it should be noted that some poor technical problems, pathological assessment of tumor margin and difficult cases are the most frequently causes of deferred and discordant interpretations.
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Secções Congeladas , Neoplasias , Humanos , Secções Congeladas/métodos , Estudos Retrospectivos , Encaminhamento e Consulta , Sensibilidade e Especificidade , Período IntraoperatórioRESUMO
BACKGROUND & AIMS: To investigate diagnostic and prognostic values of sulfite oxidase (SUOX) in patients with hepatocellular carcinoma (HCC) who underwent curative resection. METHODS: We investigated immunohistochemically the expression dynamics of SUOX, aldo-ketoreductase family 1 member B10 (AKR1B10) and CD34 at different stages of HCC. The differential diagnostic performance of three markers or their combinations in high-grade dysplastic nodules (HGDNs) and well-differentiated small HCC (WD-sHCC) were investigated by logistic regression models and validated in an independent testing set. Overall survival (OS) and time to recurrence (TTR) were evaluated in 300 patients with HCC as the testing cohort, and validated in 198 patients with HCC. RESULTS: SUOX was decreased and AKR1B10 and CD34 were increased with the stepwise progression of hepatocarcinogenesis. For differential diagnosis of WD-sHCC from HGDNs, the sensitivity and specificity of the SUOX+AKR1B10+CD34 combination for WD-sHCC detection were 93.8% and 95.2%, respectively, and overall accuracy was much higher than any of the three individual markers and two marker combinations. In addition, SUOX, but not AKR1B10 and CD34, was an independent prognostic factor for OS and TTR, and showed better correlation with OS and TTR if combined with serum α-fetoprotein (AFP) for both the testing and validation cohorts. CONCLUSIONS: SUOX+AKR1B10+CD34 combination could make a substantial contribution to hepatic immunopathological diagnosis to distinguish WD-sHCC from HGDNs. Meanwhile, SUOX combined with serum AFP may predict postoperative outcome and tumor recurrence risk.
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Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/enzimologia , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Aldeído Redutase/metabolismo , Aldo-Ceto Redutases , Antígenos CD34/metabolismo , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , alfa-Fetoproteínas/metabolismoRESUMO
BACKGROUND: Differential diagnosis of high-grade dysplastic nodules (HGDN) and well-differentiated hepatocellular carcinoma (WDHCC) represents a challenge to experienced hepatic clinicians, radiologists and hepatopathologists. METHODS: The expression profiles of aminoacylase-1 (ACY1), sequestosome-1 (SQSTM1) and glypican-3 (GPC3) in low-grade dysplastic nodules (LGDN), HGDN and WDHCC were assessed by immunohistochemistry. The differential diagnostic performances of these three markers alone and in combination for HGDN and WDHCC were investigated by logistic regression models (HGDN = 21; WDHCC = 32) and validated in an independent test set (HGDN, n = 21; WDHCC n = 24). Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses in an independent set of 500 patients. RESULTS: ACY1, SQSTM1 and GPC3 were differentially expressed in each group. For the differential diagnosis of WDHCC from HGDN, the sensitivity and specificity of the combination of ACY1 + SQSTM1 + GPC3 for detecting WDHCC were 93.8% and 95.2% respectively in the training set, which were higher than any of the three two-marker combinations. The validities of the four diagnostic models were further confirmed in an independent test set, and corresponding good sensitivity and specificity were observed. Interestingly, GPC3 expression in HCC tissues combined with serum α-fetoprotein (AFP) was found to be an independent predictor for overall survival and time to recurrence. CONCLUSIONS: ACY1 + SQSTM1 + GPC3 combination represents a potentially valuable biomarker for distinguishing between WDHCC and HGDN using immunohistochemistry. Meanwhile, low GPC3 staining combined with positive serum AFP may play a practical role in predicting poor postoperative outcome and high tumor recurrence risk.
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Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , Fígado/patologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Amidoidrolases/metabolismo , Carcinoma Hepatocelular/mortalidade , Diagnóstico Diferencial , Glipicanas/metabolismo , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/mortalidade , Gradação de Tumores , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Proteína Sequestossoma-1 , Análise Serial de TecidosRESUMO
BACKGROUND: It is practical significant to seek new applicable adjuvant diagnostic biomarkers to differentiate high-grade dysplastic nodule (HGDN) from well-differentiated minute hepatocellular carcinoma (w-MHCC) due to their closely overlapping morphology. METHODS: In the present study, by using microdissection-based paraffin-embedded tissues, loss of heterozygosity (LOH) patterns of a panel of 22 microsatellite (MS) markers was examined in 8 HGDN, 14 w-MHCC (≤1 cm) and 35 larger HCC (LHCC, >1 cm). RESULTS: The results revealed a stepwise increasing fractional allelic loss from HGDN, w-MHCC and LHCC (0.166±0.141, 0.377±0.198, 0.471±0.264, respectively, P=0.005). Loci-specific analyses showed that LOH on D4S415 (66.7% vs 0.0%, P=0.04), D1S507 (50.0% vs 0.0%, P=0.098), and D9S1752 (50.0% vs 0.0%, P=0.33) occurred more frequently than 50% in w-MHCC, but not in HGDN. On the other hand, LOH on D17S960, D17S1796 and D9S1749 occurred in HGDN, but not in w-MHCC. When compared with w-MHCC, LHCC had a higher LOH frequency on D17S720 (73.9% vs 36.4%, P=0.04), D17S960 (68.8% vs 0.0%, P=0.03) and D17S1796 (81.8% vs 0.0%, P=0.01). CONCLUSIONS: The present study suggests MS-LOH is a simple and specific assay for routinely diagnostic pathology. We recommend that D4S415, D1S507, D9S1752, D17S960, D17S1796 and D9S1749 can be used as the first-line markers for differential diagnosis between HGDN and w-MHCC, and D9S1748, D17S921 and D17S520 with a LOH frequency of 40%-50% in w-MHCC, but netative in HGDN, can be regarded as the second-line candidate markers.
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Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Perda de Heterozigosidade/genética , Repetições de Microssatélites/genética , Adulto , Idoso , Alelos , Diagnóstico Diferencial , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: This study aimed to propose an effective quantitative pathological scoring system and to establish nomogram to assess the stage of cirrhosis and predict postoperative survival of hepatocellular carcinoma (HCC) with cirrhosis patients after hepatectomy. METHODS: The scoring system was based on a retrospective study on 163 patients who underwent partial hepatectomy for HCC with cirrhosis. The clinicopathological and follow-up data of 163 HCC with cirrhosis patients who underwent hepatectomy in our hospital from 2010 to 2014 were retrospectively reviewed. A scoring system was established based on the total value of independent predictive factors of cirrhosis. The results were validated using 97 patients operated on from 2011 to 2015 at the same institution. Nomogram was then formulated using a multivariate Cox proportional hazards model to analyze. RESULTS: The scoring system was ultimately composed of 4 independent predictive factors and was divided into 3 levels. The new cirrhosis system score strongly correlated with Child-Pugh score (r=0.8058, P<0.0001) 3 months after surgery; higher cirrhosis system scores predicted poorer liver function and stronger liver damage 3 months after surgery. Then, a four-factor nomogram for survival prediction was established. The concordance indices were 0.79 for the survival-prediction nomogram. The calibration curves showed good agreement between predictions by the nomogram and actual survival outcomes. CONCLUSION: This new scoring system of cirrhosis can help us predict the liver function and liver injury 3 months after surgery, and the nomogram enabled accurate predictions of risk of overall survival in patients of HCC with cirrhosis after hepatectomy.
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OBJECTIVE: To approach the biopathological features of hilar cholangiocarcinoma and surgical pathological factors which influence the long-term survivals of patients with hilar cholangiocarcinoma. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Seguimentos , Hepatectomia , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
OBJECTIVE: To evaluate the significance of a panel of immunohistochemical markers for distinguishing hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC). METHODS: Ten markers including hepatocyte paraffin 1 (Hep Par 1), polyclonal carcinoembryonic antigen (pCEA), CD34, CD10, CD105, multidrug resistance-associated protein-3 (MRP-3), cyclooxygenase-2 (COX-2), mucinous glycoprotein-1 (MUC-1), aquaporin-1 (AQP-1) and CK19 were immunohistochemically stained in the samples from 90 surgically resected HCC and 80 ICC, respectively,and the positive rate of their expression were compared statistically. RESULTS: The positive expression rates of Hep Par 1, pCEA, CD34, CD10, CD105, MRP-3, COX-2 were 85.6%, 82.2%, 87.8%, 18.9%, 8.9%, 11.1% and 48.9%, respectively, in HCC. While the positive expression rates of MUC-1, AQP-1 and CK19 were 73.8%, 65% and 92.5%, respectively, in ICC. CONCLUSION: Based on our results, Hep Par 1 and CD34 can be used as the first line markers, and pCEA and COX-2 as the second line makers, for differential diagnosis of hepatocellular carcinoma from intrahepatic cholangiocarcinoma. While MUC-1 and CK19 can be used as the first line markers and AQP-1 as the second one for the differential diagnosis of intrahepatic cholangiocarcinoma from hepatocellular carcinoma.
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Neoplasias dos Ductos Biliares/diagnóstico , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/diagnóstico , Colangiocarcinoma/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias dos Ductos Biliares/química , Ductos Biliares Intra-Hepáticos/química , Carcinoma Hepatocelular/química , Colangiocarcinoma/química , Diagnóstico Diferencial , Feminino , Hepatócitos/química , Hepatócitos/patologia , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/química , Masculino , Pessoa de Meia-IdadeRESUMO
Intraductal papillary neoplasm of bile duct (IPNB) is characterized by a spectrum of diseases ranging from low-grade intraepithelial neoplasia to invasive carcinoma. In the present study, we aimed to investigate immunophenotypic features and KRAS mutations in relation to pathological subtypes and grades in Chinese patients with IPNBs. A total of 46 patients with IPNBs and 11 invasive adenocarcinomas arising in IPNBs (invasive IPNBs) were enrolled and clinicopathological data were analyzed. It was found that CK7 was expressed in 42 of the 46 neoplastic lesions. HepPar1 was expressed in 11 of the 46 noninvasive IPNBs, but not in invasive IPNBs. Additionally, CK19 was frequently expressed in both noninvasive IPNBs and invasive IPNBs. The intestinal-type IPNBs had a significantly higher percentage of MUC2 expression relative to the pancreaticobiliary (P=0.015) and gastric-type IPNBs (P<0.001). High-grade IPNBs and invasive IPNBs showed increased expression of cyclin D1, Ki-67, p53, mCEA, and CA19-9. The rate of KRAS mutation was significantly higher in high-grade IPNBs (P=0.001) and invasive IPNBs (P=0.006) than that in low- to intermediate-grade IPNBs. Additionally, KRAS mutation was significantly associated with tumor size, and Ki-67 expression. In conclusion, the expression of cyclin D, Ki-67, p53, mCEA and CA19-9 and KRAS mutation status are significantly correlated with histological grades of IPNBs.
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Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/patologia , Mutação/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Humanos , Imuno-Histoquímica/métodos , Gradação de Tumores , Proteínas Proto-Oncogênicas/genéticaRESUMO
OBJECTIVE: To evaluate the possible association of the MTHFR C677T polymorphism with genetic susceptibility to hepatocellular carcinoma (HCC) in a Chinese population. METHODS: 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. RESULTS: 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. CONCLUSION: The MTHFR C677T polymorphism may be associated with a higher HCC risk in females, but not in males in this population.
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Carcinoma Hepatocelular/genética , Predisposição Genética para Doença , Neoplasias Hepáticas/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-IdadeRESUMO
To clarify the modifying effect of the codon 72 p53 polymorphism on hepatocellular carcinoma (HCC) stratified by chronic hepatitis B virus (HBV) infection status, 111 incident cases of HCC and 424 controls in HBV-negative subjects and 135 cases and 125 controls in HBV-positive subjects were identified. No correlation between the polymorphism and HCC risk was found when comparing the HBV-positive cases to controls. However, in HBV-negative subjects, Arg/Pro and Pro/Pro genotypes had a 1.97-fold and a 3.36-fold increased risk for HCC, respectively. In subjects with the Pro allele and family history of HCC yielded an 11.81-fold increased risk of HCC.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Genes p53 , Hepatite B Crônica/complicações , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Polimorfismo Genético , Adulto , Idoso , Carcinoma Hepatocelular/etiologia , Estudos de Casos e Controles , Códon , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de RiscoRESUMO
AIM: To determine the features of microsatellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC). METHODS: Loss of heterozygosity (LOH) and microsatellite instability (MSI) of 55 microsatellite loci were detected with PCR-based microsatellite polymorphism analyses in tumors and corresponding noncancerous liver tissues of 56 surgically resected HCCs using the MegaBACE 500 automatic DNA analysis system. RESULTS: LOH was found in 44 of 56 HCCs (78.6%) at one or several loci. Frequencies of LOH on 1p, 4q, 8p, 16q, and 17p were 69.6% (39/56), 71.4% (40/56), 66.1% (37/56), 66.1% (37/56), and 64.3% (36/56), respectively. MSI was found in 18 of 56 HCCs (32.1%) at one or several loci. Ten of fifty-six (17.9%) HCCs had MSI-H. Serum HBV infection, alpha-fetoprotein concentration, tumor size, cirrhosis, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with LOH on certain chromosome regions. CONCLUSION: Frequent microsatellite alterations exist in HCC. LOH, which represents a tumor suppressor gene pathway, plays a more important role in hepatocarcinogenesis. MSI, which represents a mismatch repair gene pathway, is a rare event during liver carcinogenesis. Furthermore, LOH on certain chromosome regions may be correlated with clinicopathological characteristics in HCC.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Perda de Heterozigosidade , Repetições de Microssatélites , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: To study the genetic alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC), and to find the tumor related DNA fragments. METHODS: DNA isolated from tumors and corresponding noncancerous liver tissues of 56 HCC patients was amplified by random amplified polymorphic DNA (RAPD) with 10 random 10-mer arbitrary primers. The RAPD bands showing obvious differences in tumor tissue DNA corresponding to that of normal tissue were separated, purified, cloned and sequenced. DNA sequences were analyzed and compared with GenBank data. RESULTS: A total of 56 cases of HCC were demonstrated to have genetic alterations, which were detected by at least one primer. The detestability of genetic alterations ranged from 20% to 70% in each case, and 17.9% to 50% in each primer. Serum HBV infection, tumor size, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with genetic alterations on certain primers. A band with a higher intensity of 480 bp or so amplified fragments in tumor DNA relative to normal DNA could be seen in 27 of 56 tumor samples using primer 4. Sequence analysis of these fragments showed 91% homology with Homo sapiens double homeobox protein DUX10 gene. CONCLUSION: Genetic alterations are a frequent event in HCC, and tumor related DNA fragments have been found in this study, which may be associated with hepatocarcinogenesis. RAPD is an effective method for the identification and analysis of genetic alterations in HCC, and may provide new information for further evaluating the molecular mechanism of hepatocarcinogenesis.
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Carcinoma Hepatocelular/genética , DNA de Neoplasias/genética , Neoplasias Hepáticas/genética , Técnica de Amplificação ao Acaso de DNA Polimórfico/métodos , Adolescente , Adulto , Sequência de Bases , Clonagem Molecular , Primers do DNA , DNA de Neoplasias/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência MolecularRESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Carcinoma Hepatocelular/genética , Predisposição Genética para Doença/genética , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/genética , Povo Asiático/genética , Carcinoma Hepatocelular/etnologia , China , Códon/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Neoplasias Hepáticas/etnologia , Masculino , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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Carcinoma Hepatocelular/genética , Genes Supressores de Tumor , Neoplasias Hepáticas/genética , Perda de Heterozigosidade , Instabilidade de Microssatélites , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Feminino , Genes APC , Genes DCC , Genes MCC , Genes p53 , Humanos , Lactente , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: To investigate the genomic instability and their association with clinicopathological characteristics in hepatocellular carcinoma (HCC). METHODS: DNA isolated from tumors and corresponding non-cancerous liver tissues of 56 patients with HCC was amplified with ten random 10-mer arbitrary primers by the random amplified polymorphic DNA (RAPD) method. RESULTS: All the cases of HCC were demonstrated to have genomic instability by at least one primer. The incidence of genomic instability ranged from 20 to 70% in each case, and 17.9-50% in each primer. Serum AFP concentration, HBV infection, tumor size, histological grade, tumor capsule invasion, as well as intrahepatic metastasis were associated with the genomic instability on certain primers. CONCLUSIONS: Genomic instability is a frequent event in HCC. The RAPD is an effective method for the identification and analysis of genomic instability in HCC, and it may provide new information for further evaluating the molecular mechanism of hepatocarcinogenesis.
Assuntos
Carcinoma Hepatocelular/genética , Instabilidade Genômica , Neoplasias Hepáticas/genética , Adulto , Idoso , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Feminino , Antígenos de Superfície da Hepatite B/análise , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Técnica de Amplificação ao Acaso de DNA Polimórfico , alfa-Fetoproteínas/análiseRESUMO
OBJECTIVE: To study the features of microsatellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Carcinoma Hepatocelular/genética , Cromossomos Humanos Par 8 , Neoplasias Hepáticas/genética , Perda de Heterozigosidade , Repetições de Microssatélites , Adulto , Idoso , Desequilíbrio Alélico , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To study the clinicopathological characteristics, immunohistochemical features and differential diagnosis of hepatic angiomyolipoma (AML). METHODS: The clinicopathological features of hepatic AML were systematically examined in 44 surgically resected tumor specimens, with additional immunohistochemistry study using 10 relevant antibodies. RESULTS: 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%). CONCLUSIONS: 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.
Assuntos
Angiomiolipoma/patologia , Neoplasias Hepáticas/patologia , Fígado/patologia , Adulto , Idoso , Angiomiolipoma/classificação , Angiomiolipoma/imunologia , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/classificação , Neoplasias Hepáticas/imunologia , Masculino , Antígenos Específicos de Melanoma , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Proteínas Proto-Oncogênicas c-kit/análiseRESUMO
OBJECTIVE: To study the features of micro satellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC). METHODS: 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. RESULTS: 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. CONCLUSION: 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.