RESUMO
The aim of this study was to investigate the expression of bcl-2, p53 oncoproteins, and Ki-67 antigen in a series of transitional cell bladder carcinomas and its relation to the traditional prognostic indicators and patient's survival. One hundred six cases with transitional cell carcinoma (TCC) were examined for detection of bcl-2, p53 proteins, and Ki-67 antigen (MIB1 antibody). Bcl-2 immunohistochemical positivity was observed in 52% of TCCs and in 57% of low-grade and 44% of high-grade TCCs. Bcl-2 was also detected in normal urothelium and dysplastic lesions with basal cell expression, and negative staining was observed in carcinomas in situ. Tumor stage showed a significant inverse correlation with overall bcl-2 positivity. The loss of bcl-2 protein expression in higher-stage TCCs was statistically significant (Pt = .01). p53 protein was overexpressed in 50% of TCCs and more frequently in invasive and in carcinomas in situ than in superficial TCCs (Pt = .03). In contrast, detection of p53 was not observed in normal and dysplastic urothelium. p53 positivity was related to the degree of differentiation and to the stage of the disease (Pf = .01 and Pt = .03, respectively). Concerning Ki-67 antigen, its expression was found in 57.5% of TCCs. There was a strong overall correlation of Ki-67 with tumor stage (Pt = .002) and grade (Pf = .002). Univariate statistical analysis showed that the expression of p53 and Ki-67 was significantly correlated to poor prognosis (P = .02, P = .02, respectively). On multivariate analysis, none of these markers but only stage and grade were significantly correlated to prognosis (P = .02, P = .02, respectively). These findings suggest that overexpression of bcl-2 protein may be an early event in tumorigenesis. Tumors with loss of bcl-2 positivity and overexpression of p53 and Ki-67 had an unfavorable prognosis; however, in multivariate analysis, they had no independent prognostic value.
Assuntos
Carcinoma de Células de Transição/metabolismo , Antígeno Ki-67/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologiaRESUMO
AIMS: The aim of this study is to identify prognostic factors influencing survival in patients with gastrointestinal stromal tumors (GISTs) and to identify a mathematical model that can predict lifetime expectation. METHODS: One hundred and two patients with GISTs, were followed retrospectively for a median period of 32 months (from 1 to 82 months). Complete follow-up data were available in 72 cases. All tumors were surgically resected and examined by conventional light microscopy, immunohistochemistry and image analysis. The tumors' location, size, histologic characteristics, immunophenotype, proliferative activity index (assessed by proliferating cell nuclear antigen (PCNA) and Ki-67 immunoreactivity) and the apoptotic markers bcl-2 and bax, were considered as potential prognostic factors and were correlated with patient survival. RESULTS: Tumor size >8 cm (p<0.03), presence of necrosis (p<0.02), number of mitoses >5/10 HPF (p<0.01), metastasis (p<0.001), and PCNA index >10% (p<0.004) were significant predictors of poor survival. Bcl-2 protein (p<0.0007) was a favorable prognostic indicator. If all tumors were treated as of uncertain malignant potential, the following mathematic model named GISTs Prognostic Index (GPI), could be formed by the linear regression technique: GPI exp=(49.6 months-Status of metastasis x 22.9185-Size in cm x 0.6801+bcl-2 expression% x 0.2569) (r(2)=0.67) (Prob>F=0.0001). CONCLUSIONS: Tumors' size, necrosis, mitoses, metastasis and PCNA index are independent poor prognosticators, while bcl-2 protein is associated with favorable prognosis. An interesting equation for survival in patient with GISTs has been reported.
Assuntos
Neoplasias Gastrointestinais/diagnóstico , Células Estromais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Apoptose , Intervalo Livre de Doença , Feminino , Neoplasias Gastrointestinais/química , Neoplasias Gastrointestinais/patologia , Humanos , Imuno-Histoquímica , Imunofenotipagem , Expectativa de Vida , Masculino , Microscopia , Pessoa de Meia-Idade , Índice Mitótico , Valor Preditivo dos Testes , Prevalência , Prognóstico , Proteínas Proto-Oncogênicas/análise , Proteínas Proto-Oncogênicas c-bcl-2/análise , Estudos Retrospectivos , Análise de Sobrevida , Proteína X Associada a bcl-2RESUMO
Bcl-2 protein blocks apoptosis and is involved in human intrahepatic bile-duct development. Formalin-fixed, paraffin-embedded archival tissue from 42 HBV and HCV hepatitis [20 acute AH, 22 chronic hepatitis (CH)], 12 active cirrhosis (CR) and 20 hepatocellular carcinoma (HCC) was immunostained for bcl-2 protein. In all cases, bcl-2 protein was detected in portal and intralobular lymphocytes but not in hepatocytes or Kupffer cells. Bcl-2 was positive in the cytoplasm of small portal bile ducts of chronic hepatitis, while it was strongly expressed in newly formed bile-ductules of the limiting plate, mainly in CH with marked activity and CR. Bcl-2 was detected in small bile ducts in only one case of acute hepatitis and was not detected in any case of HCC. Bcl-2 seems to be involved in the regulation of growth and apoptosis of cholangiolar cells. Its expression in small bile ducts and in newly-formed ductules especially in CH with marked activity and CR, implies that the embryonic model of intrahepatic bile duct development may be recapitulated in chronic hepatic disease. Moreover, it supports evidence for the existence of the controversial long-lived stem population in the liver. Bcl-2 does not seem to be involved in hepatocarcinogenesis.
Assuntos
Carcinoma Hepatocelular/metabolismo , Hepatite B Crônica/metabolismo , Hepatite C Crônica/metabolismo , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Doença Aguda , Alanina Transaminase/sangue , Apoptose/fisiologia , Aspartato Aminotransferases/sangue , Ductos Biliares/metabolismo , Biópsia , Carcinoma Hepatocelular/patologia , Hepatite B Crônica/patologia , Hepatite C Crônica/patologia , Humanos , Técnicas Imunoenzimáticas , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologiaRESUMO
BACKGROUND: Hepatocellular carcinoma is one of the most common cancers in the world due to its association with chronic hepatitis infections. Amongst the most usual metastasis of hepatocellular carcinoma are the lymph nodes, the lungs and the bones. Soft tissue metastases are extremely rare. CASE PRESENTATION: Herein, we report the case of a 73-years-old male patient who presented with cervical and upper extremities muscle pain along with paresthesias and a palpable mass on the cervical region. CONCLUSION: This unusual clinical manifestation along with the above-described rare presentations of hepatocellular carcinoma must be taken into account, especially among patients with chronic hepatitis infections. Hippokratia 2014; 18 (3): 285-287.