RESUMO
Hepatocyte nuclear factor-4alpha (HNF4alpha) exists in multiple isoforms that are generated by alternative promoter (P1 and P2) usage and splicing. Here we establish monoclonal antibodies (mAbs) for detecting P1 and P2 promoter-driven HNF4alpha, and evaluate their expression in normal adult human tissues and surgically resected carcinomas of different origins. Using immunohistochemical analysis, we demonstrate that, while P1 promoter-driven HNF4alpha is expressed in hepatocytes, small intestine, colon, kidney and epididymis, P2 promoter-driven HNF4alpha is expressed in bile duct, pancreas, stomach, small intestine, colon and epididymis. Altered expression patterns of P1 and P2 promoter-driven HNF4alpha were observed in gastric, hepatocellular and colorectal carcinomas. HNF4alpha was expressed in lung metastases from renal cell, hepatocellular and colorectal carcinoma but was not observed in lung tumours. The P1 and P2 promoter-driven HNF4alpha expression pattern of tumour metastases correlated with the primary site of origin. P1 promoter-driven HNF4alpha was also found in intestinal metaplasia of the stomach. These data provide evidence for the tissue distribution of P1 and P2 promoter-driven HNF4alpha at the protein level and suggest that HNF4alpha may be a novel diagnostic marker for metastases of unknown primary. We propose that the dysregulation of alternative promoter usage of HNF4alpha is associated with the pathogenesis of certain cancers.
Assuntos
Biomarcadores Tumorais/metabolismo , Transformação Celular Neoplásica/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Neoplasias/metabolismo , Regiões Promotoras Genéticas , Animais , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Feminino , Regulação Neoplásica da Expressão Gênica , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/imunologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Masculino , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Proteínas de Neoplasias/metabolismo , Neoplasias/genética , Lesões Pré-Cancerosas/metabolismo , RNA Mensageiro/genética , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Neoplasias Gástricas/metabolismo , Distribuição Tecidual , Células Tumorais CultivadasRESUMO
The aim of this study was to clarify patients', physicians', and nurses' perceptions with regard to the communication of diagnosis to cancer patients in Japan. Sixty-three cancer patients, 35 physicians and 21 nurses were enrolled for this study: 54 of the patients wished to be informed of the diagnosis, of whom 34 had actually been told that they had cancer. Physicians did not tell the truth to the remaining 20 patients, of whom seven were not told the diagnosis because family members objected. Twenty-one of the 35 physicians thought that telling the true diagnosis had a positive effect and 27 thought that disclosure of the diagnosis to cancer patients should be promoted. Sixteen of the 21 nurses did not experience any difficulties with patient care after the diagnosis was disclosed. The present study suggests that medical staff and family members should respect the patient's standpoint because patients have the right to know about their own condition. Physicians should first provide the details of the disease to their patients. Thereafter, family members should be informed, but only with the patient's consent.
