RESUMEN
Neuroendocrine tumors can develop in various organs. All of these tumors are designated on the basis of their morphologic characteristics evident by light microscopy, and by immunohistochemistry for antigens such as synaptophysin, chromogranin-A, and CD56/NCAM. In the present study, we attempted to demonstrate the localization of Zonula occludens-1 (ZO-1) and N-cadherin in rosette structures of neuroendocrine tumors using immunohistochemistry and to clarify their specific distribution in rosettes in human pulmonary neuroendocrine tumors in comparison with various types of adenocarcinoma. Among 40 neuroendocrine tumors of the lung examined, 18 cases (45%) and 22 cases (55%) were positive for ZO-1 and N-cadherin, respectively. In addition, we divided the cases into two types: 16 cases of Flexner-type tumor and 24 cases of Homer-Wright-type tumor. We then determined the Rosette Index (RoI; the percentage fraction of rosette structures positive for ZO-1 or N-cadherin among the total number of rosette structures). The Flexner-type neuroendocrine tumors showed significantly higher levels of RoI in ZO-1 than the Homer-Wright-type neuroendocrine tumors (median; 38.8% vs 0%, p < 0.001). On the other hand, N-cadherin and ZO-1 were hardly detected in tubular adenocarcinomas in various organs, and their immunoreactivities differed significantly between adenocarcinoma and pulmonary neuroendocrine tumor (ZO-1, mean 0.23% vs 18%, p < 0.0001; N-cadherin, mean 0% vs 33%, p < 0.0001). In conclusion, expression of ZO-1 and N-cadherin may reflect the mechanisms leading to rosette formation in neuroendocrine tumors, which possibly recapitulate neural tube formation in embryogenesis and could represent a specific immunohistochemical marker for neuroendocrine carcinoma of the lung.
Asunto(s)
Biomarcadores de Tumor/análisis , Cadherinas/biosíntesis , Neoplasias Pulmonares/metabolismo , Proteínas de la Membrana/biosíntesis , Tubo Neural/metabolismo , Tumores Neuroendocrinos/metabolismo , Fosfoproteínas/biosíntesis , Desarrollo Embrionario , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/patología , Tumores Neuroendocrinos/patología , Formación de Roseta , Proteína de la Zonula Occludens-1RESUMEN
INTRODUCTION: Large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC) show considerable differences in their histology but share neuroendocrine (NE) characteristics and also genetic and/or expression patterns. METHODS: We used the subtractive expression method to identify differences in gene expression that would allow discrimination between these two types of NE lung carcinoma. RESULTS: Eight cDNA fragments were transcribed at a higher level in LCNEC compared with SCLC, and these corresponded to five mitochondrial genes, two ribosomal genes, and one fetal regulation factor, neuronatin (NNAT). Immunohistochemically, NNAT protein was detected in 43% (6/14) of LCNECs but in only 8% (1/13) of SCLCs (p < 0.05). Positive staining for NNAT was observed in areas that did not show the NE morphology, such as palisading and rosettes. CONCLUSIONS: The present results suggest that NNAT has the potential to be used as a differential maker between LCNEC and SCLC.
Asunto(s)
Carcinoma de Células Grandes/genética , Carcinoma Neuroendocrino/genética , Carcinoma de Células Pequeñas/genética , Perfilación de la Expresión Génica , Neoplasias Pulmonares/genética , Animales , Biomarcadores de Tumor/análisis , Antígeno CD56/análisis , Carcinoma de Células Grandes/diagnóstico , Carcinoma Neuroendocrino/diagnóstico , Carcinoma de Células Pequeñas/diagnóstico , Cromogranina A/análisis , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Proteínas de la Membrana/análisis , Ratones , Ratones SCID , Proteínas del Tejido Nervioso/análisis , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , Sinaptofisina/análisisRESUMEN
We reported a case of renal graft loss in cadaveric renal transplantation. An episode biopsy with renal dysfunction showed plasma cell predominant inflammatory infiltration in the interstitium without a finding of vascular or glomerular rejection, and was diagnosed as plasma cell-rich acute rejection (PCAR). Despite intensive immunosuppressive therapy, the renal histology of repeated biopsies showed persistent plasma cell infiltration and the graft was finally lost. Immunohistological staining and immunoglobulin gene rearrangement studies to estimate the clonality of inflammatory cells revealed that the infiltrating plasma cells were polyclonal in origin. Epstein-Barr virus was not detected by in situ hybridization. From these results, we excluded the possibility of post-transplant lymphoproliferative disorder (PTLD); however, a precise definition and differential diagnosis between PCAR and PTLD has not yet been fully determined. As therapeutic regimens for PCAR and PTLD are different, definite guidelines for diagnosis and treatments of PCAR need to be established.
Asunto(s)
Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Trasplante de Riñón/inmunología , Células Plasmáticas/fisiología , Enfermedad Aguda , Cadáver , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Fibroblasts in tumor tissue are thought to interact with tumor cells directly and/or indirectly and to have important roles in tumor invasion and metastasis. To characterize the phenotype of proliferating fibroblasts in pulmonary adenocarcinoma, we established short-term fibroblast cell lines from both normal bronchus and adenocarcinoma tissues obtained from the same patients and compared the gene expression profiles. Four sets of fibroblast cell lines (eight cell lines in total) were used in the analysis. Total RNA was extracted from each cell line and hybridized with 550 cancer-related RNAs blotted on a cDNA filter array. Five up-regulated genes and 12 down-regulated genes (total of 17 genes) were detected in the fibroblast cell lines from the tumor tissues compared with those from normal bronchus. Using real-time quantitative RT-PCR methods, the expression profile of each gene was examined; five genes, one up-regulated (MLH1) and four down-regulated (Cox1, FGFR4, p120, and Smad3), were confirmed. Furthermore, the protein expression levels of the five genes in the cancerous and normal tissues were examined immunohistochemically, and the up-regulation of MLH1 and the down-regulation of Cox1 in cancerous tissue were confirmed in vivo. These results indicate that the proliferating fibroblasts in pulmonary adenocarcinomas are phenotypically different from fibroblasts in normal bronchus tissues.