RESUMEN
AIMS: Discriminating small-cell lung carcinoma (SCLC) from large-cell neuroendocrine carcinoma (LCNEC) rests on morphological criteria, and reproducibility has been shown to be poor. We aimed to identify immunohistochemical markers to assist this diagnosis. METHODS AND RESULTS: Gene expression profiling on laser captured frozen tumour samples from eight SCLC and eight LCNEC tumours identified a total of 888 differentially expressed genes (DEGs), 23 of which were validated by qRT-PCR. Antibodies to four selected gene products were then evaluated as immunohistochemical markers on a cohort of 173 formalin-fixed paraffin-embedded (FFPE) SCLC/LCNEC tumour samples, including 26 indeterminate tumours without a consensus diagnosis. Three markers, CDX2, VIL1 and BAI3, gave significantly different results in the two tumour types (P < 0.0001): CDX2 and VIL1 in combination (either marker positive) showed sensitivity and specificity of 81% for LCNEC while BAI3 showed 89% sensitivity and 75% specificity for SCLC. Of the 26 indeterminate tumours 15 (58%) showed an immunophenotype suggesting either SCLC or LCNEC, eight (31%) showed staining of both tumour types, and three (11%) were negative for all markers. CONCLUSION: A panel of three markers, BAI3, CDX2 and VIL1, is a useful adjunct in the diagnosis of these tumour types.
Asunto(s)
Carcinoma Neuroendocrino/diagnóstico , Carcinoma Neuroendocrino/metabolismo , Carcinoma de Células Pequeñas/diagnóstico , Carcinoma de Células Pequeñas/metabolismo , Proteínas de Homeodominio/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Proteínas de Microfilamentos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Factor de Transcripción CDX2 , Carcinoma Neuroendocrino/genética , Carcinoma de Células Pequeñas/genética , Estudios de Cohortes , Diagnóstico Diferencial , Perfilación de la Expresión Génica , Proteínas de Homeodominio/genética , Humanos , Inmunohistoquímica , Captura por Microdisección con Láser , Neoplasias Pulmonares/genética , Proteínas de Microfilamentos/genética , Proteínas del Tejido Nervioso/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaAsunto(s)
Actinomicosis/diagnóstico , Tos/microbiología , Enfermedades Pleurales/diagnóstico , Absceso/diagnóstico , Absceso/terapia , Actinomicosis/complicaciones , Actinomicosis/terapia , Anciano , Enfermedad Crónica , Femenino , Humanos , Enfermedades Pleurales/complicaciones , Enfermedades Pleurales/terapia , Fístula del Sistema Respiratorio/microbiología , Pared Torácica , Toracotomía , Tomografía Computarizada por Rayos XRESUMEN
Human parvovirus B19 infection causes several clinical syndromes. Systemic complications due to this illness are rare. Parvovirus B19 associated renal disease is being increasingly recognized. We report two cases with characteristic presentation with a nephrotic syndrome due to parvovirus B19. We discuss the importance of identifying this infection as a cause of endocapillary glomerulonephritis.
Asunto(s)
Glomerulonefritis/virología , Síndrome Nefrótico/etiología , Infecciones por Parvoviridae/complicaciones , Parvovirus B19 Humano , Adulto , Capilares , Femenino , Humanos , Persona de Mediana EdadRESUMEN
We report a case of long-standing, keratinising, squamous metaplasia of the bladder with undiagnosed malignant transformation to squamous cell carcinoma presenting as acute peritonitis secondary to spontaneous perforation of the bladder tumour. This presentation as an acute abdomen mimicking a perforated peptic or duodenal ulcer is the most unusual aspect of the case.
Asunto(s)
Carcinoma de Células Escamosas/complicaciones , Peritonitis/etiología , Neumoperitoneo/etiología , Neoplasias de la Vejiga Urinaria/complicaciones , Abdomen Agudo/etiología , Anciano , Transformación Celular Neoplásica , Diagnóstico Diferencial , Diafragma , Humanos , Masculino , Úlcera Péptica Hemorrágica/diagnósticoRESUMEN
We report an unusual case of prostatic carcinoma in a middle-aged man with symptomatic multifocal intracerebral metastases as its initial manifestation to highlight the importance of its accurate diagnosis and implications on its management and review relevant literature.
Asunto(s)
Adenocarcinoma/secundario , Neoplasias Encefálicas/secundario , Neoplasias de la Próstata/patología , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Biopsia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Terapia Combinada , Craneotomía , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is the most potent growth factor of tumor neovasculature, has been shown to be up-regulated in every tumor studied thus far, and is correlated with tumor stage and progression. To determine whether specific VEGF splice variants were differentially expressed in renal cell carcinomas, 18 polar tumor samples were analyzed by reverse transcription-PCR using primers designed to differentiate between VEGF splice variants. Control tissue was derived from the opposite normal pole. An amplicon of length consistent with the previously described variant VEGF(148) was found in normal kidney tissue. Subsequent sequencing revealed a new VEGF isoform formed by differential splicing from the end of exon 7 into the 3' untranslated region of the mRNA. Cloning of this transcript showed that translation would result in a 165-amino acid peptide with an alternative terminal 6 amino acids, followed by a stop codon. We have termed this new isoform VEGF165b. This isoform was present in 17 of 18 normal kidney samples but only 4 of 18 cases from matched malignant tissue. VEGF165b was therefore expressed in a significantly higher proportion of normal tissue than malignant tissue from the same patients (P < 0.001). To determine the functional significance of this new isoform, we expressed the full-length protein in a heterologous expression system. Conditioned medium containing this isoform significantly and dose dependently inhibited VEGF165-mediated proliferation, migration of endothelial cells, and vasodilatation of mesenteric arteries. This novel isoform VEGF165b is therefore an endogenous inhibitory form of VEGF that is down-regulated in renal tumors and, therefore, may be anti-angiogenesis.