RESUMO
BACKGROUND: High-grade neuroendocrine tumours (HGNTs) of the lung manifest a wide spectrum of clinical behaviour, but no method for predicting their outcome has been established. MATERIALS AND METHODS: We newly established a monoclonal antibody specifically recognizing the product of the alternatively spliced ACTN4 transcript (namely, variant actinin-4), and used it to examine the expression of variant actinin-4 immunohistochemically in a total of 609 surgical specimens of various histological subtypes of lung cancer. RESULTS: Variant actinin-4 was expressed in 55% (96/176) of HGNTs, but in only 0.8% (3/378) of non-neuroendocrine (NE) lung cancers. The expression of variant actinin-4 was significantly associated with poorer overall survival in HGNT patients (P=0.00021, log-rank test). Multivariate analysis using the Cox proportional hazards model showed that the expression of variant actinin-4 was the most significant independent negative predictor of survival in HGNT patients (hazard ratio (HR), 2.15; P=0.00113) after the presence of lymph node metastasis (HR, 2.25; P=0.00023). CONCLUSIONS: The expression of variant actinin-4 is an independent prognostic factor for patients with HGNTs. This protein has a high affinity for filamentous actin polymers and likely promotes aggressive behaviour of cancer cells. The present clinical findings clearly support this notion.
Assuntos
Actinina/genética , Processamento Alternativo , Neoplasias Pulmonares/genética , Tumores Neuroendócrinos/genética , Idoso , Animais , Western Blotting , Linhagem Celular Tumoral , Feminino , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Over 90% of Ewing's sarcoma/primitive neuroectodermal tumour (ES/PNET) cases have the t(11;22) chromosomal rearrangement, which is also found in other small round cell tumours, including desmoplastic small round cell tumour (DSRCT) and clear cell sarcoma (CCS). Although this rearrangement can be analysed by fluorescence in situ hybridisation (FISH) using routinely formalin fixed, paraffin wax embedded (FFPE) tissues when fresh or frozen tissues are not available, a sensitive and convenient detection method is needed for routine clinical diagnosis. AIMS: To investigate the usefulness of newly developed probes for detecting EWS rearrangement resulting from chromosomal translocations using FISH and FFPE tissue in the clinical diagnosis of ES/PNET, DSRCT, and CCS. METHODS: Sixteen ES/PNETs, six DSRCTs, and six CCSs were studied. Three poorly differentiated synovial sarcomas, three alveolar rhabdomyosarcomas, and three neuroblastomas served as negative controls. Interphase FISH analysis was performed on FFPE tissue sections with a commercially available EWSR1 (22q12) dual colour, breakapart rearrangement probe. RESULTS: One fused signal and one split signal of orange and green, demonstrating rearrangement of the EWS gene, was detected in 14 of 16 ES/PNETs, all six DRSCTs, and five of six CCSs, but not in the negative controls. CONCLUSIONS: Interphase FISH using this newly developed probe is sensitive and specific for detecting the EWS gene on FFPE tissues and is of value in the routine clinical diagnosis of ES/PNET, DSRCT, and CCS.
Assuntos
Neoplasias Ósseas/diagnóstico , Proteínas de Ligação a Calmodulina/genética , Tumores Neuroectodérmicos Primitivos Periféricos/diagnóstico , Proteínas de Ligação a RNA/genética , Sarcoma de Ewing/diagnóstico , Adolescente , Adulto , Idoso , Neoplasias Ósseas/genética , Criança , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 22/genética , Sondas de DNA , Feminino , Formaldeído , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Tumores Neuroectodérmicos Primitivos Periféricos/genética , Inclusão em Parafina , Proteína EWS de Ligação a RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sarcoma de Células Claras/diagnóstico , Sarcoma de Células Claras/genética , Sarcoma de Ewing/genética , Translocação GenéticaRESUMO
BACKGROUND: A small number of malignant peripheral nerve sheath tumours (MPNSTs) are low grade, and the nature of these low grade tumours has never been systematically assessed. AIMS: To describe the clinicopathological, immunohistochemical, and ultrastructural features of low grade MPNST and to discuss the main differential diagnoses. METHODS: Four cases of low grade MPNST were studied, including one coexistent with neurofibromatosis type 1. The tumours were analysed with respect to nuclear atypia, cellularity, nuclear enlargement, hyperchromasia, mitotic rate, and necrosis. Immunohistochemistry was performed by standard techniques, and an ultrastructural study was performed on one tumour. RESULTS: The ages of the patients ranged from 32 to 72 years (mean, 58). Two were male and two were female. Three tumours occurred in the deep tissue, including one in the retroperitoneum, and one was located in the dermal and subcutaneous tissue. The maximum diameters of the tumours ranged from 3.5 to 8.0 cm. Microscopically, all tumours showed moderate hypercellularity, an increased nuclear to cytoplasmic ratio, and hyperchromasia, but exhibited varied growth patterns, including those that were atypical neurofibroma-like, low grade fibromyxoid sarcoma-like, low grade epithelioid, and haemangiopericytoma-like. All tumours showed immunoreactivity for S-100 protein and vimentin. CONCLUSIONS: These findings suggest that careful clinical and histological evaluation, along with S-100 protein immunostaining, are essential for the accurate diagnosis of low grade MPNST.