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1.
Histopathology ; 59(1): 81-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21668474

RESUMO

AIMS: This study aimed to evaluate the copy number alteration on 2q24, its association with ACVR1 transcript expression and the prognostic value of these data in head and neck squamous cell carcinomas. METHODS AND RESULTS: Twenty-eight samples of squamous cell carcinoma were evaluated by fluorescence in situ hybridization (FISH) using the probes RP11-546J1 (2q24) and RP11-21P18 (internal control). Significant gains at 2q24 were detected in most cases at frequencies varying from 3 to 35%. ACVR1 gains and amplifications were associated with longer overall survival (P = 0.022). ACVR1 mRNA expression analysis in 78 cases revealed overexpression in 44% (34 of 78) of these tumours, suggesting that gene copy number alterations could be involved in gene overexpression. In laryngeal carcinomas, overexpression of ACVR1 mRNA levels was associated with longer overall survival (P = 0.013). Multivariate analysis revealed that ACVR1 is an independent prognostic marker in laryngeal carcinomas (P = 0.012, hazard ratio = 0.165, 95% confidence interval =0.041-0.668). CONCLUSIONS: These findings suggest that copy number alterations at 2q24 can be involved in ACVR1 overexpression, which is associated with longer overall survival in laryngeal carcinomas. To our knowledge, this is the first report indicating the relevance of ACVR1 expression in head and neck cancers.


Assuntos
Receptores de Ativinas Tipo I/genética , Carcinoma de Células Escamosas/genética , Dosagem de Genes , Neoplasias de Cabeça e Pescoço/genética , Idoso , Sequência de Bases , Carcinoma de Células Escamosas/patologia , Cromossomos Humanos Par 2/genética , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Neoplasias Faríngeas/genética , Neoplasias Faríngeas/patologia , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
2.
BMC Cancer ; 9: 90, 2009 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-19309522

RESUMO

BACKGROUND: HER-2 gene testing has become an integral part of breast cancer patient diagnosis. The most commonly used assay in the clinical setting for evaluating HER-2 status is immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). These procedures permit correlation between HER-2 expression and morphological features. However, FISH signals are labile and fade over time, making post-revision of the tumor difficult. CISH (chromogenic in situ hybridization) is an alternative procedure, with certain advantages, although still limited as a diagnostic tool in breast carcinomas. METHODS: To elucidate the molecular profile of HER-2 status, mRNA and protein expression in 75 invasive breast carcinomas were analyzed by real time quantitative RT-PCR (qRT-PCR) and IHC, respectively. Amplifications were evaluated in 43 of these cases by CISH and in 11 by FISH. RESULTS: The concordance rate between IHC and qRT-PCR results was 78.9%, and 94.6% for qRT-PCR and CISH. Intratumoral heterogeneity of HER-2 status was identified in three cases by CISH. The results of the three procedures were compared and showed a concordance rate of 83.8%; higher discordances were observed in 0 or 1+ immunostaining cases, which showed high-level amplification (15.4%) and HER-2 transcript overexpression (20%). Moreover, 2+ immunostaining cases presented nonamplified status (50%) by CISH and HER-2 downexpression (38.5%) by qRT-PCR. In general, concordance occurred between qRT-PCR and CISH results. A high concordance was observed between CISH/qRT-PCR and FISH. Comparisons with clinicopathological data revealed a significant association between HER-2 downexpression and the involvement of less than four lymph nodes (P = 0.0350). CONCLUSION: Based on these findings, qRT-PCR was more precise and reproducible than IHC. Furthermore, CISH was revealed as an alternative and useful procedure for investigating amplifications involving the HER-2 gene.


Assuntos
Neoplasias da Mama/patologia , Hibridização in Situ Fluorescente/métodos , Receptor ErbB-2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Amplificação de Genes , Dosagem de Genes , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/metabolismo , Reprodutibilidade dos Testes
3.
Genet. mol. biol ; 26(2): 121-128, Jun. 2003. ilus, tab
Artigo em Inglês | LILACS | ID: lil-345960

RESUMO

Head and neck carcinomas represent the sixth most frequent type of cancer in the world, and 90 percent are derived from squamous cells (HNSCC). In this study of 15 HNSCC cases, extensive aneuploidy was detected by G banding in most tumors. The most frequently observed numerical changes involved gain of a chromosome 22, and loss of chromosomes Y, 10, 17, and 19. The most frequent structural alteration was del(22)(q13.1). As compared to G-banding, fluorescence in situ hybridization (FISH) proved to be an effective technique for detecting aneuploidy. Interphase FISH with a chromosome 17 centromere probe disclosed a high frequency of monosomy for chromosome 17, in contrast with G-banding, by which clonal monosomy 17 was detected in only three of the tumors. Painting probes for chromosomes 5 and 16 were used to evaluate a selected series of HNSCC in which G-banding analysis had shown marker chromosomes. FISH analysis failed to confirm the origin of the marker chromosomes, but four out of five cases showed a significant loss of chromosomes 5. This difference between FISH and G-banding results may reflect the smaller number of metaphase analyzed as well as the criteria adopted for sorting these metaphases. Therefore results obtained solely by G-banding analysis should be considered with caution. Our data confirmed the involvement of chromosome 17 in head and neck squamous cell carcinomas


Assuntos
Humanos , Aberrações Cromossômicas , Cromossomos Humanos Par 17 , Neoplasias de Cabeça e Pescoço , Hibridização in Situ Fluorescente , Análise Citogenética
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