RESUMO
BACKGROUND: The prospective trial of intraoperative detection of carcinoembryonic antigen mRNA (mCEA) in pleural lavage in patients undergoing resection for nonsmall cell lung cancers (NSCLCs) was undertaken to analyze clinical applicability. METHODS: From January 2006 to August 2008, cytology and mCEA analysis with pleural lavage were performed for 383 patients undergoing resection of NSCLCs. The pleural cavity was washed with 100 mL of physiological saline, and recovered lavage fluid was divided into two portions, one for pleural lavage cytology and the other for determination of mCEA expression by the transcription reverse transcription concerted reaction method. RESULTS: One hundred and nineteen (31%) cases were mCEA-positive. Positive mCEA results were observed frequently for adenocarcinoma patients and were recognized as a suggestive prognostic factor by stepwise regression analyses (p = 0.0472). The overall 4-year survival rate was 56% in the mCEA-positive group and 81% in the negative cases (p = 0.003). Of 71 cases suffering recurrence, it occurred frequently in mCEA-positive group (p = 0.035). CONCLUSION: Intraoperative mCEA analysis may be a reliable indicator for assessing short-term prognosis and likelihood of early recurrence.
Assuntos
Adenocarcinoma/genética , Antígeno Carcinoembrionário/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , RNA Mensageiro/análise , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Distribuição de Qui-Quadrado , Feminino , Humanos , Cuidados Intraoperatórios , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Cavidade Pleural , Pneumonectomia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Irrigação Terapêutica/métodos , Fatores de Tempo , Resultado do TratamentoRESUMO
A positive finding on intraoperative pleural lavage cytology (PLC) is considered a possible prognostic factor in patients non-small cell lung cancers (NSCLCs). Patients negative for cancer cells on PLC, however, have occasionally developed recurrence after surgery. In this study, we evaluated the significance of the rapid intraoperative detection of carcinoembryonic antigen-mRNA(mCEA) in pleural lavage in patients with NSCLCs for detecting subclinical recurrence. In 298 NSCLC patients, PLC and mCEA expression of the cell fraction in pleural lavage fluids was analyzed immediately after thoracotomy. The results of mCEA detection by the transcription reverse transcription concerted (TRC) quantitative method and PLC with reference to clinicopathologic characteristics and recurrence patterns were analyzed. The TRC analysis was completed within 90 minutes. Eighty-seven patients (30.9%) were mCEA-positive, and 8(2.7%) were PLC-positive and all mCEA-positive. The positive mCEA rates were not significantly associated with histology or the serum CEA level. Patients with positive the mCEA results showed higher recurrence rates than the mCEA-negative group (5-11%). Thus, intraoperative mCEA analysis by the TRC method should be considered as a sensitive aid to assessing the microscopic spread of malignant cells into the pleural cavity in association with recurrence.
Assuntos
Biomarcadores Tumorais/análise , Antígeno Carcinoembrionário/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Período Intraoperatório , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Técnicas de Diagnóstico Molecular/métodos , Recidiva Local de Neoplasia , Técnicas de Amplificação de Ácido Nucleico/métodos , Pleura/patologia , RNA Mensageiro/análise , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Citodiagnóstico , Neoplasias Pulmonares/cirurgia , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Irrigação TerapêuticaRESUMO
It has been estimated that genetic factors or a combination of genetic and environmental factors play a role in the development of 10-15% of all cancers. A genetic cause of hereditary cancer has been identified in more than 40 diseases till now. For preventing this cancer, gene testing is essential because it has no definite clinical marker as in hereditary non-polyposis colorectal cancer: HNPCC. Much more experience must be accumulated in this testing at the clinical base in order to increase specificity and sensitivity while safeguarding ethical, legal and social issues (ELSI). Recently, the Personal Information Protection Law was enforced. Gene inspection involving hereditary cancer should be carried out under a comprehensive gene medical examination organization. It is important for the family doctor, medical specialist, and gene inspection person in charge to cooperate closely with one another, and this will be a subject of future study.
Assuntos
Bases de Dados Genéticas , Aconselhamento Genético , Testes Genéticos , Síndromes Neoplásicas Hereditárias , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Teste de Complementação Genética , Humanos , Consentimento Livre e Esclarecido , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/prevenção & controle , Reação em Cadeia da PolimeraseRESUMO
We established 2 novel human cell lines (GCCOT-1, GCCRK) from glassy cell carcinoma. Both cell lines showed dual tendencies of glandular and squamous differentiation, and thus possess the characteristics resembling reserve cells, the putative origin of most carcinomas arising from the uterine cervix. HPV type 18 DNA including E6-E7, which is commonly found in cell types other than squamous cell carcinoma of uterine cervix, was detected in both cell lines. We analyzed gene copy number alterations of the 2 cell lines using conventional comparative genomic hybridization (CGH) coupled with array-based CGH. Among the putative oncogenes demonstrating copy number gain in both cell lines, FGR(SRC2) at 1p36.2-1 and LAMC2 at 1q25-31 have not been reported to show amplification in previous analyses of conventional cervical cell lines. These oncogenes are thus speculated to be directly associated with oncogenesis of glassy cell carcinoma. On the other hand, among the putative suppressor genes demonstrating copy number loss in both cell lines, the 9q region, ATM at 11q22.3, and CYLD at 16q12-13 have not been reported to show loss in conventional cervical cancer cell lines. These sites are speculated to be important as tumor suppressors directly associated with oncogenesis of glassy cell carcinoma. This study suggests for the first time that together with the presence of HPV type 18, alterations at the above sites are closely associated with oncogenesis of glassy cell carcinoma, a special type of carcinoma in the uterine cervix.
Assuntos
Carcinoma Adenoescamoso/virologia , Proteínas de Ligação a DNA , Hibridização de Ácido Nucleico , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/virologia , Neoplasias Uterinas/virologia , Adulto , Proteínas Mutadas de Ataxia Telangiectasia , Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/patologia , Proteínas de Ciclo Celular , Aberrações Cromossômicas , Sondas de DNA de HPV , DNA de Neoplasias/genética , DNA Viral/análise , Enzima Desubiquitinante CYLD , Feminino , Dosagem de Genes , Humanos , Cariotipagem , Laminina/genética , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Oncogênicas Virais/metabolismo , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/genética , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genética , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , Quinases da Família srcRESUMO
HYPOTHESIS: There have been few reports on the minimum surgical margins (SMs) required for successful liver resection in patients with colorectal metastases. This minimum requirement may be narrower than the previously recommended margin of 10 mm. OBJECTIVES: To identify the minimum margins by assessing the presence of micrometastases around the tumor using genetic and histological techniques, and to investigate whether SMs are associated with patterns of tumor recurrence or patient survival. DESIGN: Prospective and retrospective studies. SETTING: Tertiary referral cancer center. PATIENTS AND METHODS: Fifty-eight patients who underwent 62 liver resections for hepatic metastasis from colorectal cancer between December 1, 1996, and November 30, 2000, were included in the study. Tissue samples taken from the tumor, surrounding liver parenchyma, and Glisson pedicle near the tumor were tested for K-ras and p53 mutations using the mutant allele-specific amplification method. For the retrospective study on patient outcomes, 194 patients who had undergone liver resections between 1980 and 2000 were analyzed according to their SMs. RESULTS: Of the 62 sets of samples from liver metastases, 39 were positive for K-ras and p53 gene mutations or both. Micrometastases in the liver parenchyma surrounding colorectal metastases were present in 2.0% (4/199) of tested samples and were located within 4 mm of the tumor border. Micrometastases via Glisson pedicle were more common (14.3% [3/21]), but these were also confined to a short distance from the tumor edge (
