RESUMEN
AIM: To show additional prognostic information about the mutational profile and new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification of adenocarcinoma (ADC) in patients without epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatments. METHODS: In human lung ADC patients (n = 125), including 24 lepidic, 67 acinar, 23 papillary, and 11 solid predominant subtypes, EGFR and KRAS were sequenced, and anaplastic lymphoma kinase (ALK) rearrangements were screened using fluorescence in situ hybridization (FISH). RESULTS: EGFR was mutated in 21.6% of patients with 19.57% showing a mean expression. The most frequent EGFR mutation was a deletion in exon 19, followed by an L858R amino acid substitution in exon 21. KRAS was mutated in 26.4% of patients with 50% displaying mean expression. ALK rearrangement was detected in 6 patients (4.8%). Predominant acinar ADC was strongly associated with EGFR and KRAS mutation. Clinical stage, lymph node metastases, and EGFR mutation in exon 18 showed a significant difference in disease-free and overall survival, but only a trend significance for EGFR and KRAS mutations. Multivariate analysis revealed that men aged >71 years, with a history of smoking (<72 packs/year), clinical stage I/II, and acinar histologic subtype presented better survival than women aged ≤ 71 years, with a history of smoking (>72 packs/year), and having a predominant solid ADC and EGFR mutation in exon 18. CONCLUSIONS: These results indicate that the mutational profile and new IASLC/ATS/ERS classification provide additional prognostic information about lung ADC.
Asunto(s)
Adenocarcinoma/clasificación , Adenocarcinoma/genética , Receptores ErbB/genética , Reordenamiento Génico , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/genética , Mutación , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/genética , Transcriptoma , Proteínas ras/genética , Adenocarcinoma/etiología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Adenocarcinoma Papilar/genética , Anciano , Anciano de 80 o más Años , Sustitución de Aminoácidos , Quinasa de Linfoma Anaplásico , Brasil , Carcinoma de Células Acinares/genética , Supervivencia sin Enfermedad , Femenino , Eliminación de Gen , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Tasa de Mutación , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Proteínas Proto-Oncogénicas p21(ras) , Factores de Riesgo , Fumar/efectos adversos , Análisis de SupervivenciaRESUMEN
BACKGROUND: The transcription factor FOXP3 is increased in acute renal rejection, but its influence on graft outcomes is unclear. This study correlated FOXP3 with dendritic cells and graft outcomes. METHODS: We assessed 96 kidney transplants undergoing allograft biopsy for cause. FOXP3 mRNA was analyzed by real-time polymerase chain reaction (PCR) and FOXP3 protein and DCsCD83(+) by immunohistochemistry. Graft function and survival were assessed at 5 years post-transplantation, as well as by independent predictors of graft loss. RESULTS: Intragraft FOXP3 gene and protein expression were significantly correlated (r = 0.541, p < 0.001). Both FOXP3 mRNA and protein were increased in patients with acute rejection (AR). High expression of FOXP3 mRNA or protein in biopsies did not correlate with clinical variables, but there was a trend to higher positive variation in the glomerular filtration rate (GFR) from biopsy to last follow-up. Patients with FOXP3-mRNA(high) had more DCsCD83(+) in biopsy, but these cells did not associate with AR. Five-year graft survival was not influenced by either FOXP3 mRNA or protein expressions. CONCLUSIONS: FOXP3 mRNA and protein had a good correlation in archival renal graft tissue. Increased FOXP3 expression was found in AR and FOXP3 associated with high numbers of DCs. However, both FOXP3 mRNA and protein was not associated with better allograft outcomes.
Asunto(s)
Células Dendríticas/metabolismo , Factores de Transcripción Forkhead/metabolismo , Rechazo de Injerto/genética , Supervivencia de Injerto/genética , Trasplante de Riñón , Riñón/metabolismo , ARN Mensajero/metabolismo , Adulto , Biopsia , Brasil , Estudios Transversales , Femenino , Factores de Transcripción Forkhead/genética , Expresión Génica , Tasa de Filtración Glomerular , Rechazo de Injerto/metabolismo , Humanos , Inmunohistoquímica , Riñón/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Análisis de Supervivencia , Trasplante Homólogo , Resultado del TratamientoRESUMEN
This article discusses the importance of biobanking to health research advancement in developing countries by analyzing the impact of the establishment of a tumor bank at the A C Camargo Hospital, a cancer care and research center located in Sao Paulo, Brazil. For the past 13 years, the human biological samples provided by the tumor bank have been used by investigators to study various types of cancer. We analyze the impact of biobanking in the overall quality of research projects performed at our institution. We also summarize the main findings of these investigations focusing on breast, prostate, head-neck, and gastroesophageal tumors, as well as the lessons learned over these years. We conclude that biobanking should be part of the strategy employed by scientists and research institutions dedicated to the study of human diseases.