RESUMO
As a part of an international study on the molecular analysis of Diffuse Large B-cell Lymphoma (DLBCL), a robust protocol for gene expression analysis from RNA extraction to qRT-PCR using Formalin Fixed Paraffin Embedded tissues was developed. Here a study was conducted to define a strategy to validate the previously reported 6-gene (LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2) model as predictor of prognosis in DLBCL. To avoid variation, all samples were tested in a single centre and single platform. This study comprised 8 countries (Brazil, Chile, Hungary, India, Philippines, S. Korea, Thailand and Turkey). Using the Kaplan-Meier and log rank test on patients (n=162) and two mortality risk groups (with those above and below the mean representing high and low risk groups) confirmed that the 6-gene predictor score correlates significantly with overall survival (OS, p<0.01) but not with event free survival (EFS, p=0.18). Adding the International Prognostic Index (IPI) shows that the 6-gene predictor score correlates significantly with high IPI scores for OS (p<0.05), whereas those with low IPI scores show a trend not reaching significance (p=0.08). This study defined an effective and economical qRT-PCR strategy and validated the 6-gene score as a predictor of OS in an international setting.
Assuntos
Biomarcadores Tumorais/genética , Fixadores/química , Formaldeído/química , Perfilação da Expressão Gênica/métodos , Linfoma Difuso de Grandes Células B/genética , Inclusão em Parafina , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fixação de Tecidos/métodos , Transcriptoma , Idoso , Ásia , Biópsia , Intervalo Livre de Doença , Europa (Continente) , Feminino , Perfilação da Expressão Gênica/normas , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real/normas , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , América do Sul , Fatores de TempoRESUMO
UNLABELLED: Bone marrow is an important extranodal site in diffuse large B-cell lymphoma (DLBCL), and marrow histology has been incorporated into the new National Comprehensive Cancer Network international prognostic index. Marrow involvement demonstrated histologically confers poor prognosis but is identified by staging PET in more cases. How information from staging PET and biopsy should be combined to optimize outcome prediction remains unclear. METHODS: The International Atomic Energy Agency sponsored a prospective international cohort study to better define the use of PET in DLBCL. As a planned subsidiary analysis, we examined the interplay of marrow involvement identified by PET and biopsy on clinical outcomes. RESULTS: Eight countries contributed 327 cases with a median follow-up of 35 mo. The 2-y outcomes of cases with no evidence of marrow involvement (n = 231) were 81% (95% confidence interval [CI], 76%-86%) for event-free survival (EFS) and 88% (83%-91%) for overall survival (OS); cases identified only on PET (n = 61), 81% (69%-89%) for EFS and 88% (77%-94%) for OS; cases indentified only on biopsy (n = 10), 80% (41%-95%) for EFS and 100% for OS; or cases identified by both PET and biopsy (n = 25), 45% (25%-64%) for EFS and 55% (32%-73%) for OS. The hazard ratios for PET-negative/biopsy-negative cases versus PET-positive/biopsy-positive cases were 2.67 (95% CI, 1.48-4.79) for EFS and 3.94 (1.93-8.06) for OS. CONCLUSION: This large study demonstrates that positive iliac crest biopsy histology only confers poor prognosis for patients who also have abnormal marrow (18)F-FDG uptake identified on the staging PET scan. Abnormal (18)F-FDG uptake in marrow, when iliac crest biopsy histology is normal, has no adverse effect on outcomes.