8502 Background: Melanoma patients with clinically involved regional lymph nodes (Stage IIIB&C) represent a prognostically heterogeneous population. Current prognostic factors cannot distinguish the 30% of patients who will achieve long term survival from those who will relapse early. We hypothesized that gene expression profiling could identify these different prognostic groups and provide a greater understanding of the genetic mechanisms involved. Methods: Lymph node sections from 29 patients with Stage IIIB & IIIC melanoma and divergent clinical outcome as defined by time to tumor progression (TTP), including 16 poor (TTP<6 months) and 13 good (TTP>28 months) prognosis patients, were subjected to molecular profiling using spotted oligonucleotide arrays containing 30,888 probes as an initial test set. The differentially expressed genes were determined using a Wilcoxon-Mann-Whitney t-test with the false discovery rate controlling method of Benjamini-Hochberg and validated using quantitative real-time RT-PCR. Using logistic regression, a predictive score algorithm was developed based on the 15 genes for which the correlation between the two platforms was the strongest. The score was then applied to two independent validation sets of 10 and 14 patient samples. Results: Supervised analysis using differentially expressed genes was able to distinguish the two prognostic groups in the test set. The score correlated directly with clinical outcome, with higher scores associated with improved TTP. When the score was then applied to two independent sets of Stage III melanoma patient samples, it predicted clinical outcome accurately in 90% of samples. Conclusions: Stage IIIB and IIIC melanoma can be prognostically sub-classified according to the expression of 15 genes. To our knowledge this is the first study focused on Stage III disease using ex vivo patient samples. These results are encouraging and this genetic signature is currently being validated on a larger cohort. This method will allow appropriate stratification of stage III melanoma patients in adjuvant clinical trials, ameliorating the inherent biological heterogeneity that can confound these studies. [Table: see text]
Selective gene-expression profiling of migratory tumor cells in vivo predicts clinical outcome in breast cancer patients
