Prompt definitive surgical excision is the treatment of choice for DM. Improved knowledge of the clinical behaviour and histological features of DM is important for more effective management of patients with DM.
Purpose
Gene expression studies in melanoma have been few because tumors are small and cryopreservation is rarely possible. The purpose of this study was to evaluate the Illumina DASL Array Human Cancer Panel for gene expression studies in formalin-fixed melanoma primary tumors, and to identify prognostic biomarkers.
Experimental Design
Primary tumors from two studies were sampled using a tissue microarray needle. Study 1: 254 tumors from a melanoma cohort recruited 2000-2006. Study 2: 218 tumors from a case-control study of patients undergoing sentinel node biopsy.
Results
RNA was obtained from 76% of blocks. 1.4% of samples failed analysis (transcripts from less than 250 of the 502 genes on the DASL chip detected). Increasing age of the block and increased melanin in the tumor were associated with reduced number of genes detected. The gene whose expression was most differentially expressed in association with relapse free survival in study 1 was osteopontin (SPP1, p=2.11×10−6) and supportive evidence for this was obtained in study 2 used as a validation set (p=0.006) (unadjusted data). Osteopontin level in study 1 remained a significant predictor of relapse free survival when data were adjusted for age, sex, tumor site and histological predictors of relapse. Genes whose expression correlated most strongly with osteopontin were PBX1, BIRC5 (Survivin) and HLF.
Conclusion
Expression data were obtained from 74% of primary melanomas and provided confirmatory evidence that osteopontin expression is a prognostic biomarker. These results suggest that predictive biomarker studies may be possible using stored blocks from mature clinical trials.
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