Micro-RNA-21 and micro-RNA-155 as predictors of a malignant phenotype in melanocytic lesions.

9001 Background: Indeterminate melanocytic lesions represent a therapeutic dilemma and improved diagnostic markers are needed. Expression of microRNAs (miRs) is altered in many tumors, however miR expression has not been carefully explored in melanoma. We hypothesized that miR expression in indeterminate melanocytic lesions could serve as a marker of malignant potential.,The miR expression profile of melanocytic lesions including dermal nevi (n=8), malignant melanoma (n=28), and pathologically indeterminate melanocytic tissues (n=51) was evaluated by Real Time PCR in paraffin-embedded samples, and validated by in situ RT-PCR. The small RNA, RNU6B was an internal control. ANOVA and pairwise comparisons (two-sided α=0.05) were used for analyses.,Significantly higher miR21 expression was observed in malignant melanoma samples as compared to benign nevi (fold increase = 7.6-fold ± 6.7, p<0.0001). miR155 expression was also significantly higher in melanoma samples versus benign nevi (fold increase = 13.3±16.9, p<0.0001). In contrast, other miRs predicted to be upregulated in melanoma by microarray (of 281 analyzed), including miR30d, miR103, miR146b, were not significantly higher in melanoma versus nevi. Indeterminate lesions with >1 mitosis per 10x high power field had significantly higher miR21 and miR155 compared to lesions with no mitotic activity (p=0.0005 and 0.04, respectively). Also, melanocytic lesions with a depth >1 mm had significantly higher levels of miR155 as compared to lesions with a depth <1 mm (p=0.01). miR21 was also elevated in n=13 human melanoma cell lines as compared to nevi. Sentinel lymph node (SLN) biopsies from patients (n=13) diagnosed with indeterminate lesions of the extremity or trunk were examined for expression of miR21 and miR155. Primary lesions associated with a positive SLN biopsy had higher miR21 and miR155 (fold change vs. nevi = 5.1±3.3 and 7.5±9.7, respectively) as compared to lesions associated with a negative biopsy (fold change vs. nevi = 1.3±0.9 and 2.8±3.2, respectively).,miR21 and miR155 are significantly elevated in primary melanomas and indeterminate lesions that possess an aggressive histologic phenotype. Evaluation of miRs may be a useful diagnostic tool in the setting of melanoma. No significant financial relationships to disclose.