MITF Expression in Cutaneous Melanoma and Spitz Nevi: A Genomic and Immunohistochemical Study
JL Baran, K Scott, A Muzikansky, L Chin, LM Duncan. Massachusetts General Hospital/ Harvard Medical School, Boston, MA; Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA
Background: Spitz nevi are spindled and epithelioid cell melanocytic proliferations that may histologically mimic melanoma.
Design: In an effort to further define the genomic profile of these tumors, we used a branched chain DNA assay to measure RNA in formalin fixed tumors from 40 patients. We evaluated twenty-five genes determined to be of interest based on prior work and current collaborations. We then examined the protein expression of the most robust discriminator of Spitz nevus versus melanoma.
Results: Twenty cases of Spitz nevus and 20 cases of vertical growth phase melanoma were evaluated. Of the 20 patients with Spitz nevi, ages ranged from 4 to 65 years (mean 26). All 20 patients were alive without evidence of disease, with a mean follow up of 11 years. Of the 20 patients with melanoma, the patient ages ranged from 20 to 77 years (mean 57). Twelve patients diagnosed with melanoma were without recurrence or metastasis (mean follow up 11 years). Eight patients with metastases died of melanoma, with an average survival time of 3 years. MITF was found to express the most significant difference in RNA levels between Spitz nevus and melanoma (p<0.01), with higher expression in melanomas than Spitz. However, no significant association of MITF with survival was observed while IL24 showed the most robust association with survival (p<0.04). MITF protein expression was also evaluated immunohistochemically and revealed no discernible correlation with RNA levels. MITF was detected immunohistochemically in all 20 Spitz tumors and 17/20 (85%) melanomas. Diffuse MITF expression was observed in 16/20 (80%) Spitz nevi and 8/20 (40%) melanomas. Regional staining for MITF was observed in 2/20 (10%) Spitz nevi and 8/20 (40%) melanomas. Scattered MITF expression was the least frequently observed pattern of MITF, with 2/20 (10%) of Spitz nevi and 1/20 (5%) of melanomas. Among the novel metastasis genes, we also identified 6 exhibiting significant differential expression between Spitz and melanoma. This data will be presented.
Conclusions: In conclusion, in routinely processed tumor specimens, we identified 7 genes with differential RNA expression between Spitz nevi and melanomas including MITF; immunohistochemical detection of MITF was not revealed as a diagnostic or prognostic factor.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 75, Wednesday Afternoon