Our work in skin cancer is focused on cutaneous lymphomas and malignant melanoma. The cutaneous low grade B-cell lymphomas, follicular lymphoma and marginal zone B-cell lymphoma (MALT lymphoma), may be difficult to distinguish from benign reactive infiltrates (cutaneous lymphoid hyperplasia). Using immunohistochemistry, in situ hybridization and PCR techniques, these tumors are being characterized and the current classification schemes revised accordingly.
Our work in melanoma concerns molecular phenotypes of the primary and metastatic tumors that may predict prognosis and response to therapy. In collaboration with investigators at Millennium Pharmaceuticals, Inc., we identified a novel melanocyte specific gene, melastatin (TRPM1/MLSN-1), which appears to be a melanoma prognostic factor. Multivariate analysis reveals Melastatin mRNA expression as predictor of melanoma metastasis that is independent from the current gold standard, tumor thickness. MLSN-1 expression is one of the genes studied in the CALGB 500105 clinical trial and the Harvard Skin SPORE projects. The results of sentinel lymph node sampling also factor into melanoma patient prognosis. In the examination of over 2700 tissue sections from patients with cutaneous melanoma we found that immunohistochemical techniques and deeper sectioning leads to the detection of melanoma in 12% of cases diagnosed as negative using routine techniques. The methods used in this study have been adopted by the MGH Department of Pathology for the analysis of sentinel lymph nodes in patients with melanoma. CALGB 500105 will study the correlation of MLSN-1 mRNA expression with sentinel node status in patients with primary cutaneous melanoma.