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Dermatopathology
Research interests: Cutaneous Oncology
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 have been 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 SPORE projects also include correlating environmental and genetic risk factors with molecular signatures in melanoma and determining molecular signatures of the MITF pathway that predict response to therapy.
We are also investigating optimal methods for detection of microscopic melanoma metastases. Immunohistochemical techniques and deeper sectioning leads to the detection of melanoma in 12 percent of cases diagnosed as negative using routine techniques. The methods used in this study have been adopted by MGH Pathology Service for the analysis of sentinel lymph nodes in patients with melanoma and are currently being optimized. The CALGB 500105 clinical trial investigates the correlation of TRPM1/MLSN-1 mRNA expression with sentinel node status and other prognostic factors in patients with primary cutaneous melanoma. |