Dr. Duncan received her MD and Anatomic Pathology training at Washington University School of Medicine in St. Louis, MO, and Dermatopathology Training at the Massachusetts General Hospital. She became a member of the Mass General Dermatopathology Unit faculty in 1991. She serves on the Harvard-MIT Health Sciences and Technology Program advisory board and institutional director of the Harvard Medical School Dermatopathology Fellowship Program. With expertise in the diagnosis of skin cancer, Dr. Duncan's research has led to revised classifications of cutaneous B-cell lymphoma and identification of new biomarkers for malignant melanoma. She reported one of the first series of extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue type (MALT) in the skin, and elucidated the diagnostic features that distinguish this tumor from benign lymphoid infiltrates. Her contributions to the melanoma field include the discovery of the melanocyte specific biomarker Melastatin (TRPM1/MLSN), a prognostic factor for early stage melanoma, the development of a collaborative Skin SPORE tissue microarray platform that has been used internationally to evaluate melanoma biomarkers and the development of a more sensitive analytical platform for melanoma detection in sentinel lymph nodes, in place at the Mass General since 1995. Dr. Duncan's current work is focused on the elucidation of prognostic factors including biomarkers and analytical platforms that inform patient care as predictors of patient outcome and response to therapy. Her mission in the clinical realm is toward more efficient and cost-effective laboratory processing integrated with an expert consultative diagnostic service.
Our work in skin cancer focuses 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 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 detection of melanoma in 12% of cases diagnosed as negative using routine techniques. Methods used in this study have been adopted by Massachusetts General Hospital Pathology Service for 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.
Bibliography of Lyn McDivitt Duncan via PubMed
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