DF/HCC Program Affiliation

Cutaneous Oncology and Melanoma

Research Abstract

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.

Publications

• Rothberg BE, Moeder CB, Kluger H, Halaban R, Elder DE, Murphy GF, Lazar A, Prieto V, Duncan LM, Rimm DL.Nuclear to non-nuclear Pmel17/gp100 expression (HMB45 staining) as a discriminator between benign and malignant melanocytic lesions.Mod Pathol 2008 Jun
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• Kim M, Gans JD, Nogueira C, Wang A, Paik JH, Feng B, Brennan C, Hahn WC, Cordon-Cardo C, Wagner SN, Flotte TJ, Duncan LM, Granter SR, Chin L.Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene.Cell 2006 Jun 30;125(7):1269-81.
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• Koehler JE, Duncan LM.Case records of the Massachusetts General Hospital. Case 30-2005. A 56-year-old man with fever and axillary lymphadenopathy.N Engl J Med 2005 Sep 29;353(13):1387-94.
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• Tannous ZS, Mihm MC, Sober AJ, Duncan LM.Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management.J Am Acad Dermatol 2005 Feb;52(2):197-203.
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• Willemze R, Jaffe ES, Burg G, Cerroni L, Berti E, Swerdlow SH, Ralfkiaer E, Chimenti S, Diaz-Perez JL, Duncan LM, Grange F, Harris NL, Kempf W, Kerl H, Kurrer M, Knobler R, Pimpinelli N, Sander C, Santucci M, Sterry W, Vermeer MH, Wechsler J, Whittaker S,
  15692063
• Zubovits J, Buzney E, Yu L, Duncan LM.HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma.Hum Pathol 2004 Feb;35(2):217-23.
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• Ahmed AR, Avram MM, Duncan LM.Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 23-2003. A 79-year-old woman with gastric lymphoma and erosive mucosal and cutaneous lesions.N Engl J Med 2003 Jul 24;349(4):382-9
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• de Leval L, Harris NL, Longtine J, Ferry JA, Duncan LM.Cutaneous b-cell lymphomas of follicular and marginal zone types: use of Bcl-6, CD10, Bcl-2, and CD21 in differential diagnosis and classification.Am J Surg Pathol 2001 Jun;25(6):732-41.
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• Duncan LM, Deeds J, Cronin FE, Donovan M, Sober AJ, Kauffman M, McCarthy JJ.Melastatin expression and prognosis in cutaneous malignant melanoma.J Clin Oncol 2001 Jan 15;19(2):568-76.
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• Deeds J, Cronin F, Duncan LM.Patterns of melastatin mRNA expression in melanocytic tumors.Hum Pathol 2000 Nov;31(11):1346-56.
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• Yu LL, Flotte TJ, Tanabe KK, Gadd MA, Cosimi AB, Sober AJ, Mihm MC, Duncan LM.Detection of microscopic melanoma metastases in sentinel lymph nodes.Cancer 1999 Aug 15;86(4):617-27.
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• Duncan LM.Prognostic Indicators in Melanoma.Harrison's Principles of Internal Medicine. 1999;15:489-518.
• Duncan LM, Deeds J, Hunter J, Shao J, Holmgren LM, Woolf EA, Tepper RI, Shyjan AW.Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis.Cancer Res 1998 Apr 1;58(7):1515-20.
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