Annals of Oncology Advance Access originally published online on November 23, 2007
Annals of Oncology 2008 19(3):590-594; doi:10.1093/annonc/mdm545
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melanoma |
HSP90 as a marker of progression in melanoma
1 Department of Medicine, Yale University School of Medicine, New Haven
2 Department of Cell Biology, New York University, New York NY; Departments of
3 Pathology and
4 Dermatology, Yale University School of Medicine, New Haven, CT, USA
* Correspondence to: Dr H. M. Kluger, Section of Medical Oncology, Yale Cancer Center, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Tel: +1-203-785-6221; Fax: +1-203-785-3788; E-mail: harriet.kluger{at}yale.edu
Background: HSP90 chaperones molecules critical for cell survival and malignant progression, including mutated B-raf. HSP90-targeting agents are in clinical trials. No large studies have been conducted on expression of HSP90 in melanomas.
Materials and methods: Tissue microarrays containing 414 nevi, 198 primary and 270 metastatic melanomas were assessed using our automated quantitative analysis (AQUA) method of in situ protein measurement; we use S-100 to define pixels as melanocytes (tumor mask) within the array spot, and measure HSP90 expression within the mask using Cy5-conjugated antibodies.
Results: HSP90 expression was higher in melanomas than nevi (P < 0.0001) and higher in metastatic than primary specimens (P < 0.0001). No association was seen between high HSP90 expression and survival in the primary or metastatic patient subsets. In primary melanomas, high HSP90 expression was associated with higher Clark level (P = 0.0167) and increased Breslow depth (P < 0.0001).
Conclusions: HSP90 expression was significantly higher in tumors than nevi and was associated with disease progression, indicating that it might be a valuable drug target in melanoma, as well as a useful diagnostic marker. Prospective studies are needed to confirm the diagnostic role of HSP90, as well as the predictive role of HSP90 expression in patients treated with HSP90 inhibitors.
Key words: chaperones, diagnostic markers, HSP90, progression markers, therapeutic targets
Received for publication September 1, 2007. Revision received October 20, 2007. Accepted for publication October 29, 2007.
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