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. 2008 Mar;19(3):590-4.
doi: 10.1093/annonc/mdm545. Epub 2007 Nov 23.

HSP90 as a marker of progression in melanoma

M M McCarthy  1 , E Pick, Y Kluger, B Gould-Rothberg, R Lazova, R L Camp, D L Rimm, H M Kluger
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Free article

HSP90 as a marker of progression in melanoma

M M McCarthy et al. Ann Oncol. 2008 Mar.
Free article

Abstract

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.

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