HSP90 as a marker of progression in melanoma.
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.


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.
Department of Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
M M
MM
McCarthy
E
E
Pick
Y
Y
Kluger
B
B
Gould-Rothberg
R
R
Lazova
R L
RL
Camp
D L
DL
Rimm
H M
HM
Kluger
D000465:Algorithms; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D018450:Disease Progression; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000737:chemistry* / Q000473:pathology / Q000556:secondary; D012878:Skin Neoplasms / Q000737:chemistry* / Q000473:pathology
D014408:Biomarkers, Tumor; D018841:HSP90 Heat-Shock Proteins