Expression of HSP90 in gastrointestinal stromal tumours and mesenchymal tumours.
OBJECTIVE
Heat shock proteins (HSP) are up-regulated under conditions of increased stress, including cancer. Recently, HSP90 has been shown to be crucial to the expression and activation of the KIT oncoprotein. The aim was to explore the role of HSP90 expression as a prognostic marker and therapeutic target in gastrointestinal stromal tumours (GISTs) and other mesenchymal tumours.


RESULTS
The expression of HSP90 was evaluated by immunohistochemistry in 92 GISTs, 47 mesenteric fibromatoses, six schwannomas, leiomyomas, melanomas, malignant peripheral nerve sheath tumours and leiomyosarcomas. Western blotting was performed in 22 selected cases. HSP90 overexpression was found in 33.7% of GISTs and was correlated with non-gastric location, mixed histological subtype, high mitotic index, high risk grades, and specific mutation genotypes. In mesenchymal tumours, HSP90 overexpression was found in 66.7% of malignant peripheral nerve sheath tumours, 83.3% of leiomyosarcomas, and 100% of melanomas. HSP90 expression by Western blotting correlated with the results of immunohistochemistry. The Cox proportional hazards model showed that HSP90 expression is an independent predictor of recurrence in GISTs (P = 0.003).


CONCLUSIONS
Overexpression of HSP90 is predictive of adverse behaviour in GISTs and may provide a therapeutic solution to the challenge of imatinib-resistant GISTs and other mesenchymal sarcomas.
Kang
Gu Hyun
GH
Department of Pathology, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea.
Lee
Eui Jin
EJ
Jang
Ki Taek
KT
Kim
Kyoung-Mee
KM
Park
Cheol Keun
CK
Lee
Choong-Sik
CS
Kang
Dae Young
DY
Lee
Sug Hyung
SH
Sohn
Tae Sung
TS
Kim
Sung
S
D000368:Aged; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009379:Neoplasms, Muscle Tissue / Q000235:genetics / Q000473:pathology; D018317:Nerve Sheath Neoplasms / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics
D018841:HSP90 Heat-Shock Proteins; D019009:Proto-Oncogene Proteins c-kit