Analysis of protein tyrosine kinases expression in the melanoma metastases of patients treated with Imatinib Mesylate (STI571, Gleevec)

Journal of Cutaneous Pathology
Doina IvanVictor G Prieto

Abstract

Protein tyrosine kinase (PTK) inhibition has been identified as a promising strategy in the development of new selective therapies, targeting the signaling pathways in melanoma progression. Gleevec, a novel class of anti-tumor drugs, may have a potential therapeutic benefit in melanoma, which involves abnormal activation of abl, c-kit, and platelet-derived growth factor (PDGF) tyrosine kinases. Tumor biopsies from 13 patients with metastatic melanoma were screened by immunohistochemistry for PTK [c-kit, C-abl, Abl-related gene (ARG), PDGF receptor-alpha (PDGFR-alpha) and PDGFR-beta] expression before and after being treated with Gleevec @ 400 mg bid for 2 weeks. Both, percentage of positive cells and staining intensity were evaluated. We found a statistically significant (p < 0.01) selective loss of PTK expression in the follow-up biopsy, both in intensity and number of positive cells. PDGFR-alpha and -beta had the highest level of expression reduction. One patient had a durable clinical response, and the follow-up biopsy showed negative expression for four of the PTKs, namely c-abl, ARG, PDGFR-alpha, and beta. Our study reports for the first time the in vivo effect of Gleevec in the induction of apparently selective reduction ...Continue Reading

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Citations

Jun 28, 2012·Head and Neck Pathology·Hong Gang LiuBeverly Y Wang
Sep 1, 2009·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Carlos A Torres-CabalaDoina Ivan
Mar 26, 2009·Journal of the National Cancer Institute·Bonnie E Gould RothbergDavid L Rimm
Jul 16, 2008·Melanoma Research·Cindy S HwangKevin B Kim
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Jun 9, 2009·The Journal of Dermatology·Yasutoshi HidaSeiji Arase
Jan 6, 2011·Archives of Pathology & Laboratory Medicine·Anne Igbokwe, Dolores H Lopez-Terrada

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