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A subset of colorectal carcinomas express c-KIT protein independently of BRAF and/or KRAS activation

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Abstract

c-KIT is a tyrosine kinase receptor found to be overexpressed in several tumours, namely, GISTs, breast, lung, prostate, ovarian and colorectal carcinomas (CRC). We aimed at determining the frequency of c-KIT expression and mutations in a series of 109 CRC cases (73 primary tumours and 36 lymph node metastases) characterised for KRAS and BRAF mutations. We also aimed at analysing the cellular effects of STI571/Gleevec in CRC-derived cell lines displaying c-KIT expression and KRAS or BRAF mutations. By immunohistochemistry, we found c-KIT overexpression in 15% (11/73) of primary tumours and in 14% (5/36) of metastasis; however, cases showing overexpression did not show c-kit mutations in hotspot regions. The majority (64%) of primary tumours with c-KIT overexpression had mutations at KRAS–BRAF genes. The same was true for 60% of the metastases. We treated CRC cell lines with STI571/Gleevec and verified that it inhibits proliferation and induces apoptosis in all cell lines. In conclusion, overexpression of c-KIT is observed in a subset of primary and CRC metastases in the absence of c-kit mutations. STI571/Gleevec increases apoptosis in CRC cell lines independently of its genetic profile, suggesting that STI571/Gleevec is likely to be an alternative drug for the clinical trials of CRC.

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Acknowledgement

This work was supported by the Foundation for Science and Technology (FCT). We are grateful to the FCT for the grant support to Ana Preto (SFRH/BPD/14882/2003) and for funding the project POCTI/SAU-OBS/56921/2004. We thank Novartis Oncology for funding and for providing us the STI571/Gleevec.

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Authors and Affiliations

  1. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr Roberto Frias s/n, 4200-465, Porto, Portugal

    Ana Preto, Cátia Moutinho, Sérgia Velho, Carla Oliveira, Ana Paula Rebocho, Joana Figueiredo, Paula Soares, José Manuel Lopes & Raquel Seruca

  2. Medical Faculty, University of Porto, 4200-465, Porto, Portugal

    Paula Soares, José Manuel Lopes & Raquel Seruca

  3. Department of Pathology, Hospital São João, 4200-465, Porto, Portugal

    José Manuel Lopes

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  1. Ana Preto
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  2. Cátia Moutinho
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  3. Sérgia Velho
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Correspondence to Ana Preto.

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Preto, A., Moutinho, C., Velho, S. et al. A subset of colorectal carcinomas express c-KIT protein independently of BRAF and/or KRAS activation. Virchows Arch 450, 619–626 (2007). https://doi.org/10.1007/s00428-007-0420-9

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  • DOI: https://doi.org/10.1007/s00428-007-0420-9

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