Vascular endothelial growth factor receptor 2 and downstream p38 mitogen-activated protein kinase are possible candidate markers of intrinsic resistance to adjuvant endocrine treatment in steroid receptor positive breast cancer - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Breast Cancer Research and Treatment Année : 2010

Vascular endothelial growth factor receptor 2 and downstream p38 mitogen-activated protein kinase are possible candidate markers of intrinsic resistance to adjuvant endocrine treatment in steroid receptor positive breast cancer

Résumé

A cross talk between tyrosine kinase receptors and mitogen-activated protein kinases (MAPKs) is proposed as involved in endocrine resistance. We wanted to investigate intratumoral levels of vascular endothelial growth factor receptor 2 (VEGFR2) and p38 MAPK in relation to relapse-free (RFS) and breast cancer corrected survival (BCCS) after adjuvant endocrine treatment, mainly tamoxifen for 2 or 5 years. We also wanted to investigate these markers in relation to early and late recurrences. VEGFR2 ( = 381) and p38 ( = 174) were determined by enzyme-linked immuno-sorbent assays in tumor homogenates from primary BC diagnosed 1993-1996. Wide ranges of VEGFR2 and p38 proteins were found; median 0.72 pg/μg DNA (range 0.0-11.66), and 0.04 pg/μg DNA (range 0.0-6.79), respectively. Detectable levels of p38 were registered in 65% and classified positive. Higher VEGFR2 were correlated to higher VEGF ( = 0.005), p38 MAPK ( = 0.018), negative ER ( = 0.008), larger tumors ( = 0.001), histopathological grade III ( = 0.018), distant metastasis ( = 0.044), shorter RFS ( = 0.013), and shorter BCCS ( = 0.017). Expression of p38 was significantly correlated with negative PgR ( = 0.044) and with early relapses ( = 0.021), while no difference was seen during the later follow-up period ( = 0.73). Higher VEGFR2 had a significant negative impact on both early ( = 0.029) and later recurrences ( = 0.018), while VEGF only predicted later relapses ( = 0.037). Our preliminary results suggest higher intratumoral levels of VEGFR2 and p38 MAPK as candidate markers of intrinsic resistance for adjuvant endocrine therapy.
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hal-00595942 , version 1 (26-05-2011)

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Barbro K. Linderholm, Henrik Hellborg, Ulla Johansson, Lambert Skoog, Janne Lehtiö. Vascular endothelial growth factor receptor 2 and downstream p38 mitogen-activated protein kinase are possible candidate markers of intrinsic resistance to adjuvant endocrine treatment in steroid receptor positive breast cancer. Breast Cancer Research and Treatment, 2010, 125 (2), pp.457-465. ⟨10.1007/s10549-010-1252-x⟩. ⟨hal-00595942⟩

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