Authors: Vivian Labovsky Leandro Marcelo Martinez María de Luján Calcagno Kevin Mauro Davies Hernán GarcíaRivello Alejandra Wernicke Leonardo Feldman María Belén Giorello Ayelén Matas Francisco Raúl Borzone Scott C Howard Norma Alejandra Chasseing
Publish Date: 2016/07/27
Volume: 37, Issue: 10, Pages: 13377-13384
Abstract
Spindleshaped stromal cells like carcinomaassociated fibroblasts and mesenchymal stem cells influence tumor behavior and can serve as parameters in the clinical diagnosis therapy and prognosis of early breast cancer Therefore the aim of this study is to explore the clinicopathological significance of tumor necrosis factorrelated apoptosisinduced ligand TRAIL receptors Rs 2 and 4 TRAILR2 and R4 and interleukin6 R IL6R in spindleshaped stromal cells not associated with the vasculature as prognostic determinants of early breast cancer patients Receptors are able to trigger the migratory activity among other functions of these stromal cells We conducted immunohistochemical analysis for the expression of these receptors in spindleshaped stromal cells not associated with the vasculature of primary tumors from early invasive breast cancer patients and analyzed their association with clinicopathological characteristics Here we demonstrate that the elevated levels of TRAILR2 TRAILR4 and IL6R in these stromal cells were significantly associated with a higher risk of metastatic occurrence p = 0034 0026 and 0006 respectively Moreover high expression of TRAILR4 was associated with shorter diseasefree survival and metastasisfree survival p = 0013 and 0019 respectively Also high expression of IL6R was associated with shorter diseasefree survival metastasisfree survival and overall survival p = 0003 0001 and 0003 respectively Multivariate analysis showed that IL6R expression was an independent prognostic factor for diseasefree survival and metastasisfree survival p = 0035 This study is the first to demonstrate that high levels of IL6R expression in spindleshaped stromal cells not associated with the vasculature could be used to identify early breast cancer patients with poor outcomesThe authors thank the Pathology Department of Italian Hospital for the help with tumor sample collection This research was supported by grants from the National Agency of Scientific and Technological Promotion FONCYT PICT 200601915 Argentina Grant PIP2011 166 from the National Council of Scientific and Technical Research CONICET PIP 2011/2013 Argentina Roemmers Foundation 2009–2011 Argentina and Florencio Fiorini Foundation 2013 Argentina and René Barón Foundation 2015 ArgentinaAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards Moreover we have obtained a statement of informed consent to publish from the participant or legal parent or guardian for children to report individual patient data
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