Tumour expressions of hypoxic markers predict the response to neo-adjuvant chemotherapy in children with inoperable rhabdomyosarcoma
Malgorzata Anna Krawczyk, Malgorzata Styczewska ORCID Icon, Ewa M. Sokolewicz, Michal Kunc ORCID Icon, Anna Gabrych, Aleksandra Fatyga, show all
Received 22 Aug 2018, Accepted 05 Apr 2019, Accepted author version posted online: 17 Apr 2019, Published online: 31 May 2019
Download citation https://doi.org/10.1080/1354750X.2019.1606275
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Abstract
Objective: The study was to assess whether tumour expressions of hypoxia-inducible factor (HIF)-1α, glucose transporter (GLUT)-1, carbonic anhydrase (CA) IX and vascular endothelial growth factor (VEGF) predict response to neo-adjuvant chemotherapy (naCHT) in children with inoperable rhabdomyosarcoma (RMS).
Methods: Immunohistochemical expressions of hypoxia markers were determined semi-quantitatively in tumour tissue microarray of 46 patients with embryonal RMS (RME) and 20 with alveolar (RMA), treated with CWS protocols (1992–2013).
Results: In paediatric RME, response to naCHT was influenced significantly by tumour expression of CA IX and GLUT-1. Patients with RMA with low expressions of analysed markers responded well to naCHT, while all poor-responders expressed highly hypoxia markers. Only 5.88% of RMA and 11.11% of RME tumours did not express any of the proteins. In both RME and RMA subgroups, most poor-responders demonstrated simultaneous high expression of ≥3 markers, while most patients expressing ≤2 markers responded well to naCHT. In the whole cohort, co-expression of ≥3 markers, was the only independent factor predicting poor-response to chemotherapy (odds ratio 14.706; 95% CI 1.72–125.75; p = 0.014).
Conclusions: Immunohistochemical expression pattern of four endogenous markers of hypoxia, in tumour tissue at diagnosis, emerges as a promising tool to predict response to naCHT in children with inoperable RMS.
Keywords: HIF-1α, GLUT-1, CA IX, VEGF, response to neo-adjuvant chemotherapy, rhabdomyosarcoma, children
Malgorzata Anna Krawczyk, Malgorzata Styczewska ORCID Icon, Ewa M. Sokolewicz, Michal Kunc ORCID Icon, Anna Gabrych, Aleksandra Fatyga, show all
Received 22 Aug 2018, Accepted 05 Apr 2019, Accepted author version posted online: 17 Apr 2019, Published online: 31 May 2019
Download citation https://doi.org/10.1080/1354750X.2019.1606275
Select Language▼
Translator disclaimer
Abstract
Objective: The study was to assess whether tumour expressions of hypoxia-inducible factor (HIF)-1α, glucose transporter (GLUT)-1, carbonic anhydrase (CA) IX and vascular endothelial growth factor (VEGF) predict response to neo-adjuvant chemotherapy (naCHT) in children with inoperable rhabdomyosarcoma (RMS).
Methods: Immunohistochemical expressions of hypoxia markers were determined semi-quantitatively in tumour tissue microarray of 46 patients with embryonal RMS (RME) and 20 with alveolar (RMA), treated with CWS protocols (1992–2013).
Results: In paediatric RME, response to naCHT was influenced significantly by tumour expression of CA IX and GLUT-1. Patients with RMA with low expressions of analysed markers responded well to naCHT, while all poor-responders expressed highly hypoxia markers. Only 5.88% of RMA and 11.11% of RME tumours did not express any of the proteins. In both RME and RMA subgroups, most poor-responders demonstrated simultaneous high expression of ≥3 markers, while most patients expressing ≤2 markers responded well to naCHT. In the whole cohort, co-expression of ≥3 markers, was the only independent factor predicting poor-response to chemotherapy (odds ratio 14.706; 95% CI 1.72–125.75; p = 0.014).
Conclusions: Immunohistochemical expression pattern of four endogenous markers of hypoxia, in tumour tissue at diagnosis, emerges as a promising tool to predict response to naCHT in children with inoperable RMS.
Keywords: HIF-1α, GLUT-1, CA IX, VEGF, response to neo-adjuvant chemotherapy, rhabdomyosarcoma, children
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