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Tumour expressions of hypoxic markers predict the response to neo-adjuvant chemotherapy in children with inoperable rhabdomyosarcoma.
- Source :
-
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals [Biomarkers] 2019 Sep; Vol. 24 (6), pp. 538-548. Date of Electronic Publication: 2019 May 31. - Publication Year :
- 2019
-
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.
- Subjects :
- Adolescent
Antigens, Neoplasm metabolism
Biomarkers, Tumor metabolism
Biopsy
Carbonic Anhydrase IX metabolism
Carboplatin therapeutic use
Chemotherapy, Adjuvant methods
Child
Child, Preschool
Dactinomycin therapeutic use
Epirubicin therapeutic use
Female
Gene Expression
Glucose Transporter Type 1 metabolism
Humans
Hypoxia diagnosis
Hypoxia drug therapy
Hypoxia genetics
Hypoxia mortality
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Ifosfamide therapeutic use
Infant
Infant, Newborn
Male
Muscle Neoplasms diagnosis
Muscle Neoplasms genetics
Muscle Neoplasms mortality
Neoadjuvant Therapy methods
Prognosis
Prospective Studies
Rhabdomyosarcoma, Alveolar diagnosis
Rhabdomyosarcoma, Alveolar genetics
Rhabdomyosarcoma, Alveolar mortality
Rhabdomyosarcoma, Embryonal diagnosis
Rhabdomyosarcoma, Embryonal genetics
Rhabdomyosarcoma, Embryonal mortality
Survival Analysis
Treatment Outcome
Vascular Endothelial Growth Factor A metabolism
Vincristine therapeutic use
Antigens, Neoplasm genetics
Biomarkers, Tumor genetics
Carbonic Anhydrase IX genetics
Glucose Transporter Type 1 genetics
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Muscle Neoplasms drug therapy
Rhabdomyosarcoma, Alveolar drug therapy
Rhabdomyosarcoma, Embryonal drug therapy
Vascular Endothelial Growth Factor A genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1366-5804
- Volume :
- 24
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals
- Publication Type :
- Academic Journal
- Accession number :
- 30995126
- Full Text :
- https://doi.org/10.1080/1354750X.2019.1606275