Glut-1 expression in small cervical biopsies is prognostic in cervical cancers treated with chemoradiation

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Kanjanapan, Y; Deb, S; Young, RJ; Bressel, M; Mileshkin, L; Rischin, D; Hofman, MS; Narayan, K; Siva, SDate
2017-02-01Source Title
Clinical and Translational Radiation OncologyPublisher
ELSEVIER IRELAND LTDUniversity of Melbourne Author/s
Hofman, Michael; Rischin, Danny; Siva, Shankar; Mileshkin, Linda; Narayan, KailashAffiliation
Medical EducationObstetrics and Gynaecology
Medicine and Radiology
Sir Peter MacCallum Department of Oncology
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Kanjanapan, Y., Deb, S., Young, R. J., Bressel, M., Mileshkin, L., Rischin, D., Hofman, M. S., Narayan, K. & Siva, S. (2017). Glut-1 expression in small cervical biopsies is prognostic in cervical cancers treated with chemoradiation. CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY, 2, pp.53-58. https://doi.org/10.1016/j.ctro.2017.01.003.Access Status
Open AccessAbstract
Background/purpose: Chemoradiation (CRT) is standard therapy for locally advanced cervical cancer (LACC). However, there is a lack of biomarkers to identify patients at high relapse-risk. We examine metabolic (glucose transporter-1 [Glut-1]), hypoxic (hypoxia inducible factor [HIF-1α]; carbonic anhydrase [CA-9]) and proliferative (Ki-67) markers for prognostic utility in LACC. Materials/methods: 60 LACC patients treated with CRT had pre-treatment biopsies. Immunohistochemistry was performed for Glut-1, HIF-1a and CA-9, to generate a histoscore from intensity and percentage staining; and Ki-67 scored by percentage of positive cells. For each biomarker, treatment response and survival was compared between low and high-staining groups by logrank testing and multivariate analyses. Results: High Glut-1 expression was associated with inferior progression-free survival (PFS), (hazard ratio [HR] 2.8, p = 0.049) and overall survival (OS), (HR 5.0, p = 0.011) on multifactor analysis adjusting for stage, node positivity, tumour volume and uterine corpus invasion. High Glut-1 correlated with increased risk of distant failure (HR 14.6, p = 0.001) but not local failure. Low Glut-1 was associated with higher complete metabolic response rate on post-therapy positron emission tomography scan (odds ratio 3.4, p = 0.048). Ki-67 was significantly associated with PFS only (HR 1.19 per 10 units increase, p = 0.033). Biomarkers for hypoxia were not associated with outcome. Conclusions: High Glut-1 in LACC is associated with poor outcome post CRT. If prospectively validated, Glut-1 may help select patients for more intensive treatment regimens.
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