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CC BY-NC-ND 4.0 · World J Nucl Med 2021; 20(03): 228-236
DOI: 10.4103/wjnm.WJNM_91_20
Original Article

Correlation between imaging and tissue biomarkers of hypoxia in squamous cell cancer of the head and neck

Shreya Kunder
Department of Radiation Oncology, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai
,
Abhishek Chatterjee
Department of Radiation Oncology, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai
,
Subhakankha Manna
1   Mahimkar Lab, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai
,
Manoj Mahimkar
1   Mahimkar Lab, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai
,
Asawari Patil
2   Department of Pathology, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai
,
Venkatesh Rangarajan
3   Department of Nuclear Medicine & Molecular Imaging, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai
,
Ashwini Budrukkar
Department of Radiation Oncology, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai
,
Sarbani Ghosh-Laskar
Department of Radiation Oncology, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai
,
Jai Prakash Agarwal
Department of Radiation Oncology, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai
,
Tejpal Gupta
Department of Radiation Oncology, Advanced Centre for Treatment Research & Education in Cancer (ACTREC)/Tata Memorial Hospital (TMH), Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai
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Abstract

The aim of this study was to correlate endogenous tissue biomarkers of hypoxia with quantitative imaging parameters derived from 18F-fluoro-misonidazole (F-MISO) and 18F-fluoro-deoxy-glucose (FDG) positron emission tomography/computed tomography (PET/CT) and clinical outcomes in locoregionally advanced head and neck squamous cell carcinoma (HNSCC). Tumor-tissue blocks of HNSCC patients with pretreatment F-MISO-PET/CT and FDG-PET/CT were de-archived for expression of hypoxia-inducible factor-1 alpha (HIF-1α) subunit, carbonic anhydrase-IX (CA-IX), and glucose transporter subunit-1 (GLUT-1) using immunohistochemistry (IHC). The intensity of staining was graded and correlated with quantitative imaging parameters and with disease-related outcomes. Tissue blocks were analyzed for 14 of 20 patients. On IHC, median H-scores for HIF-1α, CA-IX, and GLUT-1 were 130, 0, and 95, respectively. No significant correlation of tissue biomarkers of hypoxia with quantitative imaging parameters was found. However, borderline significant correlation was seen for H-scores of CA-IX with hypoxic tumor volume (HTV) (r = 0.873, P = 0.054) and fractional hypoxic volume (r = 0.824, P = 0.086) derived from F-MISO-PET/CT. At a median follow-up of 43 months, 5-year Kaplan–Meier estimates of locoregional control, disease-free survival, and overall survival were 53%, 43%, and 40%, respectively. Increased expression of HIF-1α or GLUT-1 (dichotomized by median H-scores) was not individually associated with disease-related outcomes. However, a combination of high HTV (>4.89cc) with above median H-scores of either HIF-1α (>130) and/or GLUT-1 (>95) was associated with worse clinical outcomes. None of the three patients with such “adverse hypoxic profile” were long-term survivors. There is no significant correlation of endogenous tissue biomarkers of hypoxia (HIF-1α, CA-IX, and GLUT-1) with quantitative imaging parameters (on F-MISO-PET/CT and FDG-PET/CT) or long-term outcomes in HNSCC. However, a combination of both can identify a subgroup of patients with adverse outcomes.

Keywords

And imaging - biomarkers - head–neck cancer - hypoxia - immunohistochemistry

Financial support and sponsorship

All functional imagings as well as IHC for assessment of tissue biomarkers on the study were funded through competitive intramural research grants from Tata Memorial Centre, Mumbai, India. The sponsor, however, had no role in the study design, conduct, data collection, analysis, or reporting of results.




Publication History

Received: 04 July 2020

Accepted: 11 January 2021

Article published online:
24 March 2022

© 2021. Sociedade Brasileira de Neurocirurgia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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