Immunohistochemical overexpression of hypoxia-induced factor 1α associated with slow reduction in 18fluoro-2-deoxy-D-glucose uptake for chemoradiotherapy in patients with pharyngeal cancer

  • Shang-Wen Chen
  • Ying-Chun Lin
  • Rui-Yun Chen
  • Te-Chun Hsieh
  • Kuo-Yang Yen
  • Ji-An Liang
  • Shih-Neng Yang
  • Yao-Ching Wang
  • Ya-Huey Chen
  • Nan-Haw Chow
  • Chia-Hung KaoEmail author
Original Article



This study examined genomic factors associated with a reduction in 18fluoro-2-deoxy-D-glucose (FDG) uptake during positron emission tomography–computed tomography (PET-CT) for definitive chemoradiotherapy (CRT) in patients with pharyngeal cancer.


The pretreatment and interim PET-CT images of 25 patients with advanced pharyngeal cancers receiving definitive CRT were prospectively evaluated. The maximum standardized uptake value (SUVmax) of the interim PET-CT and the reduction ratio of the SUVmax (SRR) between the two images were measured. Genomic data from pretreatment incisional biopsy specimens (SLC2A1, CAIX, VEGF, HIF1A, BCL2, Claudin-4, YAP1, MET, MKI67, and EGFR) were analyzed using tissue microarrays. Differences in FDG uptake and SRRs between tumors with low and high gene expression were examined using the Mann–Whitney test. Cox regression analysis was performed to examine the effects of variables on local control.


The SRR of the primary tumors (SRR-P) was 0.59 ± 0.31, whereas the SRR of metastatic lymph nodes (SRR-N) was 0.54 ± 0.32. Overexpression of HIF1A was associated with a high iSUVmax of the primary tumor (P < 0.001) and neck lymph node (P = 0.04) and a low SRR-P (P = 0.02). Multivariate analysis revealed that patients who had tumors with low SRR-P or high HIF1A expression levels showed inferior local control.


In patients with pharyngeal cancer requiring CRT, HIF1A overexpression was positively associated with high interim SUVmax or a slow reduction in FDG uptake. Prospective trials are needed to determine whether the local control rate can be stratified using the HIF1A level as a biomarker and SRR-P.


Head and neck cancer Positron emission tomography 18Fluoro-2-deoxy-D-glucose Chemoradiotherapy Hypoxia-inducible factor 1α 



Carbonic anhydrase 9




Computed tomography




Glucose transporter 1, SLCAA1 gene provides instructions for producing Glut1


Head and neck squamous cell carcinoma


Positron emission tomography and computed tomography


Pretreatment maximum standardized uptake value


Interim maximum standardized uptake value


SUVmax reduction ratio


Vascular endothelial growth factor


Volume reduction ratio



Author contributions

CH Kao and SW Chen were responsible for design of the study. RY Chen, YC Lin, NH Chow, and KY Yen collected the data. RY Chen, YC Lin, and SW Chen carried out statistical analysis, interpretation of data, and drafting of the article. SN Yang, JA Liang, TC Hsieh, YC Wang, and YH Chen provided intellectual content. SW and CH Kao approved the version to be submitted for publication. SW Chen and YC Lin contributed equally. All authors read and approved the final manuscript.

Compliance with ethical standards


This study was funded in part by the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019); China Medical University Hospital; Academia Sinica Taiwan Biobank Stroke Biosignature Project (BM10501010037); NRPB Stroke Clinical Trial Consortium (MOST 104-2325-B-039 -005); Tseng-Lien Lin Foundation, Taichung, Taiwan; Taiwan Brain Disease Foundation, Taipei, Taiwan; the Katsuzo and Kiyo Aoshima Memorial Fund, Japan; and the China Medical University under the Aim for the Top University Plan of the Ministry of Education, Taiwan, and Health and Welfare surcharge of tobacco products, China Medical University Hospital Cancer Research Center of Excellence (MOHW105-TDU-B-212-134003, Taiwan). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All 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 Declaration of Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the institutional review board (IRB) of China Medical University (DMR99-IRB-010).

Informed consent

All patients provided informed consent before inclusion in this prospective study.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Shang-Wen Chen
    • 1
    • 4
    • 5
  • Ying-Chun Lin
    • 1
    • 3
  • Rui-Yun Chen
    • 2
  • Te-Chun Hsieh
    • 6
    • 7
  • Kuo-Yang Yen
    • 6
    • 7
  • Ji-An Liang
    • 1
    • 8
  • Shih-Neng Yang
    • 1
    • 7
  • Yao-Ching Wang
    • 1
  • Ya-Huey Chen
    • 9
    • 10
  • Nan-Haw Chow
    • 11
  • Chia-Hung Kao
    • 6
    • 8
    Email author
  1. 1.Department of Radiation OncologyChina Medical University HospitalTaichungTaiwan
  2. 2.Department of PathologyChina Medical University HospitalTaichungTaiwan
  3. 3.The Ph.D. Program for Cancer Biology and Drug DiscoveryChina Medical University and Academia SinicaTaichungTaiwan
  4. 4.School of MedicineChina Medical UniversityTaichungTaiwan
  5. 5.School of MedicineTaipei Medical UniversityTaipeiTaiwan
  6. 6.Department of Nuclear Medicine and PET CenterChina Medical University HospitalTaichungTaiwan
  7. 7.Department of Biomedical Imaging and Radiological ScienceChina Medical UniversityTaichungTaiwan
  8. 8.Graduate Institute of Clinical Medical Science, School of Medicine, College of MedicineChina Medical UniversityTaichungTaiwan
  9. 9.Graduate Institute of Cancer BiologyChina Medical UniversityTaichungTaiwan
  10. 10.Center for Molecular MedicineChina Medical University HospitalTaichungTaiwan
  11. 11.Department of PathologyNational Cheng Kung UniversityTainanTaiwan

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