CC BY-NC-ND 4.0 · Laryngorhinootologie 2019; 98(S 02): S80
DOI: 10.1055/s-0039-1686050
Abstracts
Oncology

Analysis of CpG promotor methylation status of the AKR1C3 gene in HPV16 positive and negative oropharyngeal squamous cell carcinoma

B Pulido Guevara
1   Klinik und Poliklinik für HNO-Heilkunde, Kopf- und Halschiru, Köln
,
N Würdemann
2   Klinik und Poliklinik für HNO-Heilkunde, Kopf- und Halschirurgie, Medizinische Fakultät, Universität zu, Köln
,
E Groß
3   Universität zu Köln, Köln
,
OG Siefer
4   Jean-Uhrmacher-Institut für klinische HNO-Forschung, Köln
,
S Wagner
5   Kopf-Hals-Tumorforschung, Klinik für HNO-Heilkunde, Kopf-/Halschirurgie, Justus-Liebig-Universität, Gießen
,
HSF Reder
5   Kopf-Hals-Tumorforschung, Klinik für HNO-Heilkunde, Kopf-/Halschirurgie, Justus-Liebig-Universität, Gießen
,
S Gattenlöhner
6   Institut für Pathologie, Universitätsklinikum Gießen und Marburg GmbH, Gießen
,
CU Huebbers
4   Jean-Uhrmacher-Institut für klinische HNO-Forschung, Köln
,
JP Klußmann
2   Klinik und Poliklinik für HNO-Heilkunde, Kopf- und Halschirurgie, Medizinische Fakultät, Universität zu, Köln
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    Introduction:

    At least two subgroups of OPSCC (Oropharyngeal Squamous Cell Carcinoma) can be distinguished based on high-risk Human Papillomavirus (HPV) infection, namely HPV16. We showed that upregulation of Aldo-Keto-Reductases (AKR) 1C1 and 1C3 is strongly associated with poor prognosis irrespective of HPV-status. However, our data suggest that expression of these proteins might be induced by independent mechanisms in HPV+ and HPV-tumors.

    Methods:

    We performed a bioinformatic analysis of the AKR1C1-C4 promotor regions located on Chromosome 10p15 – 14 in a clinical cohort of patients preselected for good clinical response (n = 26) and appearance of local/distant recurrence (n = 26). AKR1C3 expression was confirmed by immunohistochemistry of 52 FFPE tumor samples from primary OPSCC (n = 26 HPV+, n = 26 HPV-) with additional n = 16 samples from corresponding lymph node metastases. Tumor regions were microdissected for DNA extraction and pyrosequencing was performed to determine methylation status of CpG islands in the promoter region of AKR1C3. Results were correlated with clinical and histopathological data.

    Results:

    The analysis revealed two promising CpG islands upstream of AKR1C3 correlating with potential C/EBP and SP-1 transcription factor binding sites. Upregulation of AKR1C3 showed poor prognosis for those tumors with unfavorable clinical response (p = 0.0024). CpG methylation analysis correlated with induction of AKR1C3 expression in HPV- but not HPV+ tumor samples.

    Conclusions:

    Our findings show that HPV-tumors presenting AKR1C3 expression correlated with methylation status of the identified CpG islands, whereas HPV-tumors without AKR1C3 expression did not. Protein expression in HPV+tumors might be regulated by an independent mechanism subject of ongoing analysis.


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    Barbara Pulido
    Uniklinik Köln,
    Kerpener Str. 62, 50937
    Köln

    Publication History

    Publication Date:
    23 April 2019 (online)

    © 2019. The Author(s). 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 commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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