The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Prognostic implications of stromal hyaluronic acid protein expression in resected oropharyngeal and oral cavity cancers

  • Sun, Der Sheng (Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Won, Hye Sung (Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Hong, Soon Auck (Department of Pathology, Soonchunhyang University Cheonan Hospital) ;
  • Hong, Ji Hyung (Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Jo, Heejoon (Department of Biostatistics, University of North Carolina at Chapel Hill) ;
  • Lee, Heejin (Cancer Research Institute, College of Medicine, The Catholic University of Korea) ;
  • Kim, Okran (Cancer Research Institute, College of Medicine, The Catholic University of Korea) ;
  • Lee, Myung Ah (Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Ko, Yoon Ho (Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
  • Received : 2018.06.09
  • Accepted : 2018.08.14
  • Published : 2020.03.01
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Abstract

Background/Aims: Hyaluronic acid (HA) regulates cell adhesion, migration and proliferation in various cancers. The clinical implications of HA in resected head and neck squamous cell carcinoma have not been elucidated. We investigated the clinical significance and prognostic value of the expression of tumoral and stromal HA and its related proteins in oropharyngeal and oral cavity cancer. Methods: Resected tissues from oropharyngeal or oral cavity cancer patients undergoing surgery were analysed in tissue microarrays divided into stroma and cancer panels. The expression levels of HA, HA synthases and hyaluronidases were also assessed by immunohistochemistry. Results: A total of 160 resected oropharyngeal or oral cavity cancer tissues were analysed. Stromal HA expression was observed more frequently in human papilloma virus (HPV)-negative tumors, but other clinicopathological characteristics did not differ. In patients with HPV-negative oral cavity cancers, high stromal HA expression was associated with significantly shorter recurrence-free survival and overall survival compared with low stromal HA expression. The expression of HA in both tumors and stroma was significantly correlated with poorer outcomes than other combinations in patients with HPV-negative oral cavity cancers. However, these prognostic roles of HA were not observed in patients with HPV-negative oropharyngeal cancers. In the HPV-stratified multivariate analysis, high stromal HA expression remained an independent indicator of poor prognosis in terms of recurrence-free survival. Conclusions: High stromal HA and expression of HA in both tumors and stroma were correlated with poor prognosis in HPV-negative oral cavity cancer, but not in HPV-negative oropharyngeal cancers.

Keywords

Acknowledgement

This study was supported by the Basic Science Research Pro-gram through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2015R1C1A1A01054591) (Yoon Ho Ko) and by The Catholic University of Korea Uijeongbu St. Mary's Hospital Clinical Research Laboratory Foundation made in the program year of 2013 (Yoon Ho Ko).

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