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Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection
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Yoon Ah Cho, Ji Myung Chung, Hyunmi Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
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Cancer Res Treat. 2019;51(3):1052-1063. Published online October 24, 2018
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DOI: https://doi.org/10.4143/crt.2018.411
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 Abstract
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- Purpose
The relationship between head and neck squamous cell carcinoma (HNSCC) and subtypes of tropomyosin-related kinase (Trk) has not been studied in-depth. In this study, we evaluated the expression patterns of TrkA, TrkB, and panTrk and their clinicopathological significance as well as association with p16 expression and human papilloma virus (HPV) status.
Materials and Methods
Total of 396 radically resected oropharyngeal (n=121) and non-oropharyngeal (n=275) HNSCCs were included. Immunohistochemistry for TrkA, TrkB, and panTrk was performed. In addition, p16 immunohistochemistry was performed to assess the HPV status. Using HPV-negative HNSCC cell lines, FaDu and CAL27, HPV type 16 E6/E7 gene was transfected, and then changes of TrkA and TrkB expression were analyzed.
Results
In the clinical samples of HNSCC, high expression of TrkA and panTrk were more associated with oropharyngeal and p16 positive squamous cell carcinoma (SCC). In patients with completely resected (R0-resected) oropharyngeal SCC, high TrkA expression was related to superior overall survival and recurrence-free survival (RFS). In patients with R0-resected oral cavity SCC, high panTrk was related to poor RFS. In HPV type E6/E7 gene-transfected FaDu and CAL27 cell lines, increase of TrkA expression was observed.
Conclusion
It seems that expression pattern of panTrk and TrkA differed according to anatomical sites of HNSCC and was closely related to p16 expression and patient prognosis. Trk expression should be considered in the context of anatomical site, p16 expression or HPV status and Trk subtypes.
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Citations
Citations to this article as recorded by  - NTRK Gene Expression Analysis in Oral Squamous Cell Carcinoma Mexican Population
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Molecular Cancer Research.2021; 19(1): 14. CrossRef - Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer
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Journal of Translational Medicine.2021;[Epub] CrossRef - Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma
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Pathology & Oncology Research.2020; 26(4): 2587. CrossRef - Overexpression of wild type or a Q311E mutant MB21D2 promotes a pro‐oncogenic phenotype in HNSCC
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Molecular Oncology.2020; 14(12): 3065. CrossRef - NOVA1 induction by inflammation and NOVA1 suppression by epigenetic regulation in head and neck squamous cell carcinoma
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Scientific Reports.2019;[Epub] CrossRef - Characterization of head and neck squamous cell carcinoma arising in young patients: Particular focus on molecular alteration and tumor immunity
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