Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection.

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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DOI:
10.4143/crt.2018.411
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发表时间:
2019-07
影响因子:
4.6
通讯作者:
Yoon SO
Yoon SO
中科院分区:
医学2区
文献类型:
--
作者:
Cho YA;Chung JM;Ryu H;Kim EK;Cho BC;Yoon SO

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原肌球蛋白相关激酶(Trk)亚型与头颈部鳞状细胞癌(HNSCC)的关系尚未得到深入研究。在这项研究中,我们评估了TrkA,TrkB和panTrk的表达模式及其临床病理意义,以及与p16表达和人乳头瘤病毒(HPV)状态的关系。共纳入396例根治性切除的口咽(n=121)和非口咽(n=275)HNSCC。进行TrkA、TrkB和panTrk的免疫组织化学。此外,进行p16免疫组化以评估HPV状态。以HPV阴性的HNSCC细胞系FaDu和CAL 27为材料,转染HPV 16型E6/E7基因,分析TrkA和TrkB表达的变化。在HNSCC的临床标本中,TrkA和panTrk的高表达与口咽部和p16阳性的鳞状细胞癌(SCC)相关性更高。在口咽部鳞状细胞癌完全切除(R 0切除)患者中,TrkA高表达与上级总生存率和无复发生存率(RFS)相关。在R 0切除的口腔SCC患者中,高panTrk与RFS差相关。在HPV E6/E7型基因转染的FaDu和CAL 27细胞系中,观察到TrkA表达增加。结论p16蛋白在HNSCC中的表达与病理分级、临床分期、预后密切相关,p16蛋白在HNSCC中的表达与病理分级、临床分期密切相关。Trk表达应在解剖部位、p16表达或HPV状态和Trk亚型的背景下考虑。
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. 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. 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. 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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