HPV integration begins in the tonsillar crypt and leads to the alteration of p16, EGFR and c-myc during tumor formation

被引:159
作者
Kim, Se-Heon
Koo, Bon-Seok
Kang, Suki
Park, Kyeongmee
Kim, Haeryoung
Lee, Kyung Ryul
Lee, Moo Joo
Kim, Jong Man
Choi, Eun Chang
Cho, Nam Hoon
机构
[1] Yonsei Univ, Coll Med, Dept Pathol, Seoul, South Korea
[2] Yonsei Univ, Coll Med, Dept Otorhinolaryngol, Seoul, South Korea
[3] Inje Univ, Sanggye Paik Hosp, Dept Pathol, Seoul, South Korea
[4] Seoul Natl Univ, Bundang Hosp, Dept Pathol, Seoul, South Korea
[5] Biocore Inc, Seoul, South Korea
关键词
human papillomavirus; integration; tonsil cancer; p16; epidermal growth factor receptor;
D O I
10.1002/ijc.22464
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The prevalence of human papillomavirus (HPV) infection is high in the oropharyngeal mucosal regions, of which the tonsil is the most commonly affected. There may be a link between HPV and the pathogenesis of tonsillar cancer (TC), because of common anatomical characteristics between cervical and tonsillar cancer. We aimed to clarify whether HPV directly affects the oncogenesis and biologic behavior of TC by making a comparison between infection prevalence, physical status and viral loading numbers, and clinicopathologic prognostic factors. To compare HPV-related molecules between TC and tonsillitis (CFT), p16, survivin, HIF-1 alpha, skp-1, cyclin A, cyclin B1, c-myc and EGFR were investigated. We observed a significant difference in HPV prevalence between 52 TCs and 69 CFTs (73.1% vs. 11.6%), and most of the HPVs were type 16 (87.2%) and nonepisomal (94.1%). Most TCs associated with HPV arose from the tonsillar crypts, and tended to be inverted and poorly differentiated. Compared with HPV-negative TC, HPV-positive TC showed a strong association with p16 overexpression (P < 0.0001), and an inverse association with EGFR amplification (p = 0.0478). HPV-16 integration status was strongly associated with c-myc amplification (p = 0.034) and HIF-1 alpha overexpression (p = 0.022). HPV-16 integration could be directly related to tonsillar carcinogenesis initially in tonsillar crypts, followed by cell cycle aberration such as p16 overexpression related to the G1-S phase. (c) 2007 Wiley-Liss, Inc.
引用
收藏
页码:1418 / 1425
页数:8
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