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Architectural patterns of p16 immunohistochemical expression associated with cancer immunity and prognosis of head and neck squamous cell carcinoma

 Hyang Joo Ryu  ;  Eun Kyung Kim  ;  Su Jin Heo  ;  Byoung Chul Cho  ;  Hye Ryun Kim  ;  Sun Och Yoon 
 APMIS, Vol.125(11) : 974-984, 2017 
Journal Title
Issue Date
Aged ; Antigens, CD/genetics ; Antigens, CD/immunology ; Antigens, Differentiation, Myelomonocytic/genetics ; Antigens, Differentiation, Myelomonocytic/immunology ; Biomarkers, Tumor/genetics* ; Biomarkers, Tumor/immunology ; CD3 Complex/genetics ; CD3 Complex/immunology ; CD8 Antigens/genetics ; CD8 Antigens/immunology ; Carcinoma, Squamous Cell/diagnosis* ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/mortality ; Carcinoma, Squamous Cell/pathology ; Cyclin-Dependent Kinase Inhibitor p16/genetics* ; Cyclin-Dependent Kinase Inhibitor p16/immunology ; Female ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/immunology ; Gene Expression ; Head and Neck Neoplasms/diagnosis* ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/mortality ; Head and Neck Neoplasms/pathology ; Human papillomavirus 16/growth & development ; Human papillomavirus 16/pathogenicity ; Humans ; Male ; Middle Aged ; Papillomavirus Infections/diagnosis* ; Papillomavirus Infections/genetics ; Papillomavirus Infections/mortality ; Papillomavirus Infections/pathology ; Prognosis ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/immunology ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/immunology ; Survival Analysis
Squamous cell carcinoma ; cancer immunity ; head and neck ; human papilloma virus ; p16 ; prognosis
We evaluated the expression patterns of p16, which is used as a surrogate marker of HPV infection in head and neck squamous cell carcinoma (HNSCC), in regard to their biological and prognostic implications. p16 expression patterns and infiltrated immune cells were analyzed through immunohistochemistry of p16, CD3, CD8, PD-1, FOXP3, and CD163 on surgically resected HNSCCs (n = 393). Patterns of p16 immunoexpression were defined as STRONG (strong, diffuse expression in cytoplasm, and nucleus in >70% of tumor cells), MARGINAL (expression restricted to tumor margins), MOSAIC (ragged, discontinued expression), NUCLEAR (expression in nuclei only), and ABSENT (no expression). The STRONG pattern was more frequent in the oropharynx, and the MARGINAL pattern was noted only in the oral cavity. MOSAIC and NUCLEAR patterns were noted at variable sites. No two patterns of p16 expression showed the same immune cell composition of CD3+ T cells, CD8+ cytotoxic T cells, PD-1+ T cells, FOXP3+ regulatory T cells, and CD163+ macrophages. In overall and disease-free survival analyses, the STRONG pattern showed the most favorable prognosis, while the NUCLEAR pattern had the worst prognosis. HNSCC anatomical sites, tumor-related immune cell components, and patient outcomes were associated with p16 expression patterns. Each architectural pattern of p16 expression may be related to different biological and prognostic phenotypes.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eun Kyung(김은경)
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Yoon, Sun Och(윤선옥) ORCID logo https://orcid.org/0000-0002-5115-1402
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Heo, Su Jin(허수진) ORCID logo https://orcid.org/0000-0002-0615-5869
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