TY - JOUR
T1 - Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma
T2 - Validation of three-class hypothesis
AU - Weinberger, Paul M.
AU - Yu, Ziwei
AU - Kountourakis, Panteleimon
AU - Sasaki, Clarence
AU - Haffty, Bruce G.
AU - Kowalski, Diane
AU - Merkley, Mark A.
AU - Rimm, David L.
AU - Camp, Robert L.
AU - Psyrri, Amanda
N1 - Funding Information:
Sponsorships : Supported by Yale School of Medicine Institutional startup funds (AP), the Virginia Alden Wright Fund (CS), and a CORE Resident Research Grant #2006–26357 from the American Academy of Otolaryngology/Head and Neck Surgery (PMW). The funding sources had no involvement in the study design, data collection and analysis, interpretation of the data, writing of the manuscript, or decision to submit for publication.
PY - 2009/9
Y1 - 2009/9
N2 - Objective: The purpose of this study was to determine if oropharyngeal squamous cell carcinoma (OSCC) classified into three groups based on human papillomavirus (HPV) 16 DNA presence and p16 expression display different protein expression patterns. Study Design: Cross-sectional study. Setting: A laboratory-based study of patients with OSCC treated at a tertiary care academic medical center. Subjects and Methods: Paraffin-embedded OSCC specimens from 77 patients classified into the three-class model (HPV negative, HPV inactive [HPV16+/p16-], and HPV active [HPV16+/p16+]) were queried for the expression of 14 tumor progression proteins using AQUA (HistoRx, New Haven CT). Protein expression between groups was assessed by analysis of variance. Global expression patterns were determined by unsupervised hierarchical clustering. Results: There were significant differences in expression of β-catenin (P = 0.009), epidermal growth factor receptor (P = 0.009), and vascular endothelial growth factor (P = 0.028) between groups. HPV-active tumors had overexpression of β-catenin. Hierarchical clustering showed HPV-negative and HPV-inactive tumors displayed association patterns distinct from HPV-active tumors. Conclusions: Tumors classified by HPV DNA presence and p16 expression have different molecular phenotypes. This is the first demonstration of overexpression of β-catenin (also found in HPV-caused cervical cancer) in HPV-active OSCC. HPV-active OSCC may share a similar ontogeny to HPV-caused cervical cancer.
AB - Objective: The purpose of this study was to determine if oropharyngeal squamous cell carcinoma (OSCC) classified into three groups based on human papillomavirus (HPV) 16 DNA presence and p16 expression display different protein expression patterns. Study Design: Cross-sectional study. Setting: A laboratory-based study of patients with OSCC treated at a tertiary care academic medical center. Subjects and Methods: Paraffin-embedded OSCC specimens from 77 patients classified into the three-class model (HPV negative, HPV inactive [HPV16+/p16-], and HPV active [HPV16+/p16+]) were queried for the expression of 14 tumor progression proteins using AQUA (HistoRx, New Haven CT). Protein expression between groups was assessed by analysis of variance. Global expression patterns were determined by unsupervised hierarchical clustering. Results: There were significant differences in expression of β-catenin (P = 0.009), epidermal growth factor receptor (P = 0.009), and vascular endothelial growth factor (P = 0.028) between groups. HPV-active tumors had overexpression of β-catenin. Hierarchical clustering showed HPV-negative and HPV-inactive tumors displayed association patterns distinct from HPV-active tumors. Conclusions: Tumors classified by HPV DNA presence and p16 expression have different molecular phenotypes. This is the first demonstration of overexpression of β-catenin (also found in HPV-caused cervical cancer) in HPV-active OSCC. HPV-active OSCC may share a similar ontogeny to HPV-caused cervical cancer.
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U2 - 10.1016/j.otohns.2009.04.014
DO - 10.1016/j.otohns.2009.04.014
M3 - Article
C2 - 19716018
AN - SCOPUS:68949212920
SN - 0194-5998
VL - 141
SP - 382-389.e1
JO - Otolaryngology - Head and Neck Surgery
JF - Otolaryngology - Head and Neck Surgery
IS - 3
ER -
