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Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma: validation of three-class hypothesis.
Otolaryngol Head Neck Surg. 2009 Sep; 141(3):382-9.OH

Abstract

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 beta-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 beta-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 beta-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.

Authors+Show Affiliations

Department of Otolaryngology, Medical College of Georgia, Augusta, GA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19716018

Citation

Weinberger, Paul M., et al. "Defining Molecular Phenotypes of Human Papillomavirus-associated Oropharyngeal Squamous Cell Carcinoma: Validation of Three-class Hypothesis." Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery, vol. 141, no. 3, 2009, pp. 382-9.
Weinberger PM, Yu Z, Kountourakis P, et al. Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma: validation of three-class hypothesis. Otolaryngol Head Neck Surg. 2009;141(3):382-9.
Weinberger, P. M., Yu, Z., Kountourakis, P., Sasaki, C., Haffty, B. G., Kowalski, D., Merkley, M. A., Rimm, D. L., Camp, R. L., & Psyrri, A. (2009). Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma: validation of three-class hypothesis. Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery, 141(3), 382-9. https://doi.org/10.1016/j.otohns.2009.04.014
Weinberger PM, et al. Defining Molecular Phenotypes of Human Papillomavirus-associated Oropharyngeal Squamous Cell Carcinoma: Validation of Three-class Hypothesis. Otolaryngol Head Neck Surg. 2009;141(3):382-9. PubMed PMID: 19716018.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defining molecular phenotypes of human papillomavirus-associated oropharyngeal squamous cell carcinoma: 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, PY - 2008/09/20/received PY - 2009/02/25/revised PY - 2009/04/16/accepted PY - 2009/9/1/entrez PY - 2009/9/1/pubmed PY - 2009/10/10/medline SP - 382 EP - 9 JF - Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery JO - Otolaryngol Head Neck Surg VL - 141 IS - 3 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 beta-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 beta-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 beta-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. SN - 0194-5998 UR - https://www.unboundmedicine.com/medline/citation/19716018/Defining_molecular_phenotypes_of_human_papillomavirus_associated_oropharyngeal_squamous_cell_carcinoma:_validation_of_three_class_hypothesis_ L2 - http://journals.sagepub.com/doi/full/10.1016/j.otohns.2009.04.014?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -