Use of tissue microarray to facilitate oncology research.
HPV-positive oropharyngeal squamous cell carcinomas (OSCC) represent a distinct disease entity from traditional OSCC. We hypothesized that for HPV DNA-positive cases, p16 expression status differentiates the biologically relevant ones.We determined HPV16DNA viral load in a cohort of 79 oropharyngeal squamous cell cancers by real-time polymerase chain reaction (PCR). We used cervical cancer as a disease model for HPV-initiated epithelial cancer. In cervical cancer, p53 and Rb expression is reduced, while p16 expression is increased. We used TMA technology to facilitate interrogation of this cohort for p53, Rb, and p16 protein expression using a quantitative, in situ method of protein analysis (AQUA analysis). Our results indeed delineate three biologically and clinically distinct types of oropharyngeal squamous cell cancers based on HPV-DNA determination and p16 expression status: one class of HPV-negative/p16-nonexpressing (HPV-negative), one class of HPV-positive/p16-nonexpressing (HPV-inactive), and one class of HPV positive/p16-expressing (HPV-active) oropharyngeal tumors. We demonstrated that only the HPV-active tumors share a similar molecular phenotype to cervical cancers, and are the ones associated with favorable prognosis.
Gouveris
Panagiotis
P
Division of Hematology Oncology, Department of Internal Medicine, Yale University, New Haven, CT, USA.
Weinberger
Paul M
PM
Psyrri
Amanda
A
D035843:Biomedical Research / Q000379:methods*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000473:pathology* / Q000821:virology*; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D052162:Human papillomavirus 16 / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D007150:Immunohistochemistry; D008495:Medical Oncology; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology* / Q000821:virology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D013997:Time Factors; D046888:Tissue Array Analysis / Q000191:economics / Q000379:methods*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D019562:Viral Load
D004279:DNA, Viral