Discrimination of 'Driver' and 'Passenger' HPV in Tonsillar Carcinomas by the Polymerase Chain Reaction, Chromogenic In Situ Hybridization, and p16 INK4a Immunohistochemistry

被引:24
作者
Evans M.F. [1 ]
Matthews A. [2 ]
Kandil D. [2 ]
Adamson C.S.-C. [1 ]
Trotman W.E. [1 ]
Cooper K. [1 ,2 ]
机构
[1] Department of Pathology, University of Vermont College of Medicine, Burlington
[2] Department of Pathology and Laboratory Medicine, Fletcher Allen Health Care, Burlington, VT
关键词
Human papillomavirus (HPV); p16 [!sup]INK4a[!/sup; Tonsillar carcinoma;
D O I
10.1007/s12105-011-0282-y
中图分类号
学科分类号
摘要
Human papillomavirus (HPV) positive tonsillar squamous cell carcinoma (TSCC) is associated with a favorable clinical outcome. However, the HPV detected in a given tumor may be causal (driver HPV) or an incidental bystander (passenger HPV). There is a need to discriminate these forms of HPV in TSCCs to understand their impact on HPV as a biomarker for use in TSCC patient management. This study has compared the polymerase chain reaction (PCR), chromogenic in situ hybridization (CISH), and p16 INK4a immunohistochemistry in the assessment of HPV status in TSCC. Archival specimens of TSCC from thirty patients were investigated. HPV was detected by PCR in 25/30 (83.3%) tumors; HPV16 (70.0%) and HPV52 (6.7%) were the most common types. HPV was corroborated by CISH in 22/25 (88.0%) specimens; integrated HPV was implicated by the presence of punctate signals in each of these cases. p16 INK4a staining was found in 20/22 (90.9%) HPV PCR positive samples; two PCR/CISH HPV positive cases were p16 INK4a negative and two HPV negative samples were p16 INK4a positive. These data suggest that a minority of HPV positive TSCCs are positive for passenger HPV and that two or more assays may be required for diagnosing driver HPV status. Further studies are required to exam whether oropharyngeal tumors positive for passenger HPV have a less favorable prognosis than tumors that are driver HPV positive. The clinical significance of TSCCs that test HPV negative/p16 INK4a positive, PCR and CISH HPV positive/p16 INK4a negative, or PCR HPV positive/p16 INK4a and CISH negative, also requires further investigation. © 2011 Springer Science+Business Media, LLC.
引用
收藏
页码:344 / 348
页数:4
相关论文
共 35 条
[1]  
Dahlgren L., Mellin H., Wangsa D., Et al., Comparative genomic hybridization analysis of tonsillar cancer reveals a different pattern of genomic imbalances in human papillomavirus-positive and -negative tumors, Int J Cancer, 107, pp. 244-249, (2003)
[2]  
Dahlstrand H., Nasman A., Romanitan M., Et al., Human papillomavirus accounts both for increased incidence and better prognosis in tonsillar cancer, Anticancer Res, 28, 2 B, pp. 1133-1138, (2008)
[3]  
Dahlstrand H., Dahlgren L., Lindquist D., Et al., Presence of human papillomavirus in tonsillar cancer is a favourable prognostic factor for clinical outcome, Anticancer Res, 24, pp. 1829-1835, (2004)
[4]  
Hafkamp H.C., Mooren J.J., Claessen S.M., Et al., P21 Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis, Mod Pathol, 22, pp. 686-698, (2009)
[5]  
Hammarstedt L., Lindquist D., Dahlstrand H., Et al., Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer, Int J Cancer, 119, pp. 2620-2623, (2006)
[6]  
Kuo K.T., Hsiao C.H., Lin C.H., Et al., The biomarkers of human papillomavirus infection in tonsillar squamous cell carcinoma-molecular basis and predicting favorable outcome, Mod Pathol, 21, pp. 376-386, (2008)
[7]  
Mellin H., Friesland S., Lewensohn R., Et al., Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival, Int J Cancer, 89, pp. 300-304, (2000)
[8]  
Mellin H., Dahlgren L., Munck-Wikland E., Et al., Human papillomavirus type 16 is episomal and a high viral load may be correlated to better prognosis in tonsillar cancer, Int J Cancer, 102, pp. 152-158, (2002)
[9]  
Syrjanen S., HPV infections and tonsillar carcinoma, J Clin Pathol, 57, pp. 449-455, (2004)
[10]  
Wittekindt C., Gultekin E., Weissenborn S.J., Dienes H.P., Pfister H.J., Klussmann J.P., Expression of p16 protein is associated with human papillomavirus status in tonsillar carcinomas and has implications on survival, Adv Otorhinolaryngol, 62, pp. 72-80, (2005)