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The p16INK4a expression in human papillomavirus-associated oral squamous cell carcinoma in northeastern Thai population
Piyawut Swangphon, B.Sc.1, Chamsai Pientong, M.D., Dr.Sc.Hum.1, Miriam Reuschenbach, M.D., Ph.D.2, Magnus von Knebel Doeberitz, M.D., Ph.D.2 and Tipaya Ekalaksananan, M.Sc., M.D.1
1 Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
2 Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
Abstract
Background: Overexpression of p16INK4a protein that is associated with E7 overproduction from high-risk human papillomavirus (HR-HPV) infection, has been well known as a biomarker for diagnosis of HPV associated abnormal cervical tissue and cervical cancer development. Previous studies reported that subset of oral squamous cell carcinoma (OSCC), which shows good prognosis of treatment, is involved by HR-HPV infection. To identify HR-HPV associated OSCC by p16INK4a protein biomarker, this study investigated the HPV prevalence and p16INK4a expression in oral tissue from OSCC cases.
Methods: The formalin-fixed paraffin-embedded (FFPE) oral tissues including 148 OSCC and 6 no-squamous intraepithelial lesions (no-SIL) were studied. All samples were extracted for DNA, which was qualified by polymerase chain reaction (PCR) using housekeeping gene, β-globin. The qualified DNA was investigated for HPV-DNA by PCR using primers HPV GP5+/6+ and p16INK4a protein expression was determined by immunohistochemical staining (IHC) and characterized into four patterns according to positive staining in nucleus and/or cytoplasm of tumor cells.
Results: The prevalence of HPV infection was 16.89% (25/148) and 0% (0/6) in OSCC cases and no-SIL group, respectively. The p16INK4a protein positive staining was characterized into four patterns according to staining in nuclease and/or cytoplasm of tumor cells including grade 0 (62.2%), grade 1 (6.1%), grade 2 (10.1%) and grade 3 (21.6%). The p16INK4a expression grade 3 was detected in 1 case of no-SIL group. The patterns of p16INK4a expression found in all of 25 HPV positive cases were grade 0 (52%, 13/25), grade 2 (20%, 5/25 and grade 3 (28%, 7/25). No significant correlation was detected between p16INK4a expression and HPV infection in oral tissues.
Conclusion: These result demonstrated that the p16INK4a expression in OSCC was not correlated with HPV infection and stated that p16INK4a is not really a good marker for HPV associated oral mucosal dysplasia or malignant transformation. The mechanisms which control p16INK4a expression should be further investigated. |
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