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Aberrant expression of p53, p16(INK4a) and Ki-67 as basic biomarker for malignant progression of oral leukoplakias.
MedLine Citation:
PMID:  21435003     Owner:  NLM     Status:  Publisher    
J Oral Pathol Med (2011) Background:  The risk of malignant progression of oral leukoplakia with and without dysplasia is unpredictable. Materials and methods:  Leukoplakias without dysplasia of 35 patients, leukoplakias with dysplasia of 4 patients, and similar lesions obtained from tumor patients were retrospectively examined by immunohistochemistry for the expression of the proteins pRb, p53, p16(INK4a) , Cyclin D1 and Ki-67. The predictive power of combined aberrant expression patterns for the progression of leukoplakias without dysplasia was examined. Results:  Increased expression of p53, Ki-67 and Cyclin D1, and loss of p16(INK4a) occurred in 45.9%, 38.9%, 29.4% and 32.4% of the leukoplakias without dysplasia, respectively. All alterations increased with progression but had poor positive predictive value. However, the combined p53/p16(INK4a) /Ki-67 aberration occurred in only three (9%) cases, of which two patients (66.7%) experienced progression to dysplasia and carcinoma in situ. The combined p53/p16(INK4a) /Ki-67 alteration had a negative predictive value (NPV) and sensitivity of 100%, specificity of 97% and positive predictive value (PPV) of 67%. By contrast, the combined p53/p16(INK4a) /Cyclin D1 alteration had 97% NPV and sensitivity of 50%, specificity of 90% and only 25% PPV. Loss of pRb and concomitant overexpression of p16(INK4a) were not observed arguing against an involvement of HPV in oral leukoplakia. Conclusions:  We propose the combined p53/p16(INK4a) /Ki-67 alteration as a basic marker to define high risk leukoplakia patients. Lesions not showing this alteration appear to be harmless. Future studies should validate these findings and search for proteins which can further improve the PPV of the proposed basic marker.
Wasim Nasser; Christa Flechtenmacher; Dana Holzinger; Christof Hofele; Franz X Bosch
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-25
Journal Detail:
Title:  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology     Volume:  -     ISSN:  1600-0714     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8911934     Medline TA:  J Oral Pathol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 John Wiley & Sons A/S.
Department of Oral and Maxillofacial Surgery, University Hospital Heidelberg, Heidelberg, Germany Institute of Pathology, Heidelberg University, Heidelberg, Germany Molecular Biology Laboratory, Department of Otolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Heidelberg, Germany.
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