Expression of p53, p63, podoplanin and Ki-67 in recurring versus non-recurring oral leukoplakia

Jonas Sundberg,Anikó Kovács,Sushma Pandey,Dipak Sapkota,Erik Holmberg,Lars Peter Sand,Jenny Öhman,Bengt Hasséus,Göran Kjeller,Burcu Tokozlu,Daniel Giglio

doi:10.1038/s41598-021-99326-5

Abstract

Oral leukoplakia (OL), a potentially malignant disorder, recurs in 40% of cases after surgical removal. Recurrence is a risk factor for malignant transformation. We aimed to examine the prognostic significance of four biomarkers related to cell proliferation: p53, p63, podoplanin (PDPN) and Ki-67 in predicting recurrence. Formalin-fixed-paraffin-embedded specimens from excised OL (n = 73, 33 recurrent; 40 non-recurrent) were collected in a prospective study. Immunohistochemistry was used to visualise expression of p53, p63, PDPN and Ki-67. Image analysis software was used for quantification of p53-, p63- and Ki-67-expressing cells, while PDPN was analysed visually. The expression of all four proteins were higher in recurrent compared with non-recurrent OL, only expression of p53 was statistically significant. In uni- and multivariable Cox regression analyses of individual markers, expression of p63 was significantly associated with higher recurrence risk (p = 0.047). OL with a combined high expression of both p53 and p63 had a significantly higher risk to recur [Log Rank, p = 0.036; multivariate Cox, HR: 2.48 (1.13–5.44; p = 0.024)]. Combination of p53 and p63 expression may be used as a prognostic biomarker for recurrence of OL.

Highlights

Oral leukoplakia (OL), a potentially malignant disorder, recurs in 40% of cases after surgical removal
Oral leukoplakia (OL) is an oral potentially malignant disorder (OPMD) and has the potential to transform into oral squamous cell carcinoma (OSCC)[1]
Five patients (15%) from the recurring OL (ROL) group were identified as smokers, compared with 8 patients (20%) from the non-recurring OL (NOL) group

Summary

Introduction

Oral leukoplakia (OL), a potentially malignant disorder, recurs in 40% of cases after surgical removal. We aimed to examine the prognostic significance of four biomarkers related to cell proliferation: p53, p63, podoplanin (PDPN) and Ki-67 in predicting recurrence. In uni- and multivariable Cox regression analyses of individual markers, expression of p63 was significantly associated with higher recurrence risk (p = 0.047). Neither clinical type nor dysplasia status is sufficient as sole markers for malignant transformation This lack of objectivity in the histopathological assessment has been pointed out and there is a need for reliable biomarkers to risk assess OL. P63 and p53 regulate cell proliferation and differentiation and may play a role in the malignant transformation of OL21. Both proteins should be feasible biomarker candidates for recurrence and cancer transformation of OL

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Conclusion