Predictive Role of p53 Protein as a Single Marker or Associated with ki67 Antigen in Oral Leukoplakia: A Retrospective Longitudinal Study

Abstract

Oral leukoplakia (OL) is the most common potentially malignant lesion of the oral cavity. Immunohistochemical analysis of p53 and Ki67 proteins is a simple and inexpensive method widely used in non-dysplastic OLs to reveal lesions predicted to develop oral cancer. The present longitudinal study evaluated the predictive role of p53 and Ki67 proteins alone or in combination in a group of OLs without dysplasia followed for many years. Seventy-seven OL patients referred to our Department between January 2006 and October 2013 underwent histochemical analysis of p53 and Ki67 expression. OLs were considered at high risk in the presence of either high p53 expression (>20%), or low/normal p53 expression associated with high Ki67 expression (Ki67/p53 ratio >3). Seven OLs evolved to OSCC during the follow-up period. Three cases had p53 overexpression, while four had a high Ki67/p53 ratio. Statistical significance was reached when samples with p53 overexpression were combined with samples with high Ki67/p53 ratio (Chi square 5.3; p<0.02). The combined immunohistochemical expression of p53 and Ki67 proteins could be a useful and simple molecular marker for early detection of non-dysplastic OLs at risk of developing oral cancer.

Oral leukoplakia and the long‐term risk of upper gastrointestinal cancer deaths in the Linxian dysplasia population

“…21 Previous studies have reported a correlation between p53 and Ki-67 overexpression and OL malignant transformation. [22][23][24] Normal expression of p53 protein is crucial in the process of apoptosis. [25][26][27] Ki-67 is a proliferation marker that is always used to measure the growth fraction of cells in tumors.…”

Alterations in the expression of DNA damage response-related molecules in potentially preneoplastic oral epithelial lesions

“…Immunohistochemical expression of p53, in combination with other molecules (e.g., Ki67 and CA9), has been proposed as marker of MT in oral leukoplakias. 62,63 Furthermore, high p53 expression has been inversely related to clinical response of leukoplakia lesions to chemopreventive beta-carotene and vitamin C supplements. 64 It has been also directly correlated with increased grade of invasive tumor front and tumor depth in OSCC.…”

p53 and ki67 as biomarkers in determining response to chemoprevention for oral leukoplakia

“…Among these p53, ki67, RAR-b, COX 2, EGFR, etc., are known to significantly influence in malignant transformation of oral potentially malignant disorders, particularly 'oral leukoplakia'. We selected p53 as a biomarker as many published studies reported on p53 (6,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28), although most of the studies are retrospective, single centered and consisted of small sample sizes. As shown in Table 2 that lists the summary of p53 and ki67 studies, most of larger-size sample studies have achieved positive outcomes to demonstrate a role p53 in malignant transformation of oral leukoplakia.…”