Expression of the cell cycle regulation proteins p53 and p21WAF1 in different types of non-dysplastic leukoplakias

Abstract

ObjectivesThe aim of this study was to analyze the immunolabeling of two cell cycle protein regulators, p53 and p21WAF1, in non-dysplastic leukoplakias with different epithelial alterations: acanthosis, hyperkeratosis and acanthosis combined with hyperkeratosis, and compare them with dysplastic leukoplakias.Material and MethodsThis was a prospective cohort study involving 36 patients with oral homogeneous leukoplakias. Excisional biopsies were performed and the patients remain under clinical follow-up. The leukoplakias were divided into four groups: 6 acanthosis, 9 hyperkeratosis, 10 acanthosis combined with hyperkeratosis, and 11 epithelial dysplasias. Paraffin-embebeded sections were immunostained for p53 and p21WAF1. Five hundred cells from the basal layer and 500 from the parabasal layer were counted to determine the percentage of positive cells. A qualitative analysis was also carried out to determine the presence or absence of immunohistochemical staining in the intermediate and superficial layers. Groups were compared with ANOVA (p<0.05). Pearson's correlation coefficient was used to test for associations between the two markers, p53 and p21WAF1.ResultsNo leukoplakia recurred and no malignant transformation was observed whitin a follow-up period of 3-6 years. The mean percentage of p53 staining in the basal and parabasal layers was similar in all groups. p21WAF1 staining differed between layers was as follows: in the basal, only 3 to 4% of cells were stained, while in the parabasal, between 16 and 28% of the epithelial cells were stained in the four different studied groups with no statistically significant difference (p>0.05).ConclusionsOur findings failed to differentiate the non-dysplastic lesions by means of p53 and p21WAF1 immunostaining, notwithstanding similar profiles between non-dysplastic and dysplastic leukoplakias were observed.

Oral keratosis of unknown significance shares genomic overlap with oral dysplasia

“…Recent work has shown that high‐risk TP53 mutations are progressively more common from hyperplasia to dysplasia to progressive OCSCC (William et al, ). It has also been demonstrated that p53 and other cell cycle regulator expression levels appear similar in non‐dysplastic and dysplastic lesions when histologically categorizing oral leukoplakia cases (Visioli, Lauxen, Sant'ana Filho, & Rados, ), providing further support to the hypothesis that molecular aberrations among oral precancerous lesions may occur before dysplasia is histopathologically diagnosed, as in the case of KUS.…”

Inhomogeneity of stiffness and density of the extracellular matrix within the leukoplakia of human oral mucosa as potential physicochemical factors leading to carcinogenesis

“…Notably, p53 expression was also significant in margins and was especially prominent in 50% of the samples. The above findings may indicate inhibition of the apoptotic process and abnormal cell cycle regulation in such cells [ 66 , 68 ]. Nuclear expression of p53 protein was significantly stronger in squamous cell hyperplasia with dysplasia and squamous cell carcinoma samples comparing to margins and healthy oral mucosa.…”

World Workshop on Oral Medicine VII: Prognostic biomarkers in oral leukoplakia: A systematic review of longitudinal studies

“…Biomarkers reported in these studies (Table ) included inflammatory or oxidative markers (Chang et al., ; Massarelli et al., ; Rai, Kaur, Jacobs, & Singh, ), growth factors (Beenken et al., , ; Uehara, Ikeda, Nonaka, & Asahina, ; Wan, Meyskens, Armstrong, Taylor, & Kennedy, ), cell signaling biomarkers (Saintigny et al., , , ; Sakata et al., ), genetic and cellular regulatory factors (Lee et al., ; Mao et al., ; Nagao et al., ; Tanic, Tanic, Milasin, Vukadinovic, & Dimitrijevic, ; Visioli, Lauxen, Sant'ana Filho, & Rados, ), ion channels (Fernandez‐Valle, Rodrigo, Garcia‐Pedrero, et al., ; Fernandez‐Valle, Rodrigo, Rodriguez‐Santamarta, et al., ), sustained angiogenesis factors (Kawaguchi et al., ; Lin et al., ; Nayak et al., ; Saintigny et al., ; Yang et al., ), and epigenetic biomarkers (Foy et al., ; Xiao et al., ; Yang et al., ). Studies tended to include small sample sizes, under‐reported or variably reported histopathological data, did not address potential confounding, reported limited/variable follow‐up data, or lacked a control group.…”