Association between p62 expression and clinicopathological characteristics in oral leukoplakia

Abstract

Objective Oral leukoplakia is keratinized lesions in the buccal mucosa, tongue, and gingiva. It is the most common oral precancerous lesion; oxidative stresses and irrelevant autophagy have been reported to be the cause of oncogenesis. p62, a cytoplasmic protein induced by oxidative stress, is an adaptor protein involved in the formation of protein aggregates and induction and inhibition of autophagy. The inhibition of autophagy induces p62 overexpression and promotes oncogenesis via the oncogenic signaling pathway. The aim of the present study was to elucidate the involvement of intracellular expression of p62 in oral leukoplakia and to address its potential clinical implementation as a biomarker to predict malignant transformation. Material and Methods Fifty samples from subjects with confirmed oral leukoplakia were evaluated by immunohistochemical staining for the expression of p62, 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), Ki67, and p53. Univariate and multivariate logistic regression analyses were performed to evaluate the association between p62, 8‐OHdG, Ki67, and p53 and clinical characteristics, including epithelial dysplasia. Results Significant associations were observed between p62 expression in the nucleus, p62 aggregation, and epithelial dysplasia (adjusted odds ratio [OR] = 5.75; 95% confidence interval [CI]: [1.28, 26.2]; .024 and OR = 6.16; 95% CI: [1.01, 37.4]; .048, respectively). The expression of p62 in the cytoplasm and the levels of 8‐OHdG, Ki67, and p53 were not significantly associated with epithelial dysplasia. A significant relationship was found between p62 expression in the nucleus and p53 expression (OR = 3.94; 95% CI: [1.14, 13.6]; .031). Conclusions The results suggested that p62 expression in the nucleus and p62 aggregation can be potential markers to predict the malignant transformation of oral leukoplakia.

p62 Is a Potential Biomarker for Risk of Malignant Transformation of Oral Potentially Malignant Disorders (OPMDs)

“…Staining for p62 was evaluated separately for nucleus, cytoplasm, and aggregation. In accordance with our previous research, we defined a cell positive for p62 aggregation staining as one with at least one dot of accumulation in the cytoplasm in 20× and 40× field of view [ 18 ]. Representative images of p62 aggregation are shown in Figure 2 .…”

“…We previously reported that the expression of autophagy-related markers, including p62, at the resection margins of OSCC was associated with tumor recurrence [ 17 ]. We also found that p62 expression in the nucleus and p62 aggregation in oral leukoplakia were related to the presence or absence of epithelial dysplasia [ 18 ]. This suggests that p62, an adaptor of selective autophagy, may be useful as a marker for assessing the risk of recurrence at the resection margin of OSCC as well as the risk of malignant transformation in precancerous lesions.…”

“…Yoshida et al reported the expression of p62 in oral leukoplakia; however, to the best of our knowledge, there are no studies on the expression of p62 in OPMDs [ 18 ]. Lin et al reported that p62 showed a change in subcellular localization between oral mucosa and OSCC, suggesting that the subcellular localization of p62 changes in association with malignant transformation [ 19 ].…”

La expresión de 8-hidroxi 2’-desoxiguanosina en el cáncer

“…La expresión de 8-hidroxi 2'-desoxiguanosina en el cáncer Tequio 5 (15), 2022: [31][32][33][34][35][36][37][38][39][40] ISSN: 2594-0546 TEQUIO, mayo-agosto 2022, vol. 5, no.…”

“…En adición a lo anterior, ahora se sabe que los niveles salivales del 8-OHdG están aumentados en los pacientes con cáncer oral de células escamosas y otros desórdenes orales potencialmente malignos (Bahar, Feinmesser, Shpitzer, Popovtzer y Nagler, 2007); (Nandakumar, Nataraj, James, Krishnan y Mahesh, 2020).Por el contrario, en las lesiones precancerosas de pacientes con leucoplasia oral, la expresión del 8-OHdG se mantiene sin cambios(Yoshida et al, 2019), lo cual sugiere que la sobreexpresión de esta molécula pudiera estar restringida únicamente a las células cancerígenas de la cavidad oral. No obstante, también se ha informado que la expresión del 8-OHdG en pacientes con carcinoma de células escamosas no incrementa (Yoshifuku, A., Fujii, K., & Kanekura, T. 2018), lo cual está en contraposición a lo descrito líneas arriba en este párrafo.Con relación a otros tipos de cáncer, se tiene la evidencia de que la expresión del 8-OHdG aumenta en pacientes con adenocarcinoma de esófago y hepatocarcinogénesis(Chuma et al, 2008); (Räsänen, Sihvo, Ahotupa, Färkkilä y Salo, 2007).…”