Immunohistochemistry profile of p75 neurotrophin receptor in oral epithelial dysplasia and oral squamous cell carcinoma induced by 4-nitroquinoline 1-oxide in rats.

Highlights • p75 neurotrophin receptor (p75NTR) is a marker for cancer stem cells in head and neck cancers. • p75NTR expression was not addressed in 4-nitroquinoline 1-oxide (4-NQO)-induced oral carcinogenesis in rats. • p75NTR expression in 4-NQO-induced oral lesions is similar to that observed in head and neck cancers. • p75NTR may be useful to predict loss of cell differentiation during oral carcinogenesis. Abstract Objective The 4-nitroquinoline 1-oxide (4-NQO) model for carcinogenesis has been used to investigate cancer stem cells (CSC), but no study has addressed the role of the p75 neurotrophin receptor (p75NTR) in 4-NQO-induced oral dysplasia and oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate the immunohistochemistry profile of the p75NTR during 4-NQO-induced oral carcinogenesis in rats and to verify whether this profile has an association with proliferating cell nuclear antigen (PCNA) immunolabeling. Design For 28 weeks, rats were exposed to 4-NQO, which was diluted in the drinking water. After 3, 5, 7, 16, and 28 weeks, the animals were euthanized and their tongues were histologically analyzed using p75NTR and PCNA immunolabeling. Results In animals without 4-NQO exposure, the p75NTR and PCNA were expressed only in the basal epithelial layer and in a clustered manner. The oral epithelium showed dysplasia and a significant increase in the number of p75NTR- and PCNA-positive cells, which were localized mainly in the basal and suprabasal epithelial layers during weeks 5–16 of 4-NQO exposure. When the epithelium invaded the lamina propria and well-differentiated OSCC began, the p75NTR-positive cell frequency drastically decreased in epithelial cords and nests, showing a negative correlation with PCNA expression. p75NTR immunolabeling during 4-NQO-induced carcinogenesis was similar to that described for human head and neck dysplasia and neoplasia. Conclusions p75NTR immunolabeling observed in 4-NQO-induced oral dysplastic and OSCC lesions were related to the early phases of oral carcinogenesis and may help predict cell dysplasia and malignant transformation. [ABSTRACT FROM AUTHOR]