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Diagnosis of Oral Hairy Leukoplakia: The Importance of EBV In Situ Hybridization.

ABSTRACT: Oral hairy leukoplakia (OHL) is caused by the Epstein-Barr virus (EBV), which has been related to HIV infection. In situ hybridization (ISH) is the gold-standard diagnosis of OHL, but some authors believe in the possibility of performing the diagnosis based on clinical basis. The aim of this study is diagnose incipient lesions of OHL by EBV ISH of HIV-infected patients and the possible correlations with clinical characteristics of the patients. Ninety-four patients were examined and those presenting with clinical lesions compatible to OHL were submitted to biopsy prior to EBV ISH. Twenty-eight patients had lesions clinically compatible to the diagnosis of OHL, but only 20 lesions were confirmed by EBV ISH. The patients with OHL had a mean age of 41.9 years and were HIV-infected for 11.2 years, on average, including CD4 count of 504.7 cells/mm3 and log10 viral load = 1.1. Among the quantitative variables, there was a statistically significant correlation with age only (P = 0.030). In conclusion, the presence of OHL in patients with HIV/AIDS results in changes in the epidemiological characteristics of the disease, and this fact allied with subtle clinical-morphological features makes clinical diagnosis very difficult. Therefore, EBV ISH is important for a definitive diagnosis of OHL.

SUBMITTER: Martins LL

PROVIDER: S-EPMC5536144 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:The programmed cell death ligand 1/programmed cell death receptor 1 (PD-L1/PD-1) Immune Checkpoint is an important modulator of the immune response. Overexpression of the receptor and its ligands is involved in immunosuppression and the failure of an immune response against tumor cells. PD-1/PD-L1 overexpression in oral squamous cell carcinoma (OSCC) compared to healthy oral mucosa (NOM) has already been demonstrated. However, little is known about its expression in oral precancerous lesions like oral leukoplakia (OLP). The aim of the study was to investigate whether an increased expression of PD-1/PD-L1 already exists in OLP and whether it is associated with malignant transformation. PD-1 and PD-L1 expression was immunohistologically analyzed separately in the epithelium (E) and the subepithelium (S) of OLP that had undergone malignant transformation within 5 years (T-OLP), in OLP without malignant transformation (N-OLP), in corresponding OSCC and in NOM. Additionally, RT-qPCR analysis for PD-L1 expression was done in the entire tissues. Additionally, the association between overexpression and malignant transformation, dysplasia and inflammation were examined. Compared to N-OLP, there were increased levels of PD-1 protein in the epithelial and subepithelial layers of T-OLP (pE = 0.001; pS = 0.005). There was no significant difference in PD-L1 mRNA expression between T-OLP and N-OLP (p = 0.128), but the fold-change increase between these groups was significant (Relative Quantification (RQ) = 3.1). In contrast to N-OLP, the PD-L1 protein levels were significantly increased in the epithelial layers of T-OLP (p = 0.007), but not in its subepithelial layers (p = 0.25). Importantly, increased PD-L1 levels were significantly associated to malignant transformation within 5 years. Increased levels of PD-1 and PD-L1 are related to malignant transformation in OLP and may represent a promising prognostic indicator to determine the risk of malignant progression of OLP. Increased PD-L1 levels might establish an immunosuppressive microenvironment, which could favor immune escape and thereby contribute to malignant transformation. Hence, checkpoint inhibitors could counteract tumor development in OLP and may serve as efficient therapeutic strategy in patients with high-risk precancerous lesions.

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Diagnosis of Oral Hairy Leukoplakia: The Importance of EBV In Situ Hybridization.

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