Association of oral lichen planus with hepatic disorders and hepatocellular carcinoma: systematic review and meta-analysis.

BACKGROUND: Oral lichen planus (OLP) is a prevalent autoimmune chronic inflammatory disease of unknown etiology. The importance of the association between hepatic disease and OLP lies in the fact that many of these disorders (HC, HB, cirrhosis, hepatic steatosis) behave as risk factors for hepatocellular carcinoma. MATERIAL AND METHODS: We searched PubMed, Embase, Web of Science, and Scopus for studies published before January 2022. We evaluated the quality of studies (Joanna Briggs Institute tool). We performed meta-analyses, investigated the heterogeneity between studies, and we also carried out subgroups, meta-regression, and small-study effects analyses. 146 studies (21,187 patients) were included in this study. Our study aims to evaluate current evidence on the prevalence and magnitude of association between hepatic diseases (especially those with risk of malignancy), hepatocellular carcinoma and OLP. RESULTS: Our results suggest that patients with OLP present a significant tendency to the development of hepatitis B (OR=1.62, 95%CI=1.01-2.40, p=0.02), hepatitis C (OR=4.09, 95%CI=2.77-6.03, p<0.001), cirrhosis (OR=5.58, 95%CI=1.83-16.96, p=0.002), hepatic steatosis (OR=5.71, 95%CI=0.97-33.60, p=0.05) and hepatocellular carcinoma (OR=3.10,95%CI=1.14-8.43, p=0.03). CONCLUSIONS: Patients with OLP should be investigated to rule out the presence of hepatic disease, which can lead to hepatocellular carcinoma, allowing an early diagnosis that would help to a better approach to liver disease and a notable improvement in prognosis in terms of both progression and severity.

Dysplasia in oral lichen planus: relevance, controversies and challenges. A position paper.

BACKGROUND: Patients with oral lichen planus (OLP) have an increased risk of oral cancer. For this reason, OLP is classified as an oral potentially malignant disorder. However, the precise personal (or individual) risk is unknown. Recent meta-analytical studies have reported that dysplastic OLP may transform to cancer in around 6% of cases, while the rate of transformation is lower (<1.5%) in non-dysplastic cases. The presence of epithelial dysplasia has emerged as the most powerful indicator for assessing cancer risk in oral potentially malignant disorders in routine practice. However, the general acceptance of epithelial dysplasia as an accompanying histologic feature in OLP is subject to great controversy. Many pathologists consider the presence of dysplasia as a criterion to exclude OLP when routinely reporting on this disease. This practice, widespread among oral pathology professionals, has resulted in the underestimation of the potential for malignancy of OLP. MATERIAL AND METHODS: A review of the literature was carried out in order to critically analyze the relevance, controversies and challenges encountered across the diagnosis of epithelial dysplasia in OLP. RESULTS: 12 studies have been published examining dysplastic changes in OLP, reporting figures ranging from 0.54% to 25% of cases with dysplasia in the first diagnostic biopsy. The diagnosis of dysplasia in the OLP poses an additional difficulty due to the fact that the affected oral epithelium per se develops changes related to autoimmune aggression. Among the most frequent histological features of OLP that develops dysplasia are basal cell hyperplasia with basaloid appearance, loss of basal cells polarity, cellular and nuclear pleomorphism and irregular stratification. CONCLUSIONS: Epithelial dysplasia should not be considered an exclusion criterion for OLP; its evaluation requires experienced pathologists in this field.

Significance of cytoplasmic cyclin D1 expression in oral oncogenesis.

OBJECTIVES: To examine cytoplasmic cyclin D1 expression levels in oral carcinogenesis and evaluate their possible oncogenic significance and their clinicopathological and prognostic implications. MATERIALS AND METHODS: Immunohistochemical analysis of 69 oral squamous cell carcinomas (OSCCs) was performed, revealing 23 with cytoplasmic cyclin D1 expression. We analyzed the association of the percentage of cyclin D1-positive cells and the intensity of expression with TNM classification, tumor stage, differentiation degree, cell morphology, and Ki-67 expression. RESULTS: Cytoplasmic cyclin D1 expression was associated with advanced tumor stage, poor differentiation, elevated Ki-67 expression, and the presence of invasive cell morphology, indicators of a poor prognosis. An association was observed between nuclear and cytoplasmic expressions of cyclin D1. CONCLUSIONS: Cytoplasmic expression of cyclin D1 appears to possess functions related to increased cell migration and invasion in OSCC.

An update on the implications of cyclin D1 in oral carcinogenesis.

Cyclin D1 promotes cell cycle progression during G1 phase, a key event in G1-S transition. The protein is encoded by gene CCND1, located in chromosomal band 11q13. Cyclin D1 plays key roles in cell biology, including cell proliferation and growth regulation, mitochondrial activity modulation, DNA repair, and cell migration control. CCND1 gene and its protein cyclin D1 are frequently altered by different molecular mechanisms, including amplification, chromosomal translocations, mutations, and activation of the pathways involved in cyclin D1 expression, alterations which appear to be essential in the development of human cancers, including oral carcinoma. This is the first published review of the specific features of cyclin D1 overexpression in oral oncogenesis. Starting with the physiological regulation of cyclin D1, there is an evaluation of its functions, overexpression mechanisms, and the implications of the oncogenic activation of CCND1/cyclin D1 in oral squamous cell carcinoma. The potential diagnostic and prognostic value of cyclin D1 is reviewed. The influence of CCND1/cyclin D1 on tumor size and clinical stage is reported, and an update is provided on the utilization of cyclin D1 as therapeutic target and on the combination of cyclin D1 inhibitors with cytotoxic agents. Future research lines in this field are also proposed.

Asymmetrical proliferative pattern loss linked to cyclin D1 overexpression during malignant transformation of the lip epithelium.

BACKGROUND: There is inadequate knowledge on the involvement of oncogenic mechanisms linked to the cyclin (CCND1) gene in lip squamous cell carcinoma (LSCC). OBJECTIVE: The aim of this study was to analyse the implication of cyclin D1 in the malignant transformation of lip lesions. METHODS: We immunohistochemically studied 45 actinic cheilitis cases (15 mild dysplasia, 15 moderate dysplasia, 15 severe dysplasia/carcinoma in situ), 30 LSCC cases with adjacent non-tumour epithelium and 15 normal oral epithelium samples for detection of cyclin D1, ß-catenin and Ki-67. RESULTS: Cyclin D1 and Ki-67 expressions were significantly increased in the basal layer of premalignant epithelia and peripheral layers of tumour nests vs. CONTROLS: Premalignant epithelia had lost their asymmetrical proliferative pattern. CONCLUSION: Lip carcinogenesis was associated with loss of the asymmetrical proliferative pattern, a preventive mechanism against lip oncogenesis, and with cyclin D1 overexpression.