José Antonio Gil-Montoya

Oral lichen planus: controversies surrounding malignant transformation

Studies of the malignant potential of oral lichen planus (OLP) have been hampered by inconsistencies in the diagnostic criteria used for OLP, the criteria adopted to identify a true case of malignant transformation in OLP, the risk factors for malignant transformation and the optimum management of patients to ensure the early diagnosis of transformation. Consensus remains elusive, and leading workers in this field have recently published conflicting reports on the malignant potential of OLP and on the important question of the advisability of excluding patients with epithelial dysplasia or a tobacco habit from studies on this issue. The present review outlines these debates and proposes a possible a molecular basis for the malignant transformation in this disease.

Oral health in the elderly patient and its impact on general well-being: a nonsystematic review.

Data on the oral health of the elderly depict a worrying situation, with an elevated prevalence of caries and moderate periodontal disease, frequent edentulism, and numerous cases of dry mouth and oral cancer. There is wide evidence that periodontitis is a risk factor for certain systemic diseases, and impaired oral health has been associated with mastication and nutritional problems, especially among the elderly, with highly negative effects on their quality of life. In this nonsystematic review, the authors discuss the importance of evaluating the oral health of the geriatric population in a comprehensive manner, beyond simple clinical assessments.

Evaluation of the clinical efficacy of a mouthwash and oral gel containing the antimicrobial proteins lactoperoxidase, lysozyme and lactoferrin in elderly patients with dry mouth – a pilot study

OBJECTIVES To evaluate the clinical efficacy of a mouthwash and oral gel containing the antimicrobial proteins lactoperoxidase, lactoferrin and lysozyme, in a sample of elderly individuals with dry mouth. MATERIAL AND METHODS Twenty elderly institutionalised subjects with dry mouth and with a certain degree of independence for daily life activities were included in this pilot study. A randomised, double blind and cross-over design was used. The study variables comprised subjective dry mouth sensation, the severity of discomfort assessed by means of a visual analogical scale (VAS), the Oral Health Impact Profile (OHIP), the presence of signs and symptoms of dry mouth, sialometry and Candida albicans culture. All the variables were recorded before and after each of the two periods of the study. RESULTS The 20 selected subjects we made up of 16 women and four men, with a mean age of 81.3 years. Improvement was observed on analysing the data between the first and second intervention period in terms of the OHIP values, the presence of dry mouth, and the need to drink fluids to swallow. However, the improvement in certain variables before and after treatment did not take a positive course in all cases, and some subjects even improved with placebo. CONCLUSIONS The evaluated mouthwash and oral gel improved some subjective and clinical aspects in elderly individuals with dry mouth, though a placebo effect cannot be entirely discarded.

Analysis of Ki-67 expression in oral squamous cell carcinoma: Why Ki-67 is not a prognostic indicator

OBJECTIVES To analyze the prognostic value of Ki-67 in oral cancer and its relationship with Ki-67 expression in precancerous epithelium. MATERIAL AND METHODS We studied 79 tumors from 65 patients. Immunohistochemistry study with Mib-1 monoclonal antibody was used to detect Ki-67 expression in tumor tissue and adjacent non-tumor tissue. The influence of different variables on survival was studied with univariate and multivariate analyses. RESULTS Ki-67 expression was significantly higher in well-differentiated versus poorly-differentiated carcinomas. The survival time of these patients was affected by the clinical presentation, T, N, stage, and surgical treatment. Ki-67 expression had no impact on survival. An association was found between the parabasal expression of Ki-67 in adjacent non-tumor epithelium and Ki-67 expression in the tumor. CONCLUSIONS Ki-67 lacks prognostic value, probably because it is a marker of the total fraction of proliferating cells, corresponding not only to cells in constant proliferation but also to proliferating cells destined for terminal differentiation.

Cell proliferation associated with actions of the substance P/NK-1 receptor complex in keratocystic odontogenic tumours

The expression of substance P (SP) and its NK-1 receptor (NK-1R) in keratocystic odontogenic tumours (KOTs) was studied to determine whether the intrinsic growth potential of these lesions is related to a cell proliferation stimulus mediated by the SP/NK-1R complex. A total of 65 tissue samples of solitary non-recurrent KOTs, solitary recurrent KOTs, KOTs associated with nevoid basal cell carcinoma syndrome (NBCCS) and KOTs with chondroid wall were studied by immunohistochemistry, using anti-SP, anti-NK-1R and anti-Ki-67 monoclonal antibodies. Expression of these markers was analysed in infiltrating lymphocytes, in fibrous capsule, and in membrane, cytoplasm and nucleus of epithelial cells. SP expression in infiltrating lymphocytes was significantly associated with SP in fibrous capsule and epithelial cells. KOTs associated with NBCCS showed a significantly higher SP expression in all tissues and cell compartments compared with other KOT types. Finally, SP expression in epithelial cells was associated with positive Ki-67 expression in dysplastic epithelium. This first published report on SP and NK-1R expressions in KOTs demonstrates that actions of the SP/NK-1R complex may constitute a mechanism to stimulate epithelial cell proliferation in KOT. This pathway may be of special relevance in the multiple KOTs associated with NBCCS.

β-catenin in oral cancer: an update on current knowledge.

β-Catenin is a multiple function protein. These functions derive from its interactions with other cell proteins, both on the cell membrane, in the cytoplasm and in the nucleus. β-Catenin forms a complex with the adhesion molecule E-cadherin, promoting cell-cell adhesion and thereby preventing the cell dissociation that is required for cancer invasion and progression mechanisms. There is also a dynamic pool of cytoplasmic β-catenin that serves as connection between the extracellular microenvironment and the nucleus. Cytoplasmic β-catenin acts as a transcription factor for the nucleus in the canonical Wnt pathway, activating the transcription of various genes. Structural or functional alterations of β-catenin can promote cancer progression. This review addresses the current knowledge on the implications of β-catenin in the development of oral cancer.

Ki‐67 expression in non‐tumour epithelium adjacent to oral cancer as risk marker for multiple oral tumours

OBJECTIVE The aim of this study was to determine whether the differential assessment of epithelial proliferation is useful to diagnose premalignant fields and assess the risk of multiple tumours. MATERIAL AND METHODS We analysed 83 oral carcinomas with associated non-tumour epithelium classified as distant or close according to its distance (> or <1 cm) from the invasion point, and as squamous hyperplasia, mild, moderate, severe dysplasia or carcinoma in situ. Twenty-five healthy oral mucosa samples were used as controls. An immunohistochemical technique was applied using Mib-1. Ki-67 in premalignant epithelium was assessed in basal layer, parabasal layer, medium and upper third. RESULTS Parabasal expression was significantly higher or showed a tendency to be higher in close and distant epithelia with any histological grade than in the controls. Parabasal Ki-67 significantly differed between distant epithelia associated with multiple vs single tumours (P < 0.001) and between distant epithelia associated with multiple tumours vs controls (P < 0.001). This difference was not observed between distant epithelia associated with single tumours and controls (P = 0.175). The cut-off point that differentiated epithelia associated with multiple tumours was >50% of Ki-67 + parabasal cells in distant epithelia, which yielded 0.88 sensitivity and 0.79 specificity. CONCLUSIONS The concept of a precancerous field may be linked to an increase in the proliferative activity of parabasal cells.

Is Periodontitis a Risk Factor for Cognitive Impairment and Dementia? A Case‐Control Study

BACKGROUND Dementia is a multi-etiologic syndrome characterized by multiple cognitive deficits but not always by the presence of cognitive impairment. Cognitive impairment is associated with multiple non-modifiable risk factors but few modifiable factors. Epidemiologic studies have shown an association between periodontitis, a potentially modifiable risk factor, and cognitive impairment. The objective of this study is to determine whether clinical periodontitis is associated with the diagnosis of cognitive impairment/dementia after controlling for known risk factors, including age, sex, and education level. METHODS A case-control study was conducted in Granada, Spain, in two groups of dentate individuals aged >50 years: 1) cases with a firm diagnosis of mild cognitive impairment or dementia of any type or severity and 2) controls with no subjective memory loss complaints and a score >30 in the Phototest cognitive test (screening test for cognitive impairment). Periodontitis was evaluated by measuring tooth loss, plaque and bleeding indexes, probing depths, and clinical attachment loss (AL). RESULTS The study included 409 dentate adults, 180 with cognitive impairment and 229 without. A moderate and statistically significant association was observed between AL and cognitive impairment after controlling for age, sex, education level, oral hygiene habits, and hyperlipidemia (P = 0.049). No significant association was found between tooth loss and cognitive impairment. CONCLUSION Periodontitis appears to be associated with cognitive impairment after controlling for confounders such as age, sex, and education level.

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.

No differences in caspase-3 and Bax expression in atrophic-erosive vs. reticular oral lichen planus

Background  Caspase‐3 (CPP32) and Bax expression levels in oral lichen planus (OLP) lesions are considered reliable markers of apoptosis. The malignant transformation of OLP remains a very controversial matter. The objective of this study was to compare histological and apoptotic phenomena between atrophic‐erosive and reticular forms of OLP.