Reticular and erosive oral lichen planus have a distinct metabolomic profile: A preliminary study using gas chromatography-mass spectrometry.

BACKGROUND: Oral Lichen Planus is a chronic inflammatory disorder that affects the oral mucosa, with the reticular and erosive forms representing the primary clinical variants of the disease. Previous studies have shown that metabolic alterations may well be involved in the pathogenesis of the disease; however, the molecular mechanisms related to the clinicopathological differences between erosive and reticular forms remain unknown. METHODS: A comparative metabolomic analysis was performed on formalin-fixed and paraffin-embedded tissue samples of erosive (n = 6) and reticular (n = 10) oral lichen planus using gas chromatography-mass spectrometry. RESULTS: The metabolomic analysis showed a distinct profile between the two clinical variants. Five metabolites (cyclohexanamine, glycine, mannitol/sorbitol, methyl palmitate and trehalose) were significantly diminished in erosive oral lichen planus as compared to the reticular form. CONCLUSIONS: Reticular and erosive forms of oral lichen planus have a distinct metabolic profile. However, further studies using a large number of fresh tissue samples are necessary to confirm this data.

Oral lichen planus - Differential diagnoses, serum autoantibodies, hematinic deficiencies, and management.

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease that occurs more frequently in middle-aged and elderly female patients. Previous studies indicate that OLP is a T-cell dysfunction-induced localized autoimmune disease. Clinically, six types of OLP, namely reticular, papular, plaque-like, atrophic/erosive, ulcerative, and bullous types, can be identified. OLP more commonly affects buccal mucosa, tongue, and gingiva. It always has a bilateral and symmetric distribution of the oral lesions. Plaque-like and atrophic/erosive OLP may be misdiagnosed as oral leukoplakia and oral erythroleukoplakia, respectively. Our previous study found serum autoantibodies in 195 (60.9%) of the 320 OLP patients. Specific serum anti-nuclear, anti-smooth muscle, anti-mitochondrial, gastric parietal cell, thyroglobulin, and thyroid microsomal autoantibodies are present in 28.1%, 8.4%, 1.6%, 26.3%, 21.3%, and 24.4% of 320 OLP patients, respectively. Furthermore, we also discovered that 21.9%, 13.6%, 7.1%, 0.3%, and 14.8% of 352 OLP patients have hemoglobin, iron, vitamin B12, and folic acid deficiencies, and abnormally high serum homocysteine level, respectively. Therefore, it is very important to examine the serum autoantibody, hematinic and homocysteine levels in OLP patients before starting the treatments for OLP patients. Because OLP is an immunologically-mediated disease, corticosteroids are the drugs of choice for treatment of OLP.

Histopathological characterization of the oral lichenoid disease subtypes and the relation with the clinical data.

BACKGROUND: The aim of the study was to analyze the histopathological characteristics of samples with a diagnosis of oral lichenoid disease (OLD) and their link with the location and the type of clinical lesion, and the clinicopathological subtypes. MATERIAL AND METHODS: Retrospective study on 85 consecutive patients diagnosed with OLD (58 women and 27 men, mean age of 57.7 years). Clinical and histopathological characterization of each case (modified WHO criteria). Collection of the clinical and histopathological data of the lesions. Descriptive and comparative statistical analysis of the results. RESULTS: The 78.8% of the cases were considered clinically typical while the 21.2% were considered compatible. Histologically, 52.9% were classified as typical and 47.1% as compatible. Biopsies from "plaque-like" lesions presented hyperkeratosis (p>0.001) and epithelial dysplasia (p=0.06) more frequently. Furthermore, acute inflammation was more evident in erosive-ulcerative lesions (p=0.001). Differences regarding the location of the biopsy were statistically non-significant. However, 42.9% of the tongue biopsies showed epithelial dysplasia. CONCLUSIONS: The histopathological aspect of this disorder is not specific and does not allow us to differentiate between the main subtypes. Therefore, the main reasons to perform a biopsy in this disorder are to define the differential diagnosis and to rule out epithelial dysplasia or a carcinoma. The final histopathological result may be subject to the type of lesion that is biopsied.

[Analysis of type C behavior in patients with oral lichen planus].

OBJECTIVE: To assess type C behavior in patients with oral lichen planus (OLP) in order to provide basis for clinical prevention, treatment and psychological intervention of OLP. METHODS: Type C behavior scale was used on 85 OLP patients and 85 control patients, who were in accordance with the inclusion criteria, in order to investigate their type C behavior. The scale included 9 items: anxiety, depression, anger, anger toward inside (anger-in), anger toward outside (anger-out), reasoning, domination, optimism, and social support. Scores of the 9 items between OLP patients and control group were calculated under the instruction of the scale and were statistically analyzed, and OLP group was further stratified statistically by sex, reticulate-erosive-ulcerative (REU) pathological type and course of diseases, and the scores of each group were analyzed and compared. RESULTS: Among the 85 OLP patients, there were more females, more non-erosive lesion type, and the most common site for OLP was the buccal mucosa. The scores of the type-C behavior questionnaire for anxiety, depression, anger and optimism were respectively 43.01±7.47, 44.02±7.61, 21.56±5.26, 22.15±4.00 among the OLP patients and were 37.94±8.70, 39.58±7.35, 18.12±5.39, 24.05±3.23 among control group, with significant differences(P<0.05 for all) between the two groups. The female OLP patients had higher anxiety, depression, anger scores (43.21±6.97, 44.29±7.54, 21.64±5.09) and lower reasoning, domination, optimism scores (39.12±5.66, 16.29±3.95, 22.05±4.12) with significant differences (P<0.05 for all) compared with those of the female controls. The scores between male patients and male controls showed no significant difference. The patients with erosive lesions had higher anger score (22.94±5.26) than that of the patients without erosive lesions(20.60±5.03), with a significant difference(P<0.05). With the development of the disease, the tendency of anxiety and depression of the patients were more obvious, while optimism scores remained declining. The patients suffering more than 3 years of OLP had higher anger-toward-outside scores (17.36±3.35) than the patients suffering less than 3 years of OLP (15.19±3.99), with a significant difference (P<0.05). CONCLUSION: OLP patients showed an obvious type C behavior characteristic, especially in anxiety, depression, anger and low optimism. This research provides the C behavior characteristic of OLP for further psychological consultation or intervention during OLP treatment.

The impact of structured plaque control for patients with gingival manifestations of oral lichen planus: a randomized controlled study.

AIM: To evaluate the impact of a structured plaque control intervention on clinical and patient-centred outcomes for patients with gingival manifestations of oral lichen planus. MATERIALS AND METHODS: Eighty-two patients were recruited into a 20-week randomized controlled trial. The intervention was structured plaque control comprising powered tooth brushing and inter-dental cleaning advice. Control subjects continued with their normal dental plaque control regimen. The primary outcome measure was the oral health impact profile (OHIP) with secondary outcomes of pain, plaque index, mucosal disease score and cost-effectiveness. RESULTS: Overall, the intervention patients showed statistically significant improvements in OHIP sum ordinal and OHIP dichotomous scores compared with control. There were improvements in the functional limitation, psychological discomfort and physical disability domains at 4- and 20-weeks and in the psychological disability domain at 20-weeks. The intervention was successful in reducing plaque compared to control (p < 0.001) and improvements were observed using the mucosal disease indices at the 4- and 20-week follow-ups (p < 0.001). CONCLUSION: A structured plaque control intervention was effective in improving the oral health-related quality of life and clinically observed gingival lesions. This study provides evidence to include intensive plaque control within patients' initial and on-going management.

Disease scoring systems for oral lichen planus; a critical appraisal.

The aim of the present study has been to critically review 22 disease scoring systems (DSSs) on oral lichen planus (OLP) that have been reported in the literature during the past decades. Although the presently available DSSs may all have some merit, particularly for research purposes, the diversity of both the objective and subjective parameters used in these systems and the lack of acceptance of one of these systems for uniform use, there is a need for an international, authorized consensus meeting on this subject. Because of the natural course of OLP characterized by remissions and exacerbations and also due to the varying distribution pattern and the varying clinical types, e.g. reticular and erosive, the relevance of a DSS based on morphologic parameters is somewhat questionable. Instead, one may consider to only look for a quality of life scoring system adapted for use in OLP patients.

Interleukin-6 and neopterin levels in the serum and saliva of patients with Lichen planus and oral Lichen planus.

BACKGROUND: Lichen planus together with its oral variant is a chronic, inflammatory disease of the skin and the mucosa of unclear aetiology and with an unpredictable course that still poses a major problem in terms of diagnosis and treatment. The objective of this study was to assess the concentrations of interleukin-6 (IL-6) and neopterin in saliva and serum of patients with lichen planus (including reticular and erosive form of oral lichen planus) and to compare them with the concentrations observed in healthy controls. METHODS: The study material comprised serum and saliva samples from 56 patients diagnosed with lichen planus and 56 healthy volunteers. The ELISA test was used to measure concentrations of IL-6 and neopterin in the serum and saliva of the study participants. RESULTS: The concentrations of IL-6 in saliva and serum of patients with lichen planus were significantly higher than in controls (P = 0.0002; P < 0.0001). The difference remains significant after adjustment for gingivitis and age. Patients with atrophic-erosive oral lichen planus had significantly higher IL-6 concentrations in their saliva compared to patients with reticular form of disease (P = 0.01). The concentrations of neopterin were significantly higher in the serum but not in saliva of lichen planus patients vs. controls (P <0.0001). CONCLUSIONS: Serum levels of proinflammatory cytokines IL-6 and neopterin are increased in lichen planus as well as the salivary concentrations of IL-6. The differences observed in IL-6 levels in patients with erosive-atrophic forms of oral lichen planus may indicate a substantial role played by the cytokine in the disease.

Epidermal growth factor receptor expression in different subtypes of oral lichenoid disease.

UNLABELLED: The oral lichenoid disease (OLD) includes different chronic inflammatory processes such as oral lichen planus (OLP) and oral lichenoid lesions (OLL), both entities with controversial diagnosis and malignant potential. Epidermal growth factor receptor (EFGR) is an important oral carcinogenesis biomarker and overexpressed in several oral potentially malignant disorders. OBJECTIVES: To analyze the EGFR expression in the OLD to find differences between OLP and OLL, and to correlate it with the main clinical and pathological features. MATERIAL AND METHODS: Forty-four OLD cases were studied and classified according to their clinical (Group C1: only papular lesions / Group C2: papular and other lesions) and histopathological features (Group HT: OLP-typical / Group HC: OLP-compatible) based in previous published criteria. Standard immunohistochemical identification of EGFR protein was performed. Comparative and descriptive statistical analyses were performed. RESULTS: Thirty-five cases (79.5%) showed EGFR overexpression without significant differences between clinical and histopathological groups (p<0.05). Histological groups showed significant differences in the EGFR expression pattern (p=0.016). Conlusions: All OLD samples showed high EGFR expression. The type of clinical lesion was not related with EGFR expression; however, there are differences in the EGFR expression pattern between histological groups that may be related with a different biological profile and malignant risk.

A comparative immunohistochemical and immunophenotypical study on lymphocytes expression in patients affected by oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is an immune-mediated mucocutaneous disease of uncertain aetiology. OLP has many manifestations: reticular, erosive, atrophic, plaque like, papular, bullous, with unique etiopathogenetic working. The purpose of this study is to find a link between different clinical types of lichen and the alterations of lymphocytes on peripheral blood and oral mucosa. MATERIALS AND METHODS: A total of 21 patients were enrolled in this study. The mean age of patients was 53.82 years, between 31 and 78 years. OLP Diagnosis was afterwards confirmed by histopathology. Selected patients underwent to clinical evaluation, lesion characterization, incisional biopsy, samples histological analysis, peripheral blood collection. Blood specimens were submitted to cell count determination with differential, characterization of populations and circulating lymphocyte subpopulations using monoclonal antibodies in flow cytometry. Referring to the clinical presentation of lesions, patients were divided in two groups: red lesions (RL) and white lesions (WL) and compared with an age-matched control group. RESULTS: The results of the immunophenotypic study showed correlation between WL and the expression of CD19 lymphocytes (r = 0.693, P = 0.0005). The results of immunohistochemical study performed on histological specimens showed a significant correlation between RL group and expression of all lymphocyte tested (CD3 r = 0.722 P = 0.0002, CD4 r = 0.579 P = 0.0060, CD56 r = 0.513 P = 0.0173, CD8 r = 0.548 P = 0.0102). CONCLUSIONS: We assume there is the responsibility of the expression of lymphocytes, not only type but also as quantity, in determining RL or WL manifestation of OLP. Circulating lymphocytes may have a role, too.

Analysis of the expression of heat-shock protein 27 in patients with oral lichen planus.

OBJECTIVE: Heat-shock protein 27 (hsp27) has been implicated in several biological events. In this experimental study, we aimed at analysing, for the first time, the expression of hsp27 in the diverse stages of oral lichen planus (OLP) lesions. MATERIALS AND METHODS: Thirty-six biopsy specimens of patients with OLP and 10 of healthy patients were selected. OLP specimens were divided into three groups: G1 - moderate or mildly active OLP; G2 - active or moderately active atrophic OLP; G3 - mild or inactive atrophic OLP. Hsp27 expression was analysed by immunohistochemistry (staining intensity and percentage of stained cells), and results of staining were compared between the different groups. Gender, age and anatomical location were also studied. RESULTS: In the basal layer, an increase of hsp27 expression in both G2 and G3 was observed when compared to G1 and control group. In contrast, a decrease of hsp27 expression in the superficial layer was observed in all groups when compared to control group. CONCLUSION: The increased expression of Hsp27 in the basal layer observed during the OLP evolution and the less staining in the superficial layers in all cases of OLP suggest that hsp27 may have a role in the OLP pathogenesis.

p53 as a neoplastic biomarker in patients with erosive and plaque like forms of oral lichen planus.

AIM: Unstimulated whole salivary p53 was assessed in patients suffering from erosive and plaque-like form of oral lichen planus (OLP). MATERIALS AND METHODS: Eighteen patients with erosive form, 17 patients suffering from plaque-like form and 38 noninvolvement subjects were enrolled. The unstimulated whole saliva p53 level was assayed by ELISA. RESULTS: The mean concentration of salivary p53 was significantly higher in patients with plaque-like form compared to both patients with erosive form and the control group. CONCLUSION: We conclude that plaque like form of OLP is important in view of the potential for malignancy and is not safety form. CLINICAL SIGNIFICANCE: It seems that all forms of OLP must be considered accurately, should be followed up with biannual examinations, and if possible, assessment of salivary p53 every year.

Tumour necrosis factor-alpha gene polymorphisms and susceptibility to oral lichen planus.

OBJECTIVE: This study is aimed to investigate the association between OLP susceptibility and clinical type in the Thai population and three polymorphisms within the promoter region of the TNF-α at positions -863, -308 and -238 which have putative functional significances. MATERIALS AND METHODS: Genomic DNA from 75 Thai patients with OLP and 154 healthy controls were genotyped for TNF-α polymorphisms-- -863(rs1800630), -308(rs1800629), and -238(rs361525)--using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: We found a higher proportion of TNF-alpha-308 AA genotype (high producer genotype) among OLP patients (5/75; 6.67%) when compared to healthy controls (1/154; 0.65%; OR = 10.93; 95% CI = 1.21-251.9). For other polymorphisms (-863 and -238), we did not find any significant association with OLP development; this was also the case with haplotype analysis (-863/-308/-238). CONCLUSION: TNF-α-308AA may play a relevant role in the susceptibility and severity of OLP in the Thai population. However, further investigation of this study is needed.

The magnitude of the association between hepatitis C virus infection and oral lichen planus: meta-analysis and case control study.

Although hepatitis C virus (HCV) infection is associated with oral lichen planus (OLP), a case-control study and a meta-analysis were designed to investigate the magnitude of such an association. A total of 413 presumptive OLP patients (18-75 years) who referred to a dental clinic in Rasht (Iran) were consecutively selected. OLP was diagnosed clinically (typical forms) and histologically (atypical forms) by a calibrated examiner. A total of 487 adults (20-77 years) attending the same dental clinic were the controls. The two groups were homogeneous in terms of age, gender and occupation. Subjects were tested for anti-HCV antibodies. The odds ratio (OR) for OLP attributable to HCV infection was non-significant [OR 1.2, 95% confidence interval (95CI) 0.3-4.8], suggesting that the association between HCV and OLP was weak in the Iranian context. Meta-analysis of observational studies characteristics of primary studies were that cases were diagnosed clinically (only typical forms) and histologically and exposure was assessed through anti-HCV antibodies. Exposed/unexposed cases/controls were extracted and zero values were appropriately transformed. As much as 44 studies, including the present, were located. Publication bias could not be totally excluded. The pooled OR, estimated using the random-effect model, was 2.8 (95CI 2.4-3.2). Sensitivity analysis confirmed the robustness of results. Subgroup analysis showed non-significant differences between American/European and Asian/African studies. The fraction of global OLP cases associated with HCV (population attributable fraction) was 2.1% (95CI 1.9-2.2%). Although HCV and OLP were significantly associated, the majority of OLP patients were not affected by HCV.

Pathogenesis of oral lichen planus--a review.

Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory oral mucosal disease of unknown etiology. OLP presents as white striations, white papules, white plaques, erythema, erosions, or blisters affecting predominantly the buccal mucosa, tongue and gingiva. Both antigen-specific and non-specific mechanisms are hypothesized to be involved in the pathogenesis of oral lichen planus (OLP). Antigen-specific mechanisms in OLP include antigen presentation by basal keratinocytes and antigen-specific keratinocyte killing by CD8(+) cytotoxic T cells. Non-specific mechanisms include mast cell degranulation and matrix metalloproteinase activation in OLP lesions. These mechanisms may combine to cause T cell accumulation in the superficial lamina propria, basement membrane disruption, intra-epithelial T cell migration and keratinocyte apoptosis in OLP. The various hypotheses proposed for pathogenesis of oral lichen planus are discussed in this review.

DNA ploidy in oral lichen planus, determined by image cytometry.

BACKGROUND: The objective of this study was to use image cytometry to determine the degree and frequency of DNA ploidy in biopsies of reticular and atrophic-erosive oral lichen planus and to analyze 14 karyometric measurements of the nuclei of epithelial cells from each specimen. METHODS: A total of 40 slides were analyzed, each of them representing one biopsy of one oral lichen planus (OLP) lesion from each one of the 40 patients (cases) studied. Specimens were embedded in paraffin and comprised 20 slides of reticular oral lichen planus (group R) and 20 slides of atrophic-erosive oral lichen planus (group AE). RESULTS: Group R, the reticular lichen samples, had 18 diploid cases and two aneuploid cases. Group AE, the atrophic-erosive lichen samples, had 10 diploid cases, one tetraploid case, and nine aneuploid cases. Of the 14 karyometric measurements of the nuclei of OLP epithelial cells analyzed, the group R mean values for mean density and minimum density were significantly greater than the group AE mean values, and mean roundness in group AE was significantly greater than in group R (t-test: P < 0.05). CONCLUSIONS: The most common degree of DNA ploidy in OLP lesions was diploidy. Comparing the two groups (chi-square test of association P = 0.021) demonstrated that diploidy was associated with the reticular clinical form of OLP, while aneuploidy was associated with the atrophic-erosive clinical form of oral lichen planus.

A retrospective clinicopathological study of 550 patients with oral lichen planus in south-eastern Spain.

OBJECTIVES: This study describes the clinicopathological characteristics of a group of patients with oral lichen planus (OLP) in south-eastern Spain. MATERIALS AND METHODS: A retrospective descriptive study was made of 550 patients clinically and histopathologically diagnosed with OLP in the period 1991-2007. Patient gender, age, the prevalence of hepatitis C, symptoms and malignization were recorded. The clinical forms were classified as reticular-papular and atrophic-erosive. RESULTS: Of the 550 patients, 128 (23.3%) were men and 422 (76.7%) women. The mean age was 56.35 +/- 13.67 years (range 14-91). The prevalence of hepatitis C was 3.5%. The red clinical forms were the most frequent, with 359 cases (64.2%). The lesions were asymptomatic in 159 patients (28.9%). Five patients developed oral squamous cell carcinoma (0.9%); none of these subjects was smokers. CONCLUSIONS: Patients with OLP present different clinical manifestations. Women were more frequently affected by the disease, and the malignant transformation rate was under 1%.

[Potentially malignant disorders of the oral mucosa: terminology and classification]. / Affections potentiellement malignes de la muqueuse buccale: nomenclature et classification.

The last WHO expert workgroup recommended abandoning the distinction between potentially malignant lesions and conditions. The term to use is "potentially malignant disorders". Leukoplakia is the most common of these disorders, while erythroplakia is rather rare. The diagnosis is still made by excluding other documented white or red lesions. Despite progress in molecular biology, no marker allows predicting malignant transformation. These lesions are treated surgically with or without dysplasia. It is unknown if this surgery can really prevent transformation into squamous cell carcinoma. The potential malignancy of oral lichen planus is still debated. The risk of malignant transformation is lower than that of leukoplakia. No treatment may prevent this. Other potentially malignant conditions such as oral submucous fibrosis, actinic cheilitis, lupus, and immunodeficiency are rare.

Activation of nuclear factor-kappa B correlates with tumor necrosis factor-alpha in oral lichen planus: a clinicopathologic study in atrophic-erosive and reticular form.

BACKGROUND: Nuclear factor-kappa B (NF-kappaB) is believed to be involved in the pathogenesis of various inflammatory diseases, including oral lichen planus (OLP). The objective of the present study was to investigate the possible relationship between NF-kappaB activation and expression of tumor necrosis factor-alpha (TNF-alpha) in OLP and their expression pattern in relation to several clinical features. METHODS: Thirty OLP cases were divided into atrophic-erosive form (14 cases) and reticular form (16 cases) according to their clinical manifestations. The expression of NF-kappaB p65 and TNF-alpha of both two groups were investigated by immunohistochemical staining, and the percentage of positive cells was calculated in each case. Biopsies of 10 normal oral mucosa (NOM) also underwent the same procedure as controls. RESULTS: Nuclear factor-kappa B p65 nuclear staining was found in nuclei of basal and suprabasal epithelial keratinocytes in OLP, however, no positive staining was found in NOM. Positive TNF-alpha staining was detected in cytoplasm of basal epithelial keratinocytes in OLP, and only scattered staining was detected in NOM. Expression of NF-kappaB p65 and TNF-alpha were significantly different with respect to clinical forms and lesion sites (P < 0.05), except for genders (P > 0.05) in 30 OLP cases. NF-kappaB nuclear staining positively correlated (r = 0.676, P < 0.01) with TNF-alpha overexpression in OLP. CONCLUSIONS: Nuclear factor-kappa B activation and its correlation with overexpression of TNF-alpha may play an important role in pathogenesis of OLP. There might be a positive regulatory loop between NF-kappaB and TNF-alpha, which may contribute to inflammation in OLP; NF-kappaB may also protect epithelial keratinocytes from excessive apoptosis.

Course of oral lichen planus: a retrospective study of 808 northern Italian patients.

OBJECTIVES: To undertake a retrospective inspection of the general features, clinical presentation and outcome of 808 Italian patients with oral lichen planus (OLP), followed up from 6 months to 17 years. RESULTS: The mean age was 61 years for women (n = 493) and 58 years for men (n = 315). More than 20% of the total cases had liver abnormalities (n = 164) of which 83.5% infected with hepatitis C virus (n = 137). The reticular and plaque form were the predominant type, affecting almost 60% of patients. 12.3% of patients had also extraoral manifestation, taking into account the skin (n = 63) and genital (n = 24). Symptoms were present in 40% of the total patients. Only less than 2.47% of patients underwent remission, whereas 78% still had oral lesions at the end of the follow-up period. Treatment was directed towards almost 42% of the patients, mainly using topical corticosteroids. Oral squamous cell carcinoma developed in 15 patients, commonly arising on the lateral border of the tongue. CONCLUSION: This is one of the largest groups of OLP patients with such long a follow-up ever reported. We confirm the chronic nature of this disorder, rarely remissive and the treatment intend for alleviating symptoms. OLP is established to be a disease with small frequency of malignant transformation.

Implications on pathogenesis and risk of oral lichen planus neoplastic transformation: an ex-vivo retrospective immunohistochemical study.

AIMS: To evaluate OPN, MCM7, Ki-67, p53, Bcl-2 and 53BP1 presence, together with the abnormal adaptive CD4 and CD8 T-cell response markers expression in a series of oral lichen planus (OLP) affected patients and assess their combined contribution for a more objective disease classification. METHODS AND RESULTS: In this ex-vivo retrospective analysis, biopsy specimens from 28 adults with a clinical diagnosis of OLP at different progression degree (16 reticular, 2 plaque-like, 1 erosive and 9 mixed type) were collected. Sections were immunohistochemically investigated for the proinflammatory cytokine osteopontin (OPN), alpha-beta CD4 and CD8 positive T cells, DNA replication licensing factor (MCM7), proliferating cell marker (Ki-67), apoptotic and tumor antigen (p53), apoptosis modulator (Bcl-2) and cellular response regulator to double-strand breaks tumor suppressor p53-binding protein 1 expression. Statistical analysis revealed that 53BP1 is highly represented among the OLP study patients (p<0.05). Moreover, on the basis of the quantification results of the highly expressed parameters, two illness categories with different severity were evidenced. The classification hypothesis was confirmed by i) OLP lesion persistence, ii) the development of oral severe lesions in the patients belonging to high grade activity OLP group (HGA-OLPs) and iii) the ascertainment of the same evidence both in the oral squamous cell tumor controls (OSCC) and in HGA-OLP cases. CONCLUSION: This study completes the scenario with respect to early detection, thanks to a more precise histological analysis, for rationalizing the clinical and histological findings toward a sharable international disease scoring system.