[Effects of Fusobacterium nucleus derived outer membrane vesicles on claudin-4 expression in oral epithelial cells].

PURPOSE: To investigate the effect of outer membrane vesicles (OMVs) secreted by Fusobacterium nucleatum (F.n) on Claudin-4 of human oral keratinocytes (HOK) and oral epithelial barrier function. METHODS: Fusobacterium nucleatum was cultured under anaerobic conditions. The OMVs were extracted by dialysis and characterized by nanosight and transmission electron microscopy (TEM). HOK were stimulated with OMVs at different mass concentrations(0-100 µg/mL) for 12 h, and stimulated with 100 µg/mL OMVs for 6 h and 12 h respectively. The expression of Claudin-4 at gene and protein level was analyzed by RT-qPCR and Western blotting. Inverted fluorescence microscope was used to observe co-localization of HOK and OMVs and localization and distribution of Claudin-4 protein. Human oral epithelial barrier was constructed by Transwell apical chamber. Transepithelial electrical resistance(TER) of barrier was measured with a transmembrane resistance measuring instrument(EVOM2), and the permeability of the barrier was evaluated by transmittance of fluorescein isothiocyanate-dextran(FD-4). Statistical analysis was performed with GraphPad Prism 8.0 software package. RESULTS: Compared with the control group, the expression of Claudin-4 at protein and gene level in the HOK of OMVs stimulated group was significantly reduced (P＜0.05), and immunofluorescence showed that the continuity of Claudin-4 fluorescence among cells was destroyed. OMVs stimulation decreased TER value of oral epithelial barrier(P＜0.05) and increased the transmittance of FD-4(P＜0.05). CONCLUSIONS: OMVs derived from Fusobacterium nucleatum may damage oral mucosal epithelial barrier function through inhibiting the expression of Claudin-4.

[Correlation between low expression of Hsp90 protein in keratinocytes and the number of small extracellular vesicles and its potential clinical significance].

PURPOSE: To investigate the correlation between the level of heat shock protein 90(Hsp90) and the amount of small extracellular vesicles(sEVs) in keratinocytes. METHODS: Human keratinocytes(HaCaT) were cultured in vivo and divided into wild-type group, short hairpin RNA interference group (shRNA group, low expression of Hsp90), and 17-Allylamino-17-demethoxygeldanamycin group (17-AAG group, Hsp90 protein inhibitor). sEVs were isolated from culture system by ultracentrifugation, and their morphological characteristics were observed under transmission electron microscopy (TEM). Western blotting was applied to identify the biological characteristics of sEVs. The number of sEVs particles was detected by nanoparticle tracking analysis (NTA). GraphPad Prism8.0 software was used to analyze the difference in the number of sEVs among the groups by t test (non-parametric Mann-Whitney U test). RESULTS: HaCaT-derived sEVs, obtained by ultracentrifugation, were consistent with the criteria of morphological and biological identification. No expression of Hsp90 protein was detected in HaCaT-derived sEVs. When interfered with Hsp90-shRNA, the number of sEVs were significantly increased. On day 5, the sEVs number of shRNA-interfering group was (177.4±4.18)×108(n=3), while that of vector group was (82.34±4.83)×108(n=3), and the difference was statistically significant (P＜0.0001). After 5 days of inhibition with 17-AAG, the sEVs number of 17-AAG group was （652.5±26.73）×108(n=3) and that of control group was (262.22±5.44)×108(n=3), the difference was statistically significant (P＜0.000 1). CONCLUSIONS: Low expression of Hsp90 protein can promote the secretion of sEVs in HaCaT cells. sEVs may be involved in the transfer of molecules between epithelial cells and immune cells.

Long-term clinical outcomes of short implant (6mm) in relation to Implant Disease Risk Assessment (IDRA).

AIM: To evaluate the long-term survival of short implants and to investigate the association of the Implant Disease Risk Assessment (IDRA) with the occurrence of biological complications. MATERIAL AND METHODS: This study was designed as a cohort study with a median follow-up of 10.0 years. Patients who had received 6-mm implants were reviewed and assigned into low-, moderate-, and high-risk groups (Group L, M, and H) based on the IDRA tool. The implant survival, biological complications, soft tissue condition, hardware complications, and marginal bone loss (MBL) were evaluated. Kaplan-Meier curves and Cox regression were performed for survival analysis. RESULTS: A hundred and ten patients were included. The overall cumulative survival rate was 90.9% (L:100.0%, M: 93.3%, and H: 80.6%). A higher risk profile was significantly associated with a decreased implant survival (hazard ratio: 4.11, 95% CI: 1.17-14.36, p < .05). Higher risk profile (hazard ratio: 2.63, 95% CI: 1.32-5.25, p < .05) was a potential risk factor for biological complications. At follow-up, significant differences in bleeding index, modified plaque index, and peri-implant probing depth were found among groups (p < .01). No significant difference was found in MBL. CONCLUSION: Acceptable long-term clinical outcomes could be achieved after 10 years for short implants. Despite a statistically nonsignificant difference in MBL, patients with a high-risk profile of IDRA seem to be at greater risk of implant loss and biological complications.

Protein disulfide isomerase family A member 3 expression is upregulated in tissue-derived extracellular vesicles in oral lichen planus and oral lichenoid lesions.

OBJECTIVES: The aim of this study was to identify the tissue-derived extracellular vesicles immunogen involved in the pathogenesis of oral lichen planus (OLP) and its variation oral lichenoid lesions (OLL). DESIGN: Six pooled tissue-derived extracellular vesicles from participants with OLP/OLL and three from healthy controls were isolated and enriched. The extracellular vesicles were characterized with transmission electronic microscopy, nanoparticle tracking analysis and western blotting. Proteins from extracellular vesicles were identified with proteomics analysis and differentially expressed proteins (DEPs) were further identified with a 2-fold (p < 0.05) increase or a 0.5-fold decrease. RESULTS: A total of 1805 peptides and 141 proteins were identified. Ten DEPs were further identified, with five upregulated proteins of fibrinogen alpha chain, lamin isoform A, 40S ribosomal protein, protein disulfide isomerase family A member 3 (PDIA3) and elongation factor 1-alpha 1, and five downregulated proteins of plakophilin-1, katanin p80 repeat-containing subunit B1, collagen alpha-3 chain, mitochondrial 2-oxoglutarate/malate carrier protein and guanine nucleotide-binding protein subunit gamma-12. PDIA3 was found to be immune-associated and to be involved in the antigen processing and presentation pathway. The upregulation of PDIA3 was confirmed in a verification cohort composed of three pairs of OLP/OLL-extracellular vesicles and healthy controls-extracellular vesicles with western blotting. CONCLUSIONS: Protein disulfide isomerase family A member 3 in extracellular vesicles may play a significant role in the local immune responses and the pathogenesis of oral lichen planus and oral lichenoid lesions.

Management of oral leukoplakia by ablative fractional laser-assisted photodynamic therapy: A 3-year retrospective study of 48 patients.

OBJECTIVES: This study aimed to review the results of oral leucoplakia (OL) using ablative fractional laser-assisted photodynamic therapy (AFL-PDT) and to further evaluate the risk factors for recurrence and malignant transformation. MATERIALS AND METHODS: Forty-eight patients diagnosed with OL using histopathology were enrolled in this study. All patients received one session of AFL-PDT. Therapeutic efficacy was evaluated 1 month posttreatment. Follow-up was scheduled every 3 months in the first year and every 6 months thereafter. RESULTS: An overall positive response rate of 87.5% (42/48) was achieved, including 62.5% (30/48) complete responses and 25.0% (12/48) partial responses. During the 3-year follow-up period, the recurrence and malignant transformation rates were 37.5% (18/48) and 8.3% (4/48), respectively. Lesions on gingiva/palate seemed to be associated with recurrence (p < 0.001; odds ratio [OR]: 1.64, 95% confidence interval [CI]: 1.13-2.37). The severity of epithelial dysplasia (p = 0.02; OR: 2.93, 95% CI: 1.96-4.42) and recurrence (p = 0.016; OR: 3.14, 95% CI: 2.04-4.84) were associated with a predisposition to malignant transformation. CONCLUSIONS: AFL-PDT is an effective management of OL, but requires close follow-up. OL lesions on the gingiva/palate are predisposed to recurrence. OLs that recur with moderate/severe epithelial dysplasia have a higher risk of transforming into oral squamous cell carcinoma.

Intralesional and peripheral plasma of oral lichenoid reactions exhibit different cytokine profiles: A preliminary study.

BACKGROUND/PURPOSE: Oral lichenoid reactions (OLRs) are commonly characterized by the infiltration and activation of inflammatory cells at the interface of the oral mucosa. This study aimed to compare the cytokine profiles between intralesional and peripheral plasma from patients with OLRs and elucidate the cytokine profile in the OLR microenvironment. MATERIALS AND METHODS: A total of 26 paired intralesional and peripheral plasma samples were collected from patients with OLRs. A panel of 15 cytokines was measured using a Luminex assay. The reticular, erythema, and ulcerative score was used to evaluate the degree of OLR severity. RESULTS: IL-10 was detected in a fewer number of intralesional samples (19/26) compared to peripheral samples (26/26, p = 0.01). The intralesional plasma exhibited significantly elevated levels of granzyme B (median 108.94 vs. 16.00), TGF-ß1 (mean 30448.92 vs. 10199.04), TGF-ß2 (mean 1659.73 vs. 1308.49), and TGF-ß3 (mean 914.33 vs. 573.13) compared to the peripheral plasma (p = 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively). The levels of intralesional IL-2 (median 2.84 vs. 3.45, p = 0.019) and TNF-α (median 7.66 vs. 10.34, p = 0.048) were significantly lower in the intralesional plasma compared to the peripheral plasma. CONCLUSION: The intralesional concentrations of granzyme B and TGF-ß were elevated, whereas IL-2 and TNF-α were decreased in the OLR microenvironment compared to the peripheral plasma. These findings may contribute to establishing a panel of biomarkers that can be used to monitor the disease activity of OLRs in a large cohort study in future.

[Experimental study on the structure and immune cell phenotypes of the lymphoid tissues in oral lichenoid lesions].

PURPOSE: To evaluate the existence of tertiary lymphoid structures(TLS) in oral lichenoid lesions and its compositional characteristics of immune cells. METHODS: Tissue samples of normal oral mucosa, oral lichen planus (OLP) and oral lichenoid tissue reaction(OLTR) were collected, thirty cases in each group. Hematoxylin-eosin(H-E) staining was performed to identify the TLS-like structures, and immunohistochemistry (IHC) staining was applied to assess the structure and amount of infiltrating CD3+ T cells, CD19+, CD20+ B cells, CD21+ follicular dendritic cells (FDC), Bcl-6+ germinal centers, CD34+ PNAd+ venules and CD34+ Gp36+ micro lymphatic vessels in TLS of OLL. Histopathology and molecular markers were used to evaluate the morphological performance of TLS in OLL. Chi-square test (Fisher exact probability method) was applied to compare the proportion of TLS in each group; integral optical density (IOD) method was used to calculate the expression level of each molecular marker, nonparametric t test (Mann-Whitney U test) was employed to analyze their difference. Statistical analysis was performed with GraphPad Prism 7.0 software. RESULTS: In OLP group and OLTR group, 46.7% (14/30) and 23.4% (7/30) cases had TLS-like structures, respectively. The frequency of TLS-like structures was not correlated with the type of disease(P>0.05). Compared with the control group, the molecular markers in OLP group and OLTR group were highly expressed, and the expression of CD19, CD20, and CD21 in OLP group had morphological and structural characteristics of TLS. The expression of Bcl-6(mean and standard deviation of IOD were 15 498±15 108 vs. 1 841±2 276, P<0.0001), CD20 (13 067±9 049 vs. 7 695±5 159, P<0.05), CD21 (13 968±14 560 vs. 2 552±2 584, P<0.0001), PNAd (10 328±10 383 vs. 1 756±1 570, P<0.0001) and Gp36 (12 778±12 390 vs. 2 313±2 578, P<0.0001) showed significant differences between OLP and OLTR tissues, but it could not be used as the criteria for identifying the type of diseases without morphological characters. CONCLUSIONS: TLS exists in OLL lesions, mainly presented as non-classical forms. The classical forms can be occasionally found. CD20 and CD21 can be used as the biomarkers to identify the TLS in OLL. TLS can not be used as the diagnosing criteria for identifying OLP or OLTR.

[Experts recommendation on the diagnosis and treatment of oral mucosal diseases during prevention and control stage of the novel coronavirus infection].

The announcement of National Health Commission on January 20, 2020 (No. 1 of 2020) has included Novel Coronavirus Pneumonia(NCP) into the B class infectious diseases according to the law of the People's Republic of China on the prevention and control of infectious diseases, and has been managed as A class infectious diseases. People's governments at all levels and health administration departments have been paying high attention to it, and medical and health institutions have taken a series of prevention and control measures according to the law to prevent and control the spread of NCP. In the process of combating the outbreak of NCP, how to protect the oral mucosal disease physicians normatively, how to ensure hand and environmental cleaning and disinfection; how to carry out triage of the patients with oral mucosal disease accompanied by fever reasonably; how to carry out oral mucosal disease patients'self-care and self-management during this stage, are the practical problems that all levels of medical institutions and medical workers and patients will meet. For these three problems, we invited the experts from the Society of Oral Medicine, Shanghai Stomatological Association and the Oral Mucosal Disease Specialist Alliance Organization of Shanghai Ninth People's Hospital Group to write the recommendation on the diagnosis and treatment of oral mucosal disease during prevention and control stage of novel coronavirus infection, in order to provide references for oral mucosal disease medical physicians and patients in this special period. This recommendation will be updated according to the situation of epidemic prevention and control in China and the new relevant diagnosis and treatment plans.

Potential association between Fusobacterium nucleatum enrichment on oral mucosal surface and oral lichen planus.

OBJECTIVE: We determined the bacterial community structure of the buccal mucosa in patients with oral lichen planus (OLP) and evaluated the potential association of Fusobacterium nucleatum with OLP. SUBJECTS AND METHODS: We collected buccal mucosal swab samples of patients with OLP (n = 20) and healthy controls (n = 10) and performed 16S rRNA gene sequencing and real-time PCR to determine potentially different bacteria. Damaged and adjacent non-damaged mucosal swab samples of 25 OLP patients were used to detect the amount of F. nucleatum by real-time PCR. RESULTS: Compared with healthy controls, enrichment of Fusobacterium and Granulicatella was more abundant in patients with OLP (p = .0146 and 0.0034). The abundance of Fusobacterium and F. nucleatum was significantly enriched on buccal mucosa of patients with OLP compared with healthy controls (p = .0043 and 0.0235). Compared with adjacent non-damaged buccal mucosa of OLP patients, the amount of F. nucleatum in the damaged mucosa was significantly increased (p = .001). We examined third-level KEGG pathways for bacteria on mucosal surface and found that genes controlling sporulation and ether lipid metabolism were enriched in patients with OLP. CONCLUSIONS: A high amount of F. nucleatum may be associated with OLP. Further studies are required to investigate the precise association of F. nucleatum with OLP.

[Atrophic glossitis is attributed to cobalamin deficiency].

PURPOSE: To analyze the causes of atrophic glossitis(AG) and to explore the relationship between AG and serum cobalamin, folate levels. METHODS: A total of 213 patients with AG treated from Jan.1979 to Jun. 2010 were analyzed for the causes of AG. Serum cobalamin, folate levels and complete blood count were tested in newly enrolled AG patients from Sep. 2010 to Aug. 2011. All data were analyzed with SPSS 16.0 software package for Student's t test. RESULTS: There were 97 AG patients (45.4%) suffering from megaloblastic anemia (MA)/ macrocytosis. Among the 72 newly enrolled AG patients, fifty had cobalamin deficiency. Meanwhile, serum folate levels were increased in cobalamin deficiency group. CONCLUSIONS: Cobalamin deficiency is the common cause both of MA/macrocytosis and AG, also may be the main cause of AG. Furthermore, AG may be the early clinical manifestation of cobalamin deficiency.

A retrospective clinicopathological study on oral lichen planus and malignant transformation: Analysis of 518 cases

Objective: To investigate the epidemiological and clinical characteristics of a relatively large cohort of patients with oral lichen planus (OLP) from eastern China. Study design: A total of 518 patients with histologically confirmed OLP in a long-term follow-up period (6 months-21.5 years) were retrospectively reviewed in our clinic. Results: Of the 518 patients, 353 females and 165 males were identified. The average age at diagnosis was 46.3 years (range 9-81 years) with the buccal mucosa being the most common site (87.8%). At initial presentation, white lichen and red lichen was seen in 52.3% and 47.7% patients, respectively. Of these, 5 (0.96%) patients previously diagnosed clinically and histopathologically as OLP developed oral cancer. All of them were the females with no a history of smoking or alcohol use. Conclusions: Clinical features of eastern Chinese OLP patients were elucidated. Notably, approximately 1% of OLP developed into cancer, which provides further evidence of potentially malignant nature of OLP (AU)

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A retrospective clinicopathological study on oral lichen planus and malignant transformation: analysis of 518 cases.

OBJECTIVE: To investigate the epidemiological and clinical characteristics of a relatively large cohort of patients with oral lichen planus (OLP) from eastern China. STUDY DESIGN: A total of 518 patients with histologically confirmed OLP in a long-term follow-up period (6 months-21.5 years) were retrospectively reviewed in our clinic. RESULTS: Of the 518 patients, 353 females and 165 males were identified. The average age at diagnosis was 46.3 years (range 9-81 years) with the buccal mucosa being the most common site (87.8%). At initial presentation, white lichen and red lichen was seen in 52.3% and 47.7% patients, respectively. Of these, 5 (0.96%) patients previously diagnosed clinically and histopathologically as OLP developed oral cancer. All of them were the females with no a history of smoking or alcohol use. CONCLUSIONS: Clinical features of eastern Chinese OLP patients were elucidated. Notably, approximately 1% of OLP developed into cancer, which provides further evidence of potentially malignant nature of OLP.

Malignant transformation of oral epithelial dysplasia: clinicopathological risk factors and outcome analysis in a retrospective cohort of 138 cases.

AIMS: To explore the usefulness of a new binary system of grading dysplasia proposed by the World Health Organization and to identify significant risk factors for malignant transformation in a long-term follow-up cohort of patients with oral epithelial dysplasia. METHODS AND RESULTS: A total of 138 patients with histologically confirmed oral dysplasia between 1978 and 2008 were reviewed retrospectively in our department. The mean follow-up period was 5.1 years. Of these dysplasias, 37 (26.8%) developed into cancer, with a mean duration of 4.6 years. Cox regression analysis revealed that high-grade dysplasia was an independent risk factor for transition, but age, gender, lesion site, diet habit, smoking and alcohol intake were not risk factors. High-grade dysplasia was associated with a 2.78-fold (95% confidence interval 1.44-5.38; P = 0.002) increased risk of transition, as compared with low-grade dysplasia. Consistently, high-grade dysplasia had a significantly higher incidence of malignancy than low-grade dysplasia by Kaplan-Meier analysis (log-rank test, P = 0.001). CONCLUSIONS: The utilization of high-grade dysplasia as a significant indicator for evaluating malignant transformation risk in patients with potentially malignant lesions is suggested; this may be helpful to guide treatment selection in clinical practice.

The high expression level of programmed death-1 ligand 2 in oral lichen planus and the possible costimulatory effect on human T cells.

BACKGROUND: Oral lichen planus (OLP) is a T-cell-mediated chronic autoimmune disease whose precise etiology is unknown. The recently identified costimulatory programmed death-1 (PD-1) molecule and its ligands, PD-L1 and PD-L2, have been identified as CD28-B7 family molecules and constitute a regulatory pathway of potential therapeutic use in immune-mediated diseases. METHODS: We examined the expression of two ligands of PD-1 at both the protein and gene level in the focal mucosa and peripheral blood of OLP patients using immunohistochemistry and real-time PCR. Next, we used the PD-L2.Ig fusion protein and observed its effects on T cells, which were co-cultured with IFN-γ-treated keratinocytes (KCs) in the presence of PHA. RESULTS: We found that the expression of PD-L2 at both the gene and protein level was statistically different in peripheral blood and local lesion tissue of patients with OLP compared to the normal controls. The proliferation ability of T cells and the expression level of IFN-γ in the supernatant of the above co-culture model were significantly augmented (P < 0.05). PD-L2.Ig fusion protein significantly aggravated the apoptosis of T cells, inhibited the proliferation of T cells and decreased the release levels of IL-2 and IFN-γ in the model (P < 0.05). CONCLUSION: These data show that the increased expression of PD-L2, as a costimulatory molecule, may have an important modulatory function on the local immune responses of OLP in vivo.

[Establishment of a correlated cell model of oral lichen planus in vitro].

PURPOSE: To establish a correlated cocultured model of keratinocytes and T lymphocytes in vitro to simulate the immune response circumstance of oral lichen planus(OLP) lesions. METHODS: Keratinocytes prepared with enzyme digestion from normal oral mucosa and T lymphocytes prepared with negative isolation procedure by magnetic beads were co-cultured. Proliferation of T lymphocytes in cocultured cells was detected using MTT assay and the expression of IFN-γ was detected by ELISA. All the results were analyzed with independent samples t test using SAS6.12 software package. RESULTS: The proliferation level of T lymphocytes in the cocultured group of T lymphocytes and keratinocytes which expressed PD-L1 and PD-L2 was higher than that in the group of T lymphocytes (P < 0.05). The expression of IFN-γ in the cocultured group was significantly higher than that in the group of T lymphocytes (P < 0.01). CONCLUSIONS: The cocultured model of T lymphocytes and keratinocytes which express PD-L1 and PD-L2 can simulate the immune response circumstance of OLP lesions to a certain extent. Supported by National Natural Science Foundation of China (30872888),Research Fund of Science and Technology Commission of Shanghai Municipality(08DZ2271100) and Shanghai Leading Academic Discipline Project (S30206).

[A retrospective analysis on the malignant transformation rate, time and risk factors of oral leukoplakia].

PURPOSE: A retrospective analysis was made on the oral leukoplakia (OLK) patients archived from 1978 to 2009 at the Department of Oral Medicine, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University, to analyze the malignant transformation of oral leukoplakia and its influential factors. METHODS: The data was studied with the SAS6.12 software package, using the methods of survival analysis and Cox regression to acquire malignant transformation rate (MTR) and malignant transformation time (MTT). RESULTS: According to the archived files, there were 576 cases of OLK with 350 males and 226 females. Among them, 66 cases (33 males and 33 females) developed OSCC, the total MTR was 11.46%. Two hundred and sixty-seven cases were suitable for survival analysis and Cox regression. The 1-year MTR was (0.40 ± 0.40)%, (0.86 ± 0.61)% (life-table method/product-limit method); the 2-year MTR went up to (2.84 ± 1.15)%, (2.93 ± 1.18)% and the 5-year MTR was as high as (11.28 ± 2.70)%, (11.31 ± 2.71)%. In Cox regression model, location of lesion and age were the main factors that affected OLK's transformation to OSCC. CONCLUSIONS: The MTR of OLK is related to the follow-up time; The lesion site and age are the most important risk factors. Supported by Research Fund of Science and Technology Commission of Shanghai Municipality (08DZ2271100), Shanghai Leading Academic Discipline Project (S30260) and Research Fund of Shanghai Municipal Education Commission (JDY-07061).

[T cell receptor BV gene preferential usage in oral lichen planus].

PURPOSE: To identify the T cell receptor (TCR) structural characteristics of infiltrating T cells derived from the lesional tissues of oral lichen planus (OLP) patients. METHODS: BV gene distribution analysis was performed quantitatively in OLP patients using real-time polymerase chain reaction. The data was analyzed by Mann-Whitney U test using GraphPad Prism version 5.00 software. RESULTS: The usage toward BV4, BV14 and BV18 in the lesional tissues from 43 OLP patients was significantly higher than the usage toward these BV genes in the peripheral blood from 39 OLP patients. CONCLUSION: Infiltrating T cells derived from the lesional tissues in a cohort of Chinese OLP patients display preferential usage toward BV4, BV14 and BV18. It indicates that the T cells bearing BV4, BV14 and BV18 genes play a very important role in the etiology and pathogenesis of OLP. Supported by National Natural Science Foundation of China (30872888), Research Fund of Science and Technology Commission of Shanghai Municipality (06ZR14060) and Shanghai Leading Academic Discipline Project (S30206).

[Study on the expression and potential effect of PD-L1mRNA and PD-L2mRNA in oral lichen planus].

PURPOSE: To study the expression of PD-L1 and PD-L2mRNA in oral lichen planus(OLP) patients' peripheral blood and focal mucosa, and the different expression of target molecules in gene level in different clinical and pathological OLP groups. METHODS: The expression of PD-L1 and PD-L2 mRNA in OLP patients, which included 35 reticular and 25 atrophic-erosive OLP patients, 38 cases without dysplasia and 22 cases with dysplasia, was examined by real-time PCR. Peripheral blood and mucosa from 10 volunteers were used as control. All the results were analysed with Wilcoxon test by SAS.6.12 software package. RESULTS: The expression of PD-L2mRAN, but not PD-L1, was significantly higher in oral mucosa of OLP patients (P<0.01), while decreased in OLP patients' peripheral blood (P=0.0415). The gene expression of PD-L2 differed between different clinical types, and had highly significant correlation between the OLP patients' focal mucosa and peripheral blood(r=0.6976, P<0.0001). CONCLUSIONS: PD-L2 may have some potential effect on the pathogenesis of OLP at systemic and local level.

Malignant transformation of oral leukoplakia: a retrospective cohort study of 218 Chinese patients.

BACKGROUND: Oral leukoplakia (OL) is the best-known potentially malignant disorder. A new binary system to grade dysplasia was proposed by WHO, but the biological significance in predicting malignant transformation risk is unknown. The objective of this study is to estimate the rate of malignant transformation in a long-term follow-up cohort, explore the usefulness of the new binary system of grading dysplasia and identify significant risk factors of OL malignant transformation in China. METHODS: A total of 218 patients with clinical and histopathologic diagnosis of OL were retrospectively reviewed. They were selected among all archived files at the Department of Oral Mucosal Diseases, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The mean follow-up period was 5.3 years. RESULTS: Among 218 cases, 39 (17.9%) OL patients developed oral cancer, with a mean duration of 5.2 years. Cox regression analysis revealed that dysplasia was an independent risk factor for OL malignant transformation, but age, gender, lesion site, diet habit, smoking and ethanol intake were not risk factors. High-risk dysplastic OL was associated with a 4.57-fold (95% confidence interval, 2.36-8.84; P < 0.001) increased risk of malignant transformation, compared with low-risk dysplasia. Consistent with this result, high-risk dysplastic OL had significantly higher malignant incidence than low-risk dysplasia, particularly during the first 2-3 years of follow-up, by Kaplan-Meier analysis (Log-rank test, P < 0.001). CONCLUSIONS: The new binary system's function in predicting OL malignant transformation risk was investigated in this survey. The utilization of high-risk dysplasia as a significant indicator for evaluating malignant transformation risk in patients with OL was suggested, which may be helpful to guide treatment selection in clinical practice.