Xuemin Shen

Two stem cell markers, ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1, predict the transformation of oral leukoplakia to cancer: a long-term follow-up study.

Although oral leukoplakia (OL) is the best‐known potentially malignant disorder, the risk of OL malignant transformation is difficult to assess. ATP‐binding cassette, G2 subfamily (ABCG2) and BMI‐1 are stem cell markers that have been found to be associated with head and neck tumorigenesis. The objective of the current study was to evaluate the usefulness of ABCG2 and BMI‐1 in predicting OL transformation.

Expression patterns of cancer stem cell markers ALDH1 and CD133 correlate with a high risk of malignant transformation of oral leukoplakia.

Molecular markers for predicting oral cancer development in premalignant oral leukoplakia (OL) are urgently needed. The objective of this study was to examine the expression patterns of cancer stem cell markers ALDH1 and CD133 in samples from patients with OL, and determine their prognostic values for subsequent development of oral cancer. Immunohistochemistry for ALDH1 and CD133 was performed in samples from a cohort of 141 patients with biopsy‐proven OL who received a mean follow‐up of 5.5 years. Patient clinicopathologic and follow‐up data were analyzed. Expression of ALDH1 and CD133 was observed in 54 (38.3%) and 32 (22.7%) of 141 patients with OL, respectively. Kaplan–Meier analysis showed that 48.1% patients with ALDH1‐positivity developed oral cancer compared with 12.6% those with ALDH1‐negativity (p < 0.001). Meanwhile, 59.4% patients with CD133‐positivity developed oral cancer compared with 16.5% those with CD133‐negativity (p < 0.001). Multivariate analysis revealed that ALDH1 and CD133 expression was associated with 4.17‐fold [95% confidence interval (CI), 1.96–8.90; p < 0.001] and 2.86‐fold (95% CI, 1.48‐5.55; p = 0.002) increased risk of OL transformation, respectively. Collectively, these data demonstrated for the first time that the expression of ALDH1 and CD133 correlated with malignant transformation in a large series of patients with OL who received a long‐term follow‐up, which suggests that they may serve as predictors to identify OL with a high risk of oral cancer development.

Altered microRNA expression profile with miR‐27b down‐regulation correlated with disease activity of oral lichen planus

BACKGROUND Increasing evidence indicates that microRNAs (miRNAs) play a vital role in the pathogenesis of inflammatory and autoimmune diseases. The objective of this study was to investigate the altered miRNA expression profile in patients with oral lichen planus (OLP) and determine the miR-27b expression. METHODS We compared miRNA expression patterns in oral biopsy specimens from patients with OLP (n=3) with those from normal controls (n=3) using microarray technology. We further assessed the miR-27b expression in specimens from patients with OLP (n=53) against controls (n=34) using real-time quantitative PCR (RT-QPCR), and miR-27b expression in specimens from patients with OLP (n=15) against controls (n=12) using in situ hybridization (ISH). RESULTS Using microarray analysis, a total of 46 differentially expressed miRNAs with more than 2-fold change were identified, including 8 up-regulated and 38 down-regulated miRNAs. Both RT-QPCR and ISH analyses revealed that miR-27b was significantly down-regulated in OLP tissue, and miR-27b expression was even more suppressed in atrophic-erosive OLP than in reticular OLP. In addition, miR-27b was found to be expressed in the epithelial keratinocyte layer of both normal and OLP tissues. CONCLUSION These data indicate that miRNAs may be the novel candidate biomarkers for the implication of miRNAs in the pathogenesis of OLP.

Immunoexpression of Interleukin-22 and Interleukin-23 in Oral and Cutaneous Lichen Planus Lesions: A Preliminary Study

Interleukin- (IL-) 22 is the signature cytokine of T-helper (Th) 22 cells, and IL-23 is required for IL-22 production. The objective of this study was to examine the immunoexpression of IL-22 and IL-23 in archival paraffin-embedded biopsy specimens from oral LP (n = 42) and cutaneous LP (n = 38) against normal control tissues. The results showed that the percentage of cells expressing IL-22 and IL-23 in LP were significantly higher in LP compared to controls, respectively (both P < 0.001). The correlation between IL-22 and IL-23 expression was significant (P < 0.05). Moreover, the percentage of cells expressing IL-22 and IL-23 in oral LP were significantly higher than cutaneous LP (P < 0.05). Collectively, our findings demonstrated that the increased expression of IL-22 and IL-23 in LP lesions could play roles in the pathogenesis of LP. Moreover, oral LP expressing IL-22 and IL-23 was higher than cutaneous LP, probably due to Th22 cells as an important component of oral mucosal host defense against oral microbiota and tissue antigens. This may be associated with the difference in clinical behaviour of the two variants of the disease.

Malignant transformation of oral verrucous leukoplakia: a clinicopathologic study of 53 cases.

BACKGROUND Oral verrucous leukoplakia (VL) is one of the non-homogenous oral leukoplakias. The objective of this study was to investigate the clinicopathologic features of VL and identify the clinicopathologic risk factors that might be associated with VL malignant transformation from China. METHODS Among 1541 patients with oral leukoplakia, a total of 53 patients with clinical and histopathologic diagnosis of VL between 1996 and 2009 were reviewed retrospectively in our hospital. RESULTS Of the 53 patients, 11 (20.8%) with VL were observed to develop cancer in the study period. The average age at diagnosis was 59.8 years with a male/female ratio of 1.7:1. Tongue was the predominant site (41.5%). Multivariate regression analysis revealed that the elderly patients (>65 years old) were associated with 8.36-fold [95% confidence interval (95% CI), 1.45-48.09; P = 0.017] increased risk of malignant transformation compared with the non-elderly patients. The lesion located on gingiva was associated with 20.81-fold (95% CI, 1.94-222.80; P = 0.012) increased risk of malignant transformation compared with tongue. However, the gender, smoking, alcohol intake, and epithelial dysplasia were not risk factors. CONCLUSION Clinicopathologic features of VL in China were elucidated. The utilization of age and lesion site at diagnosis as significant factors for evaluating malignant transformation risk in patients with VL was suggested. Further studies are required to investigate the roles of the potential risk factors in the VL malignant transformation.

Prevalence and distribution of oral mucosal lesions: a cross-sectional study in Shanghai, China

BACKGROUND An epidemiological study on the oral mucosal lesions (OMLs) in general population from China was scarce. The objective of this study was to investigate the prevalence and distribution of OMLs in Shanghai, China and to evaluate their association with demographic factors and smoking/drinking habits based on a large scaled population on a wide spectrum. METHODS In this population-based cross-sectional study, 11054 community-dwelling individuals (M/F: 5140/5914; age range, 1-96 years) were randomly selected and examined according to WHO criteria. RESULTS The prevalence of OMLs was 10.8% in this study. A total of 1192 (M/F: 543/649; mean age, 56.9 years) individuals were presented with different types of OMLs. The most common type of OMLs was fissured tongue (prevalence of 3.15%), followed by recurrent aphthae (1.48%), traumatic ulcer (1.13%), and angular cheilitis (0.86%). The two most common potentially malignant disorders were oral lichen planus (0.81%) and leukoplakia (0.22%). Regression analysis revealed that the elderly age, smoking, and alcohol intake were statistically significant risk factors of OMLs with emphasis on leukokeratosis, leukoplakia, and lichen planus. CONCLUSION The prevalence and distribution of OMLs were elucidated in an eastern area of China, and the importance of tobacco and alcohol in the pathogenesis of OMLs was evidenced. Our data have provided baseline information about epidemiologic aspects of OMLs that can be valuable in organized program targeting on oral health and hygiene.

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.