Caveolin-1 expression in oral lichen planus, dysplastic lesions and squamous cell carcinoma.

Caveolin-1(Cav-1), the main part of caveolae structure, is supposed to play a role in pathogenesis of many human tumors. Since oral lichen planus (OLP) is considered as a potential premalignant disease, this study evaluated Cav-1 expression in OLP in comparison with benign hyperkeratosis, dysplastic epithelium and oral squamous cell carcinoma (OSCC), to investigate its possible role in pathogenesis and malignant transformation of OLP. In this cross-sectional retrospective study, immunohistochemical expression of Cav-1 in the epithelial component and stroma was evaluated in 81 samples, including 12 cases of hyperkeratosis, 24 OLP, 22 epithelial dysplasia, and 23 OSCC samples. Correlations between Cav-1 expression and clinicopathological variables were evaluated statistically. Positive Cav-1 staining was found in 58% of OLP, 91% of hyperkeratosis, 100% of epithelial dysplasia, and 95% of OSCC samples. OSCC showed the highest Cav-1 expression and OLP had the lowest (P=0.001). The intensity of staining was significantly increased in stepwise manner from OLP to OSCC (P=0.001). Expression of Cav-1 was related to the grade of samples in OSCC and dysplastic samples (P=0.04). Based on the findings, it was concluded that Cav-1 may play a role in the pathogenesis of OLP and carcinogenesis of SCC, but its role in malignant transformation of OLP is not confirmed. Further studies are needed to evaluate its potential therapeutic function in OLP and SCC.

Jaafari-Ashkavandi Z ，Aslani E 《-》

Cathepsin-B and caveolin-1 gene expressions in oral lichen planus and oral squamous cell carcinoma.

Given the importance of the role of cellular changes in the prognosis and diagnosis of malignancies of the head and neck, we examined in this study the gene expressions of cathepsin-B (Cat-B) and caveolin-1 (Cav-1) which are in cell membranes structures involved in carcinogenesis, in oral squamous cell carcinoma (OSCC) and oral lichen planus (OLP) and compared them to controls. We also investigated their relationship to clinicopathological indices. In this case-control study, 29 paraffin blocks of OLP patients were compared to 29 paraffin blocks of OSCC samples as well as 28 paraffin blocks of normal oral tissue. Real-time quantitative PCR was performed to determine gene expressions and results were analyzed for their relationship to clinical data using chi-square, Kruskal-Wallis and Mann-Whitney tests. The mean age of OSCC and OLP patients were 59.24 ± 15.04 and 48.79 ± 14.17 years, respectively. The Cat-B and Cav-1 expressions were significantly higher in OSCC and OLP samples compared to control (p < 0.001). The highest expression was found in OSCC samples. The difference between OLP and control samples for Cat-B and Cav-1 expression was significant. There was no association between the gene expression and age, gender, duration of disease, Thongprasom score, smoking and cutaneous lichen planus. However, the expressions were related to the grade and stage of OSCC samples (P = 0.01, P = 0.02). The gene expressions of Cat-B and Cav-1 in OSCC were associated with the stage and grade of lesions. Therefore, they appear to be useful in predicting the biological behavior of OSCC and malignant transformation of OLP, although this process is multi factorial and more investigations are needed.

Pakfetrat A ，Delavarian Z ，Mohtasham N ，Mohajer Tehran F ，Samiee N ... -  《-》

Bmi1 expression in oral lichen planus and the risk of progression to oral squamous cell carcinoma.

Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk of progression to oral squamous cell carcinoma (OSCC). The objective of this study was to determine protein expression of cancer stem cell factor Bmi1 in a longitudinal series of patients with OLP and evaluate the correlation between Bmi1 expression and the risk of progression to OSCC. In a retrospective study, Bmi1 expression was determined using immunohistochemistry in samples from 96 patients with OLP who received a mean follow-up of 54 months, including patients who did not progress to OSCC (n=87) and patients who had progressed to OSCC (n=9). Analysis of 10 cases of normal oral mucosa and 6 cases of postmalignant OSCC form previously diagnosed OLP was also performed. The results showed that Bmi1 expression was observed in 32 (36.8%) of 87 cases of nonprogressing OLP and in 8 (88.9%) of 9 cases of progressing OLP. Bmi1 was not expressed in normal oral mucosa, but it was positively expressed in the 6 (100%) cases of OSCC. Multivariate analysis revealed that the risk of malignant progression in the patients with Bmi1-positive expression was significantly higher than those with Bmi1 negativity (odds ratio, 20.75; 95% confidence interval, 2.21-194.57; P=.008). Collectively, Bmi1 expression was significantly associated with malignant transformation in a large series of patients with OLP who received a longitudinal observation. Our findings suggested that Bmi1 may serve as a useful marker for the identification of a high risk of malignant progression of OLP.

Ma L ，Wang H ，Yao H ，Zhu L ，Liu W ，Zhou Z ... -  《-》

CD133 expression in oral lichen planus correlated with the risk for progression to oral squamous cell carcinoma.

Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk for progression to oral squamous cell carcinoma (OSCC). The objective of this study to determine protein expression of cancer stem cell marker CD133 in tissue samples of patients with OLP and evaluate the correlation between CD133 expression and the risk of progression to OSCC. In this longitudinal case-control study, a total of 110 patients with OLP who received a mean follow-up of 56 months were enrolled, including 100 patients who did not progress to OSCC and 10 patients who had progressed to OSCC. CD133 expression was determined using immunohistochemistry in samples from these patients. Analysis of 10 cases of normal oral mucosa and 6 cases of postmalignant OSCC form previously diagnosed OLP was also performed. The results showed that CD133 expression was observed in 29% cases of nonprogressing OLP and in 80% cases of progressing OLP (P = .002). CD133 was not expressed in normal oral mucosa, but it positively expressed in the 100% cases of OSCC. Logistic regression analysis revealed that the risk of malignant progression in the patients with CD133-positive expression was significantly higher than those with CD133 negativity (odds ratio, 9.79; 95% confidence interval, 1.96-48.92; P = .005). Collectively, CD133 expression was significantly associated with malignant progression in a longitudinal series of patients with OLP. Our findings suggested that CD133 may serve as a novel candidate biomarker for risk assessment of malignant potential of OLP.

Sun L ，Feng J ，Ma L ，Liu W ，Zhou Z ... -  《-》

Metabolic changes during malignant transformation in primary cells of oral lichen planus: Succinate accumulation and tumour suppression.

Oral squamous cell carcinoma (OSCC) is usually diagnosed at late stages, which leads to high morbidity. There are evidence that chronic inflammation (eg oral lichen planus [OLP]) was a risk factor of OSCC, but often misdiagnosed or ignored until invasion and metastasis. By applying precision medicine, the molecular microenvironment variations and relevant biomarkers for the malignant transformation from OLP to OSCC can be fully investigated. Several studies pointed out that the metabolic pathway were suppressed in OSCC. However, it remains unclear how the systemic profile of the metabolites change during the malignant transformation. In this study, we examined and compared the mucosa samples from 11 healthy individuals, 10 OLP patients and 21 OSCC patients. Based on the results, succinate, a key metabolite of the tricarboxylic acid cycle pathway, was accumulated in the primary cultured precancerous OLP keratinocytes and OSCC cells. Then, we found that succinate activated the hypoxia-inducible factor-1 alpha (HIF-1α) pathway and induced apoptosis, which could also be up-regulated by the tumour suppressor lncRNA MEG3. These results suggested the critical roles of succinate and MEG3 in the metabolic changes during malignant transformation from OLP to OSCC, which indicated that succinate, HIF1α and downstream proteins might serve as new biomarkers of precancerous OLP for early diagnosis and therapeutic monitoring. In addition, succinate or its prodrugs might become a potential therapy for the prevention or treatment of OSCC.

Yang Q ，Sun H ，Wang X ，Yu X ，Zhang J ，Guo B ，Hexige S ... -  《-》