Malignant Transformation Of Oral Mucosa Research Articles

Life-time tobacco consumption and oral cancer among citizens of a high incidence metropolis.

To analyse dose-response relationship between the common risk factor of tobacco consumption and oral lesions like squamous cell carcinoma and pre-cancerous lesions. The cross-sectional case-control study was conducted at Ziauddin University, Karachi from 2011 to 2016, and comprised histologically-confirmed cases of oral squamous cell carcinoma in group A, clinically-diagnosed oral pre-cancerous lesions in group B, and habit-matched controls in group C. The subjects were enrolled from 2011 to 2016. Life-time tobacco exposure was calculated using chewing index and smoking index for comparison between cases and controls. Data was analysed using SPSS 20. Of the 358 subjects, 150(42%) were in group A with a mean age of 47.1±12.22 years, 100(28%) were in group B with a mean age of 34.17±13.78 years, and 108(30%) were in group C with a mean age of 41.6±14.58 years. Of all the group A patients, 125(83.33%) and 96(96%) in group B had a positive history of tobacco use, with tobacco-chewers being the most in numbers 172(68.8%). Exclusive smoking was seen in 11(4.4%) cases, 38(15.2%) patients were both tobacco-chewers and smokers, and 29(11.6%) were tobacco-free. Group A and B patients had life-time tobacco exposures either equal or lower compared to group C controls (p>0.05). Life-time tobacco exposure indices were either comparable or lower in patients compared to the controls.

Research progress of Candida albicans on malignant transformation of oral mucosal diseases

Oral cancer is the most common malignant tumor in the head and neck, and is one of the world's top ten malignancies. Microbial infection is an important risk factor of oral cancer. Candida albicans is the most popular opportunistic fungal pathogen. Epidemiological studies have shown that Candida albicans is closely tied to oral malignancy. Animal experimentation have also proven that infection of Candida albicans can promote the development of oral epithelial carcinogenesis. The current studies have revealed several mechanisms involved in this process, including destroying the epithelial barrier, producing carcinogenic substances (nitrosamines, acetaldehyde), inducing chronic inflammation, activating immune response, etc. However, current researches on mechanisms are still inadequate, and some hypotheses remain controversial. Here, we review the findings related to Candida albicans' effect on the malignant transformation of oral mucosa, hoping to provide reference for deep research and controlling oral cancer clinically.

Mesenchymal stem cells participate in oral mucosa carcinogenesis by regulating T cell proliferation

Recent evidences suggested that Mesenchymal stem cells (MSCs) may be involved in tumor formation by modulating of the tumor microenvironment, but it is still unclear the potential of MSCs in the malignant transformation of oral mucosa. Using a chemically-induced oral carcinogenesis model by 4-nitroquinoline-1-oxide (4NQO), we generated precancerous lesions and cancerous lesions in the oral cavity of rats. Flow cytometric analysis on lesions derived single cell suspension revealed an increase in the proportion of MSCs and a decreased proportion of T cell during oral mucosa malignancy. Moreover, MSCs showed increased immunosuppression capacity on T cell proliferation during mucosa malignancy. At last, we demonstrated that higher frequency of lesions resident MSCs was correlated with more Ki67 expression in the lesion, which indicated higher cellular proliferative status in the lesions. Our study demonstrated that MSCs may play an important role in oral mucosa malignant transformation through regulating T cell proliferation.

Blockade of PD-1 effectively inhibits in vivo malignant transformation of oral mucosa

ABSTRACTCurbing PD-1 immunosuppressive signaling represents an effective immune awakening or immune-reactivation approach for tumor eradication for many cancers. Yet, the potential involvement of this critical PD-1 immunosuppressive signaling in de novo malignant transformation of epithelial cells to pre-cancerous or cancerous lesions is largely unknown. In this study, we demonstrate that PD-1 signaling is critically involved in de novo malignant transformation of oral mucosa upon carcinogen exposure in vivo. Our findings revealed that 4NQO-treated mice had almost double the numbers of PD-1-positive CD4+ cells and PD-1-positive CD8+ cells in peripheral blood lymphocytes as well as elevated PD-1 expression in tumor infiltrating lymphocytes (when compared to that of control-treated mice), strongly supportive of a general immune-suppression induced by carcinogen challenges in vivo. Importantly, inhibition of PD-1 signaling during the carcinogenesis process (immediately after 4NQO challenge) significantly reduced and delayed de novo formation of both pre-cancerous and cancerous lesions in vivo, in conjunction with effective PD-1 down-modulation in the tumor infiltrating leukocyte and peripheral lymph organs. Lastly, reduction of carcinogen-induced lesions upon PD-1 mAb treatment in vivo was accompanied by reduction of potent immunosuppressive myeloid-derived suppressor cells (MDSCs), and increase in “activated” T cell accumulations in the lesion-microenvironment (127% increase) and peripheral lymph nodes (25% increase). These data support PD-1 blockade as a new approach to enhance the efficacy of T-cell immunotherapy and reduce canceration rate in premalignant lesions.

P53 immunohistochemical staining patterns in oral squamous cell carcinoma

Background: Mutation of p53 gene is one of the most common events in oral carcinogenesis. Accumulation of p53 protein has also been detected in premalignant lesions.Materials and Methods: This study included 40 biopsy samples, which were received in department of pathology, Sarojini Naidu Medical College, Agra, to ascertain p53 expression by immunohistochemically, in patients with oral squamous cell carcinomas and to correlate its expression with histological grade, different sites in oral cavity and tobacco intake/smoking habits.Results: Out of 40 biopsies of oral mucosa, 03 showed normal oral mucosa and 37 were diagnosed as squamous cell carcinoma (SCC), most patients were in 5th and 6th decade and majority (86.5%) of oral SCC were males with buccal mucosa being the most common site. There was a statistically significant difference in p53 expression between oral SCC and normal oral mucosa (p value <0.05). Of total 37 cases, 12 cases were well differentiated type, 16 moderately differentiated and 09 of poorly differentiated type of SCC. In each category, about two thirds were positive for p53 staining. Out of total 37 cases of oral SCC, 64.9% were positive and 35.1% were negative for p53 expression, 34 cases had positive history of tobacco intake/smoking habits, of which 23 cases were positive while 11 cases were negative for p53 staining.Conclusion: Abnormal p53 protein was detected in 64.9% of oral squamous cell carcinoma, but not in normal oral mucosa. p53 expression was associated with malignant transformation of oral mucosa.

Assessment of c-Jun, c-Fos and cyclin D1 in premalignant and malignant oral lesions

Some oral cancers are known to develop from dysplastic oral epithelium. In the present study, the expression of c-Jun, c-Fos, and cyclin D1 proteins in oral epithelial lesions with different degrees of dysplasia, and in oral squamous cell carcinomas (OSCCs) was evaluated. Eighteen cases of mild dysplasia, 23 cases of moderate to severe dysplasia and 24 OSCCs were studied immunohistochemically. Additionally, 15 sections of oral mucosa without any evidence of dysplasia were included in the study. c-Jun expression increased according to the degree of oral dysplasia, with the greatest expression found in OSCC. c-Fos expression was intense in normal mucosa, reduced in mild dysplasia and high in moderate to severe dysplasia and in OSCCs. Cyclin D1 was expressed in only a few cases of moderate to severe dysplasia and in most of the OSCCs. Statistical analysis showed a correlation between the three proteins and the degree of epithelial alteration. The present results indicate a possible role of c-Jun and c-Fos in malignant transformation of oral mucosa.

Ultrastructural changes in malignant transformation of oral mucosa

Transmission electron microscopy (EM) has been used to identify the ultrastructural details of normal and cancerous human oral mucosa. However, inconsistent reports of structural descriptions have rendered transmission EM valueless in the diagnosis of oral squamous cell carcinoma (SCC) or as a prognostic indicator. To identify features of dysplasia for diagnostic purposes, normal mucosa, severe dysplasia, oral SCC and normal margin adjacent to oral SCC were used to compare the ultrastructural features of normal and premalignant oral mucosa and oral SCC. The preparatory stages of dehydration, embedding, cutting and positive staining for transmission EM were modified and tested to improve ultrastructural definition. Thin and discontinuous basal laminas were found in mucosa with severe dysplasia and normal margin adjacent to oral SCC. No basal lamina was identified in oral SCC. This study has shown that there are some ultrastructural changes during malignant transformation of oral mucosa. Together with other laboratory investigative techniques, transmission EM may be helpful in detecting malignant changes in oral mucosa.

Assessment of p53 and Ki-67 expression in snuff induced lesions

An immunohistochemical study of snuff-induced lesions with a monoclonal antibody (DO-7) specific to p53 mutant and wildtype antioncogene product demonstrated nuclear overexpression of the mutant protein in 45.9 nuclear profiles/mm 2 epithelium (SEM 10.8; n = 15) compared with only 0.18 positively stained nuclear profiles/mm 2 in the control group (SEM 0.18; n = 4). Furthermore, the biopsy material was also stained with the antibody Ki-67, which has been shown to be excellent for the estimation of the growth fraction in both normal and malignant human tissues. Ki-67 stained positive in 566.1 nuclear profiles/mm 2 epithelium (SEM 85.0; n = 15) in the snuff group compared with 20.2 nuclear profiles/mm 2 (SEM 4.9; n = 4) in the control group. To the best of our knowledge, this is the first study showing overexpression of p53 protein and Ki-67 in snuff-induced lesions. The results may indicate that the p53 gene is involved in the initial events leading to subsequent malignant transformation of oral mucosa exposed to snuff. Furthermore, mutations of the p53 gene have been associated with increased cellular proliferation with greater risk of perpetuation of mutations and malignant transformation.

Studies on Trace Elements in Progressive Pathology of DMBA-Induced Hamster Buccal Pouch Carcinogenesis.

Alterations in the levels of copper, zinc, and cadmium were investigated in both serum and buccal mucosa of hamsters in progressive pathology, namely, hyperplasia, papilloma, early invasive carcinoma, and well-differentiated squamous cell carcinoma. Hamster buccal pouch carcinogenesis was induced by tri-weekly topical application of a 0.5% solution of 7, 12-dimethylbenz(a)anthracene (DMBA) in liquid paraffin applied with a brush on the right buccal mucosa for 16 weeks. Serum copper levels and the copper/zinc ratio were generally elevated, and serum zinc levels were generally depressed, during carcinogenesis; and these alterations were related to the advancing stages of carcinogenesis. In transformed buccal mucosa, a significant decrease in the level of copper and a significant increase in the level of zinc were seen with papillomatous tissues onwards, and the alterations were progressive with the development of carcinomas. The changes in the levels of cadmium were moderate and occurred only in carcinomas. These data suggest that the alterations in the levels of copper, zinc, and copper/zinc ratio may be used as markers for pathological changes in the malignant transformation of oral mucosa.

Differential lectin‐bindings in normal and precancerous epithelium and squamous cell carcinoma of the oral mucosa

In order to establish a useful and objective marker of malignancy of oral mucosa, the binding sites for Ulex europaeus agglutinin I (UEA-I). Bandeiraea simplicifolia agglutinin I (BSA-I) and peanut agglutinin (PNA) were comparatively examined in the surgical materials from the normal, dysplastic and cancerous epithelium of the oral mucosa by a novel lectin-antilectin immunoperoxidase method. Based on the staining patterns of the normal keratinized epithelium, UEA-I was regarded as the marker for the prickle cells, BSA-I for the cells in the upper prickle to the horny layers, and PNA for those in the basal layer. As the degree of dysplasia advanced, all layers of epithelium came to react with UEA-I and PNA, whereas the BSA-I binding was negative. Positive reactions for UEA-I and PNA were seen in most carcinoma cells other than the keratinizing foci stained by BSA-I. The results indicate that a UEA-I-positive reaction in the basal cells, a PNA-positive in the prickle cells and loss of receptor for BSA-I occur in the course of malignant transformation of oral mucosa, and that these lectins may be regarded as useful markers of oral epithelial cytoplasmic differentiation.