Premalignant Oral Epithelial Lesions Research Articles

The role of altered microRNAexpression in premalignant and malignant head and neck lesions with epithelial origin.

The premalignant lesions of the oral cavity carry a risk of transformation to malignancy. Hence, early diagnosis followed by timely intervention remarkably affects the prognosis of patients. During tumorigenesis, particular microRNAs (miRNAs) show altered expressions and because of their post transcriptionally regulatory role could provide favorable diagnostic, therapeutic, or prognostic values in head and neck cancers. In this review, we have demonstrated diagnostic, prognostic, and potential therapeutic roles of some miRNAs associated with oral premalignant and malignant lesions based on previous validate studies. It is previously documented that dysregulation of miRNAs contributes to cancer development and progression. MiRNAscould be tumor suppressors that normally suppress cell proliferation, differentiation, and apoptosis or play as oncogenes that improved tumorigenesis process. Altered expression of miRNAs has also been reported in premalignant oral epithelial lesions such as leukoplakia, oral submucous fibrosis, oral lichen planus and some malignant carcinoma like oral squamous cell, verrucous, spindle cell, Merkel cell carcinoma and basal cell. Some of miRNAs could be new therapeutic candidates in miRNA-based target gene therapy. Although more investigations are required to identify the most favorable miRNA candidate, altered expression of some miRNAs could be used as biomarkers in premalignant lesions and oral cancers with high sensitivity and specificity.

Comparative study of effectiveness of colposcopic examination versus visual examination for determining the biopsy site of potentially premalignant oral epithelial lesions

Diagnosis of oral malignant and potentially premalignant oral epithelial lesions (PPOELs) cannot be based solely on clinical findings. Tissue biopsy with histopathologic examination remains the gold standard in diagnosis. Selection of a representative biopsy site becomes essential to arrive at an early and precise diagnosis which substantially reduces the incidence of morbidity and mortality from oral cancer. The site for biopsy, however, is always a subjective choice that sometimes raises doubts about its representativeness. Among various techniques developed to complement clinical examination and facilitate early diagnosis, colposcopy can be a simple, reliable diagnostic method available for the selection of the most appropriate biopsy site based on the vascular patterns. Hence, this study has been planned to assess the role of colposcopic examination in the selection of the most representative specimen for histopathologic examination from the oral lesions.

Metallothioneins and Megalin Expression Profiling in Premalignant and Malignant Oral Squamous Epithelial Lesions.

Simple SummaryInteractions of metallothioneins with the multiligand receptor megalin have been found to promote cell survival and proliferation after noxious stimuli in non-malignant tissues. However, the relationship between these proteins and their interaction remains to be addressed in malignancies and premalignant lesions. In this retrospective study, we compared the expression profiles of metallothioneins and megalin in different histological grades of oral squamous cell carcinoma, oral leukoplakia, and oral lichen planus. The data obtained show a gradual increase of both proteins concomitantly with the gaining of more malignant features, as well as their co-expression and direct interaction in carcinomatous tissue. The results point to the pro-oncogenic role of the metallothionein-megalin functional axis, which may impact tumor phenotype and behavior.This study aimed to assess the relationship and possible interactions between metallothioneins (MTs) and megalin (LRP-2) in different grades of oral squamous cell carcinoma (OSCC) and premalignant lesions of the oral mucosa (oral leukoplakia and oral lichen planus). The study included archived samples of 114 patients and control subjects. Protein expression was examined by immunohistochemistry and immunofluorescence, and staining quantification was performed by ImageJ software. Protein interaction in cancer tissue was tested and visualized by proximity ligation assay. Mann-Whitney and Kruskal-Wallis tests were used to determine the significance of differences between each group, whereas Pearson correlation coefficient was performed to test correlation. Expression of both proteins differed significantly between each group showing the same pattern of gradual increasing from oral lichen planus to poorly differentiated OSCC. Moreover, MTs and megalin were found to co-express and interact in cancer tissue, and their expression positively correlated within the overall study group. Findings of prominent nuclear and chromosomal megalin expression suggest that it undergoes regulated intramembrane proteolysis upon MTs binding, indicating its ability to directly affect gene expression and cellular division in cancer tissue. The data obtained point to the onco-driving potential of MTs-megalin interaction.

A Review of CO2 Laser-Mediated Therapy for Oral Mucosal Lesions

(1) Background: Several studies investigating the clinical outcomes of potentially premalignant oral epithelial lesions treated with CO2 lasers have been published over the last decades. (2) Methods: A systematic research review was performed for studies published between 2011 and 2021 in the PubMed, Science Direct, and Google Scholar databases. (3) Results: Initially, the search identified 52 relevant articles. The primary analysis of the titles and abstracts eliminated 22 articles, leaving 30 articles whose full texts were examined. A total of 22 articles met the inclusion criteria. The studies were classified into 3 categories. (4) Conclusions: After evaluating the results of all the studies included in this review, an initial general statement can be made, namely that CO2 lasers are a treatment option worth taking into consideration when approaching oral mucosal lesions. When compared to other types of lasers used in dental practice, the CO2 laser stands out due to its many advantages.

Long non‑coding RNAs are novel players in oral inflammatory disorders, potentially premalignant oral epitheliallesions and oral squamous cell carcinoma (Review).

In recent years, a large number of studies have shown that the abnormal expression of long non-coding (lnc)RNAs can lead to a variety of different diseases, including inflammatory disorders, cardiovascular disease, nervous system diseases, and cancers. Recent research has demonstrated the biological characteristics of lncRNAs and the important functions of lncRNAs in oral inflammation, precancerous lesions and cancers. present review aims to explore and discuss the potential roles of candidate lncRNAs in oral diseases by summarizing multiple lncRNA profiles in diseased and healthy oral tissues to deter-mine the altered lncRNA signatures. In addition, to highlight the exact regulatory mechanism of lncRNAs in oral inflammatory disorders, potentially premalignant oral epithelial lesions and oral squamous cell carcinoma. The detection of lncRNAs in oral samples has the potential to be used as a diagnostic and an early detection tool for oral diseases. Furthermore, lncRNAs are promising future therapeutic targets in oral diseases, and research in this field may expand in the future.

Well-armed is well started: A population-based study to assess risk stratification in potentially premalignant oral epithelial lesions.

Background:The association between potentially premalignant oral epithelial lesions (PPOEL), oral squamous cell carcinoma and its higher incidence in South-East Asian population due to the use of arecanut, pan, slaked lime and tobacco is well known. The study was carried out in urban and rural population of Bengaluru, Karnataka, to assess and correlate the pattern of habit, clinical presentation and cytological grading of PPOELs, attempting at identifying the main arms associated with risk of malignant transformation.Aims:Assessment of history, clinical presentation of PPOELs, co-relate with cytological grades and escalate to binary risk assessment.Materials and Methods:One hundred and fourteen cytological smears received at the Department from screening camps were stained with Papanicolaou and hematoxylin-eosin stains and correlated with the clinical data.Results/Statistics:Descriptive and inferential statistics were performed. 38% lie between 21 and 30 years, 76.3% males, 81 cases involved buccal mucosa with 51.1% Grade II cytosmear, 53.5% chewing tobacco habit, 10 cases involved multiple sites with 60% Grade II cytosmear and 6 cases showed Grade III cytosmear. Based on clinical risk factors and cytological grading, 15.3% were grouped under high risk lesions as against 5.4% when only cytological grading was considered.Conclusion:The incidence of PPOELs is increasing in young males with chewing tobacco mainly in buccal mucosa associated with habit. Biopsy and definitive treatment is necessary when the lesions are red, nonhomogeneous, seen in multiple sites and concomitant lesions with higher grades of dysplasia. The use of cytosmears in screening camps helps to assess, affirm and stress on biopsy on higher dysplasia grades as biopsy is not an acceptable norm in camps.

"SKILL TO KILL" - Oral cancer and potentially premalignant oral epithelial lesions (PPOELs): A survey approach. Emerging of a new system and professionals.

Background:Oral cancer is said to be the 6th most common cancer in men and 12th in women. Potentially malignant disorders/potentially premalignant oral epithelial lesion (PMDs/PPOELs) have shown an increased risk of progressing to cancer. In this regard, lack of awareness about identification of oral PMDs among healthcare providers in general and oral pathologists in particular is said to be responsible for the diagnostic delay. Oral cancer is said to be the most common cancer in men and 3rd most common in women in the Indian subcontinent. PMDs have shown an increased risk of progressing to cancer. The various rates of conversion include 14%–51% for erythroplakia, 60%–100% for proliferative verrucous leukoplakia and 7%–26% for oral submucous fibrosis (OSMF). In this regard, early detection at PPOEL level will lead to prevention of malignant transformation.Aims and Objectives:The purpose of this survey was: 1. To determine if awareness among professionals is essential/key to challenge the progression of PMDs of the oral cavity. 2. To examine and/ordiscern if oral pathologists felt enough was being done to address the issue of early detection and prevention and how the scenario could be improved further.Materials and Methods:A survey was designed to assess the interest, zeal, knowledge and skill of healthcare providers in general and oral pathologists in particular in careful examination of the oral cavity and early detection of PMDs. A questionnaire with 18 questions was designed to address these issues/points and distributed among post-graduate students and practicing oral pathologists on online platforms.Results:The results of the esurvey were collected, analyzed and the results discussed question wise. The validity and reliability of the questionnaire was assessed and confirmed with Aiken's index for validity and Cronbach's alpha for reliability. Inferential statistical analysis was performed using Chi square test with P = 0.05 being statistically significant.Conclusion:On evaluation of the survey, we found that 85% of the surveyees are on agreement that PPOELs should be registered in a standard format and should be included in the list of recognizable diseases. 89.2% and 87.8% of the respondents would like to be part of an active body for early detection and diagnosis and for Cancer screening in our country respectively. In conclusion, the oral pathology fraternity is eager to work for and tackle these PPOELs head on, provided the right opportunities and training are meted out to them.

Cortactin and focal adhesion kinase as predictors of cancer risk in patients with premalignant oral epithelial lesions

There is a need for novel and accurate biomarkers based on genetic abnormalities capable of predicting the risk of malignant transformation of epithelial lesions of the oral cavity. Therefore, we investigate the role of cortactin and focal adhesion kinase (FAK) protein expression in oral dysplasias and their potential utility as cancer risk markers. Cortactin and FAK expression were immunohistochemically evaluated in 64 patients with oral epithelial dysplasia. During follow-up, 17 of 64 patients developed an oral squamous cell carcinoma (OSCC). Increased immunoexpression of cortactin and FAK was found in 52 and 27 of 64 oral dysplasias, respectively, and the expression of both proteins increased with the grade of dysplasia. Increased cortactin and FAK expression was also observed in 13 and 15 OSCC, respectively. Overall, cortactin and FAK expression was maintained or further augmented in the oral squamous cell carcinoma compared to the patient-matched preinvasive lesion. Univariate analysis showed that cortactin and FAK expression, as well as histological grading were significantly associated with oral cancer risk. Strong coexpression of both proteins reflected a significantly higher cancer risk than that of weak to moderate expression or than whenever only one of those proteins showed a strong expression. In multivariate analysis, premalignant oral lesions which exhibited a high coexpression of cortactin and FAK showed a significant risk of developing an OSCC (HR=6.298). Our results indicate that strong immunoexpression of cortactin and FAK, and not only one of them, is a predicting factor for increased cancer risk in oral premalignant lesions.

Poster 022: Pharmacokinetic Analyses of Chemopreventive Bioadhesive Berry Gel in Humans

Early diagnosis and management of premalignant oral epithelial lesions is the optimal strategy to decrease oral squamous cell carcinoma (OSCC) morbidity and mortality. Chemoprevention, the prevention, inhibition or reversal of malignant transformation by intervention with chemically derived or naturally occurring dietary substances, is a promising treatment approach.

Increased expression of inducible nitric oxide synthase for human oral submucous fibrosis, verrucous hyperplasia, and verrucous carcinoma

Abstract.Three isoforms of nitric oxide synthase (NOS), endothelial, neuronal and inducible NOS (iNOS), have been identified in humans. Enhanced expression of iNOS protein has been previously reported for human oral epithelial dysplasias, a human oral premalignant epithelial lesion; however, this expression has not been demonstrated for other premalignant epithelial lesions, namely, oral submucous fibrosis (SF) and verrucous hyperplasia (VH). On the other hand, iNOS protein expression has not been reported in human oral verrucous carcinoma (VCa). The aim of this current study was to determine whether iNOS protein also occurs for oral SF, VH and VCa lesions. We found that membranous stainings were observed chiefly in oral SF lesions (17/20, 85%), whereas cytoplasmic stainings were mainly found in the VH variants (16/20, 80%). By contrast, cytoplasmic and/or nuclear stainings were observed in the specimens of verrucous carcinoma (17/20, 85%). Since no iNOS activity could be detected for any of our specimens of normal buccal mucosa in the present immunohistochemical study, this suggests that an NOS-dependent mechanism may be involved in the malignant transformation of these two premalignant oral epithelial lesions.

Quantitation of epidermal growth factor receptor gene amplification by competitive polymerase chain reaction in pre-malignant and malignant oral epithelial lesions.

Abnormal amplification of epidermal growth factor receptor (EGFR) gene has been reported widely in various human tumors. However, the status of amplification of this gene in the process of carcinogenesis is not clearly defined. We used competitive polymerase chain reaction (PCR) to study whether EGFR gene is amplified and the degree of amplification in pre-malignant and malignant oral epithelial lesions, and also examined the relationship between EGFR gene aberration and the development of squamous cell carcinoma (SCC). Genomic DNA was extracted from paraffin sections of 17 cases of oral epithelial dysplasia (ED), four cases of carcinoma in situ (CIS), and 20 cases of untreated primary SCC. The extracted DNA was subjected to competitive PCR to amplify EGFR gene. Amplification of the EGFR gene was observed in three cases (17%) of ED, one case of CIS and four cases (20%) of SCC. In cases showing EGFR gene amplification, the degree of amplification was low in ED and CIS cases, whereas it was extremely high in SCC cases. These results suggest that amplification of EGFR gene occurs in the relatively early stage of the development of oral SCC. However, a high level of EGFR gene accumulation probably plays an important role in the progression to invasive cancer.

Cell cycle proteins and the development of oral squamous cell carcinoma.

Expression of cell cycle regulatory proteins was evaluated in premalignant and malignant oral epithelial lesions, to test the hypothesis that protein regulation of the cell cycle may be altered in the development of oral squamous cell carcinoma. Archived paraffin-embedded specimens (n = 90) from 25 patients with recurrent or persistent lesions were evaluated in immunohistochemically stained sections for cell cycle regulatory proteins p53, Rb, Cyclin D1, p27, and p21. The cell cycle was also evaluated by expression of nuclear protein Ki 67. Sections were graded semiquantitatively using a 0-3 + scale to indicate the percentage of positively stained cells. The initial histologic diagnosis for 17/25 patients was either focal keratosis, mild dysplasia, or moderate dysplasia; the initial diagnosis for the remaining eight patients ranged from severe dysplasia to moderately differentiated squamous cell carcinoma. Thirty-three of 90 specimens showed positive p53 expression, 11 of which were dysplasias. Eighty-nine of 90 specimens, from all stages of disease, showed positive Rb expression. Twenty-three of 90 specimens showed positive Cyclin D1 expression, typically in the later stages (carcinoma) of a patient's disease. Eighty-four of 90 specimens showed positive p21 expression; while 55 of 90 specimens were positive for p27. In control mucosa, p27 was highly expressed, while Rb and p21 proteins were expressed at relatively low levels; p53 and Cyclin D1 proteins were largely absent. Generally, staining of p53, Rb, p21, and Ki 67 increased with time in serial biopsies, while p27 showed decreased staining with disease progression. These data show that cell cycle regulatory proteins are altered in both premalignant and malignant disease, and that protein phenotypes are heterogeneous. P53 expression is seen early, and Cyclin D1 expression is seen late in the development of oral premalignant and malignant disease. Expression of p53, Rb, p21 and Ki67 increased, while p27 decreased, with disease progression.

Apoptosis-associated proteins and the development of oral squamous cell carcinoma.

Expression of apoptosis-associated proteins was evaluated in premalignant and malignant oral epithelial lesions, to test the hypothesis that protein regulation of apoptosis may be altered in the development of oral squamous cell carcinoma. Ninety archived paraffin-embedded specimens from 25 patients (two or more sequential biopsies each) and eight control specimens were evaluated in immunohistochemically stained sections for tumor suppressor protein p53, p53 binding protein mdm-2, and apoptosis regulatory proteins Bcl-2, Bcl-X, Bax, and Bak. The initial histologic diagnosis for 17/25 patients was either focal keratosis, mild dysplasia, or moderate dysplasia; the initial diagnosis for the remaining eight patients ranged from severe dysplasia to moderately differentiated squamous cell carcinoma. Thirty of 90 specimens showed positive p53 expression, nine of which were dysplasias. In patients with one or more lesions displaying p53 expression, there was increased intensity of staining with disease progression. Bak was expressed in 57/90 specimens, including 27 dysplasias of various grades. There was also a significantly increased intensity of Bak staining with disease progression, which did not appear to be dependent upon p53 status. Bcl-X was expressed in 73/90 specimens, with staining displayed earlier in premalignant lesions than either p53 or Bak. Ten of 90 specimens were positive for Bcl-2 (all were dysplasias or carcinomas), and only 2/90 specimens were positive for Bax. Eleven of 90 specimens were positive for mdm-2; six of which were also positive for p53. These data show that apoptosis-associated proteins are altered in variable patterns in both premalignant and malignant oral epithelial lesions. p53 and especially Bak and Bcl-X are expressed early; Bax is largely absent; and Bcl-2 and mdm-2 show sporadic expression in the development of oral premalignant and malignant disease.

CD44 variant 6 (CD44v6) expression as a progression marker in benign, premalignant and malignant oral epithelial tissues

The change in the expression pattern of CD44 variant 6 (CD44v6) protein in benign, premalignant, and malignant (SCC) oral epithelial lesions was studied immunohistochemically and compared with the pattern in normal mucosa in order to examine whether this gene can serve as a progression marker in patients with SCC. The principal finding is that CD44v6 expression was clearly downregulated in most cases of severe premalignant lesions as well as in most of the SCCs. The staining pattern and intensity varied according to the degree of dysplasia and to the degree of differentiation of the SCCs. Premalignant severe epithelial dysplasia cases with early features of invasion, not yet developed into SCC, showed distinctly downregulated expression of CD44v6 protein whereas hyperplastic and benign epithelial lesions (papilloma) expressed positive staining patterns comparable to those of the normal counterparts. The authors conclude that alteration in CD44v6 may occur as an early event in primary oral SCC development, as well as in premalignant severe epithelial dysplasia. It can thus, be used as a molecular progression marker when screening for oral cancer.