Degree Of Epithelial Dysplasia Research Articles

Molecular Docking to Predict a Novel Bioactive Compound as an Inhibitor of Beta Catenin in Oral Squamous Cell Carcinoma

Background: Efforts aimed at enhancing patient survival have focused on early detection and diagnosis, followed by prompt treatment of potentially malignant disorders, aiming to halt their advancement into oral cancer. Recent research has shed light on the pivotal role of the Wnt/B-catenin signaling pathway in the pathogenesis of potentially malignant oral conditions. This pathway undergoes a progressive activation process across various degrees of epithelial dysplasia, including mild, moderate, and severe dysplasia. Beta-catenin (B-catenin) triggers the activation of genes associated with crucial cellular processes, which include cell growth, viability, differentiation, and migration. Aims: In the present study, we aimed to design a novel drug with 3 bioactive compounds through insilico analysis, assess its efficacy against B-catenin, and develop a new pharmacophore with an emphasis on B-catenin inhibition. Materials and Methods: Based on prior literature, three molecules possessing potent beta-cateninblocking properties were selected, namely rosmarinic acid, zosterin, and stigmasterol. To evaluate their binding affinities, molecular docking studies were conducted using the Lamarckian Genetic Algorithm implemented in AutoDock Tools 1.5.7. Initially, AutoGrid was employed to construct a grid box for docking purposes. The estimated binding poses of each compound were subjected to clustering analysis. The interactions between the compounds and beta-catenin were visualized and explored using PyMOL software. Results: Stigmasterol displayed the most substantial binding energy with a value of -3.86 kcal/mol, followed by rosmarinic acid and zosterin. Conclusion: Bioactive components can be used for beta-catenin pathway blocking. Future research should be carried out to assess these substances in more clinically relevant cancer models.

White lesions of the oral mucosa: leukoplakia

White lesions of the oral mucosa may be caused by various disorders. In most instances of white lesions, diagnoses can be made solely on clinical grounds. When the clinical diagnosis is not compatible with a known disease, the term leukoplakia is used. This is of importance since the yearly malignant transformation rate of oral leukoplakia into a squamous cell carcinoma is 2-4%. The presence and degree of epithelial dysplasia is the most important predictor for malignant transformation.

Clinicopathological Analysis of Actinic Cheilitis: A Systematic Review with Meta-analyses.

This systematic review aimed to conduct a complete investigation of the demographic aspects, clinicopathological features, degrees of epithelial dysplasia, and malignant transformation rate of actinic cheilitis. The study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the International Prospective Register of Systematic Reviews (CRD42020201254). A search without year and language restrictions was performed using PubMed/MEDLINE, Embase, Virtual Health Library, Scopus, Web of Science, and gray literature. Studies that provided information on patients with actinic cheilitis were included, excluding those with general information on other diseases or other types of cheilitis. Risk of bias was explored using the Joanna Briggs Institute tool. Narrative and quantitative data syntheses were performed using meta-analyses and subgroup analyses. Association tests were also performed. Thirteen studies (728 patients) were included. The most prevalent clinical signs were dryness (99%), blurred demarcation between the lip vermilion and skin (82%), scaling (69%), and atrophy (69%). Regarding epithelial dysplasia, a prevalence of mild dysplasia (34.2%), followed by moderate (27.5%), and severe (14.9%). The malignant transformation rate was 14%. Crusts, ulcerations, and erythematous areas were associated with lip carcinoma (p < 0.001), and scaling was associated with actinic cheilitis (p < 0.001). This study revealed several features of actinic cheilitis, providing an overview of the disease. It is suggested that new studies help develop policy guides for the standardization of clinical criteria, enabling more rigorous and homogeneous analysis of actinic cheilitis.

Dysplastic crypts in asymmetric branching found in ulcerative colitis-associated dysplasia.

Biopsies from patients with ulcerative colitis (UC) often show crypt branching´s (CB). The purpose was to analyze the frequency of CB in biopsies with dysplasia in UC (D-UC). Digitalized-sections from 49 consecutive D-UC cases were reviewed and all CB were recorded. Potential confounders such as gender, age, UC-duration, localization in the colorectum, degree of epithelial dysplasia and number of mucosal samples/biopsy, were investigated. A total of 334 dysplastic CB (DCB) were recorded in the 49 D-UC cases; 321 (96.1%) DCB were in asymmetric branching (DCAB), and the remaining 13 (3.9%), in symmetric branching (DCSB). Out of the 49 D-UC cases, 41% had 1-4 DCAB, 43% 5-9 DCAB, 10% 10-15 DCAB, and the remaining 6%, ≥16 DCAB. Low-grade dysplasia (LGD) was present in 44 (90%) of the 49 D-UC cases, and high-grade dysplasia (HGD) in the remaining 5 (10%). The frequency of DCAB was not influenced by age, gender, biopsy site (right colon, left colon, or rectum), number of mucosal samples/biopsy, degree of dysplasia or UC duration. Two novel histologic phenotypes of DCB in UC-associated dysplasia are reported, namely DCAB and DCSB. The wide variation in DCAB-frequency in UC-associated dysplasia suggests potential biological differences between cases.

650O A phase II study of nivolumab for high-risk oral leukoplakia

Oral proliferative leukoplakia (PL) is an aggressive precancerous disease characterized by multifocal lesions and a high-risk of transformation to oral squamous cell carcinoma (OSCC). There are no effective therapies that prevent progression to oral cancer. PL demonstrates a rich immune microenvironment, providing strong rationale to evaluate PD-1 blockade as preventative immunotherapy. This single-arm, phase 2 trial investigated nivolumab (N) among patients (pts) with PL (multifocal, contiguous, or a single lesion ≥4 cm with any degree of epithelial dysplasia); a history of previously treated early-stage OSCC was permitted. Pts underwent pre-treatment biopsy of 1-3 sites then received 4 doses of N (480 mg IV) every 28-days, followed by re-biopsy. Intraoral photographs and bidirectional measurements occurred at each visit. Primary endpoint: change in composite score (size and degree of dysplasia) pre- to post-treatment (CR: >80% decrease in score; PR: 40-80% decrease; PD: ≥10% increase in composite score or new OSCC). Secondary endpoints: safety, cancer-free survival (CFS). Exploratory aims: PD-L1 status, genomic and immune profiling parameters. Between 1/2019 and 12/2021, 33 pts enrolled; 30 evaluable to date. Median age: 64 (range: 32-80), mostly women (18, 60%), 16 (53%) former/current smokers; oral tongue (13, 43%) was the main disease subsite; 8 (27%) had prior OSCC. A decrease of ≥40% in composite score was observed in 37% of pts (3 CRs and 8 PRs); 14 (47%) had stable disease, 4 experienced PD. 26 (86%) completed all 4 doses of N; 2 (7%) discontinued for toxicity, 2 (7%) for PD. Grade 3-4 irAEs were noted among 7 (23%) pts (hyperglycemia, colitis, hepatitis). At median follow-up of 16.3 mos (4.1-34.3+), median CFS was not reached, with 7 (23%) cancer events observed (3 among prior responders); 1-year CFS: 76.5% (95%CI 54.5-88.8). All pts are alive at last follow-up. Baseline median PD-L1 CPS trended higher among responders (15 vs. 5, p=0.10). Nivolumab yielded a best response of PL regression among 37% of pts with a favorable overall CFS. This is the first study to demonstrate evidence of efficacy using preventative immunotherapy for high-risk oral precancerous disease.

OXIDATIVE DNA DAMAGE IN ORAL LEUKOPLAKIA AND ITS ROLE IN THE ORAL CARCINOGENESIS

<h3>Objectives</h3> To evaluate oxidative DNA damage (8-hydroxy-2′-deoxyguanosine [8-OHdG]) and its repair by the base excision repair pathway (Redox factor-1 [Ref-1]; X-ray Repair Cross Complementing-1 [XRCC-1]) in oral leukoplakia (OL) with different degrees of epithelial dysplasia (ED). <h3>Study Design</h3> Forty-four cases of OL and 10 normal oral mucosa (NOM) were evaluated quantitatively for 8-OHdG, Ref-1, and XRCC-1 by immunohistochemistry. <h3>Results</h3> Cytoplasmic 8-OHdG expression was significantly associated with multiple synchronous lesions (<i>P</i> = .048). A significantly gradual cytoplasmic 8-OHdG increase was observed between NOM and ED (<i>P</i> < .05). Nuclear Ref-1 expression was significantly lower (<i>P</i> = .004) in nondysplasia/mild ED, whereas its cytoplasmic expression was higher in nondysplasia/mild ED and moderate/severe ED compared to NOM (<i>P</i> = .03, <i>P</i> < .0001, respectively). Significantly higher cytoplasmic XRCC-1 expression in OL (<i>P</i> < .0001) was observed. <h3>Conclusions</h3> 8-OHdG plays a role in the onset of multiple synchronous OL and the severity of ED. The subcellular level of Ref-1 implies different roles according to the ED degree. Cytoplasmic XRCC-1 expression indicates a DNA repair mechanism failure during oral carcinogenesis.

ASSOCIATION OF IMMUNOHISTOCHEMICAL EXPRESSION OF 8OHDG WITH THE PATHOGENESIS ACTINIC CHEILITIS

<h3>Objectives</h3> The aim of this study was to investigate the immunohistochemical expression of 8-OHdG in 57 cases of actinic cheilitis (AC) and its association with clinicopathologic parameters. <h3>Study Design</h3> The expression of 8-OHdG was evaluated semiquantitatively and the data were analyzed using the nonparametric Mann-Whitney and Kruskal-Wallis tests to identify statistically significant differences in the expression of 8-OHdG according to the World Health Organization histopathologic grading of oral epithelial dysplasia in the AC samples analyzed. <h3>Results</h3> Most cases exhibited strong immunoreactivity to the anti-8-OHdG antibody (64.9%). No significant differences were observed in the expression of 8-OHdG according to the clinical characteristics of AC or between the different degrees of epithelial dysplasia (<i>P</i> = .35). <h3>Conclusions</h3> The strong immunoexpression of 8-OHdG regardless of the morphologic severity of AC demonstrates the participation of oxidative DNA damage in the pathogenesis of this condition.

Mucinous Cystic Neoplasm of the Liver With Associated Neuroendocrine Carcinoma: A Case Report

Abstract Mucinous cystic neoplasms (MCNs) of the liver are relatively rare tumors that constitute less than 5% of liver cysts and are subcategorized into low/intermediate- and high-grade lesions based on the degree of epithelial dysplasia. An associated invasive carcinoma component occurs in 6% of cases, usually as adenocarcinoma with tubular growth. The liver is a frequent metastatic site for neuroendocrine carcinomas (NECs), whereas primary hepatic NECs are extremely rare. We present the case of a 63-year-old woman with a history of choledochal cyst, who now presented with abdominal pain. Computed tomography showed a multilocular cystic lesion in the liver. The cyst was surgically enucleated, and the histological examination revealed an MCN with low-grade dysplasia, with an associated invasive large cell NEC. To our knowledge, this is the first report in the literature of a biliary MCN with associated NEC.

Efficacy of Lasers in the Treatment of Tobacco Abuse Induced Oral Leukoplakia

Background: Oral leukoplakia is defined as a white patch or plaque, which cannot be characterized clinically or histopathologically as any other disease entity and is recognized as a common precancerous lesion of the oral mucous membrane. Definitive management crucial due to its notoriety for recurrences and malignant transformation depending on the anatomic location, clinical features, degree of epithelial dysplasia and causative factors. High power pulse diode laser has some advantages like less pain, swelling, prevention of metastasis, edema, less bleeding and infection. The prime objective of the study was to evaluate clinically and histopathologically the disease course with six monthly follow up. Methods: Thirty cases who had white lesion in the buccal mucosa with positive history of oral tobacco abuse, clinically diagnosed cases of oral leukoplakia confirmed by histopathology were selected for inclusion in the study and treated by LASER. The outcomes after the clinical and histopathologic determinants were processed with standard statistical tests, the results were derived and findings concluded. Results: Cases were distributed as per the size and histopathologic report and LASER ablation was administered Recurrence was noticed in 4 cases (16.6%) after six months follow up. No case transformed to malignancy during the study follow up period. Conclusion: Management of oral leukoplakia prevents not only recurrence and malignant transformation, but also postoperative dysfunction. Laser ablation of tobacco abuse induced leukoplakia is a simple effective and safe alternative to conventional surgical local excision with predictable outcome which can be undertaken as a routine OPD day care set up.

CLINICOPATHOLOGICAL CHARACTERIZATION OF 196 CASES OF EPITHELIAL DYSPLASIA AND ORAL SQUAMOUS CELL CARCINOMA

Potentially malignant disorders are characterized by different degrees of epithelial dysplasia (ED), an unpredictable course, and variable transformation potential for squamous cell carcinoma (SCC). Objective: To describe the clinicopathological profile of 196 cases of ED and SCC diagnosed from 2002-2018. Study design: Data regarding age, sex, clinical aspect, size, lesion location, type of biopsy, and clinical hypothesis (CH) were analyzed. Results: The mean age of the patients was 57 years for ED and SCC, with no predilection for sex. Most EDs (51.5%) presented as white plaques (P< .05) and SCCs as ulcers (62.7%; P< .05). SCCs exhibited the largest sizes, followed by carcinoma in situ and ED. The floor of mouth was the region most affected by SCCs (32.5%; P< .05). EDs were distributed equally between the regions and carcinoma in situ predominated on the palate (75%; P< .05). Incisional biopsy was performed in 50.5% of the cases. The equivalence between CH and histopathological diagnosis occurred in 83.3% of SCCs, and EDs had CH of leukoplakia (P< .05). Conclusion: The knowledge of the clinicopathological profile of ED and SCC allows for a better understanding of the factors commonly associated with malignant transformation. Potentially malignant disorders are characterized by different degrees of epithelial dysplasia (ED), an unpredictable course, and variable transformation potential for squamous cell carcinoma (SCC). Objective: To describe the clinicopathological profile of 196 cases of ED and SCC diagnosed from 2002-2018. Study design: Data regarding age, sex, clinical aspect, size, lesion location, type of biopsy, and clinical hypothesis (CH) were analyzed. Results: The mean age of the patients was 57 years for ED and SCC, with no predilection for sex. Most EDs (51.5%) presented as white plaques (P< .05) and SCCs as ulcers (62.7%; P< .05). SCCs exhibited the largest sizes, followed by carcinoma in situ and ED. The floor of mouth was the region most affected by SCCs (32.5%; P< .05). EDs were distributed equally between the regions and carcinoma in situ predominated on the palate (75%; P< .05). Incisional biopsy was performed in 50.5% of the cases. The equivalence between CH and histopathological diagnosis occurred in 83.3% of SCCs, and EDs had CH of leukoplakia (P< .05). Conclusion: The knowledge of the clinicopathological profile of ED and SCC allows for a better understanding of the factors commonly associated with malignant transformation.

EVALUATION OF INFLAMMATORY MARKERS IN POTENTIALLY MALIGNANT DISORDERS OF THE ORAL CAVITY

Objective: The aim this study was to evaluate the expression of inflammatory markers in potentially malignant disorders of oral cavity (leukoplakia) and its relationship with the degree of epithelial dysplasia. Study design: Immunohistochemistry was used to identify the number (cells/mm2) of interleukin 17 (IL-17+), neutrophil (CD66 b+), matrix metalloproteinase‐9 (MMP-9+) cells, and neoformed microvessels (CD105+) in the subepithelial region of leukoplakia samples from 31 patients. Evaluation of IL‐17 expression in keratinocytes cells was semiquantitative and performed by assigning scores. Samples of healthy oral mucosa (n = 10) were used as controls. Results: The classification of epithelial dysplasia by the binary grading system totaled 17 samples with high risk and 14 samples with low risk of malignant transformation. Irrespective of the severity of epithelial dysplasia, the counts of inflammatory markers (CD66 b, IL-17, MMP-9, and CD105) were higher in the leukoplakia group compared to controls (P< .05 for all comparisons). In addition, the intraepithelial expression of IL-17 was high in leukoplakia samples (44%) and absent/low in the control group (100%; P< .05). Conclusions: This study showed that potentially malignant disorders of oral cavity are characterized by a high count of inflammatory markers. Objective: The aim this study was to evaluate the expression of inflammatory markers in potentially malignant disorders of oral cavity (leukoplakia) and its relationship with the degree of epithelial dysplasia. Study design: Immunohistochemistry was used to identify the number (cells/mm2) of interleukin 17 (IL-17+), neutrophil (CD66 b+), matrix metalloproteinase‐9 (MMP-9+) cells, and neoformed microvessels (CD105+) in the subepithelial region of leukoplakia samples from 31 patients. Evaluation of IL‐17 expression in keratinocytes cells was semiquantitative and performed by assigning scores. Samples of healthy oral mucosa (n = 10) were used as controls. Results: The classification of epithelial dysplasia by the binary grading system totaled 17 samples with high risk and 14 samples with low risk of malignant transformation. Irrespective of the severity of epithelial dysplasia, the counts of inflammatory markers (CD66 b, IL-17, MMP-9, and CD105) were higher in the leukoplakia group compared to controls (P< .05 for all comparisons). In addition, the intraepithelial expression of IL-17 was high in leukoplakia samples (44%) and absent/low in the control group (100%; P< .05). Conclusions: This study showed that potentially malignant disorders of oral cavity are characterized by a high count of inflammatory markers.

CHARACTERIZATION OF ACTINIC CHEILITIS AS A POTENTIALLY MALIGNANT ORAL DISORDER

Actinic cheilitis (AC) is caused by chronic exposure to ultraviolet (UV) radiation, affecting mainly the lip of white people aged 50 or older, with loss of mucocutaneous delimitation. The question remains whether AC has the potential for malignancy. Currently, it is still not considered a potentially malignant oral disorder (PMOD) due to the lack of studies with a consistent sample. Objective: To characterize AC as a PMOD by studying the index of malignant transformation and clinicopathological correlation. Study design: A total of 182 clinical files of patients with AC were evaluated. Parametric and nonparametric statistical tests were used with a significance level of 5%. Results: AC affects mainly the lower lip of white men over 50 years of age who suffer from chronic exposure to the sun. We found that the probability of malignancy may be high mainly when it is associated with smoking. The percentual of malignant transformation was 28.02%. Microscopic analysis revealed that cellular atypia, inflammatory infiltrate, and solar elastosis are common features. In this study, a close relationship was found between the intensity of the inflammatory process and the degree of epithelial dysplasia in AC. Conclusion: AC is a potentially malignant disorder with high malignancy rate, even higher than some classic PMOD cases.

Histopathological features of photodamage and mast cell infiltrate in actinic cheilitis with different grades of epithelial dysplasia.

Actinic cheilitis is induced by chronic exposure to ultraviolet radiation and shows solar elastosis, a feature that has been associated with mast cell infiltrates. This study aimed to investigate the area of solar elastosis, collagen loss, and mast cell infiltrates in a series of actinic cheilitis. We evaluated the epithelial dysplasia in 52 cases of actinic cheilitis and the solar elastosis with Weigert's resorcin-fuchsin. Collagen loss was evaluated with Picrosirius red, analyzed under polarized microscopy, and scored from 1 to 3. Elastosis proportionate area (EPA) was calculated with image software. Mast cells were highlighted with toluidine blue stain. EPA varied from 2% to 45%, with a mean of 17.1% in the cases, with no differences among epithelial dysplasia degrees. Most cases presented collagen loss scores of 2 or 3, and higher loss of type I collagen was associated with older age. Mast cell density was higher in severe epithelial dysplasia (P = 0.002) and in high-risk cases (P = 0.01). Actinic cheilitis presented variable EPA and marked loss of type I collagen; however, these features were not associated with the degrees of epithelial dysplasia. Besides, mast cell density increased with epithelial dysplasia worsening and this was not associated with elastosis area or collagen loss.

HUMAN PAPILLOMA VIRUS–ASSOCIATED ORAL EPITHELIAL DYSPLASIA: A SERIES OF CASES WITH CLINICAL FEATURES

Human papilloma virus (HPV) could be found in oral potentially malignant disorders (OPMD) with multiple clinical presentations. However, there are dysplastic intraepithelial lesions associated with HPV harboring histopathologic findings that should be differentiated from classic epithelial dysplasias. The aim of this study is to present a series of cases of HPV-associated oral epithelial dysplasia, highlighting the role of local factors. Age, gender, location site, tobacco use, alcohol habit, chief complaint, clinical presentation, chronic mechanical irritation, degree of epithelial dysplasia, and polymerase chain reaction (PCR)-HPV genotype were recorded. Further research is needed to address clinical aspects of HPV epithelial dysplasia and its prognosis. Oral HPV infection is not similar to cervical infection due to the presence of other factors that could modify the behavior of the virus. Human papilloma virus (HPV) could be found in oral potentially malignant disorders (OPMD) with multiple clinical presentations. However, there are dysplastic intraepithelial lesions associated with HPV harboring histopathologic findings that should be differentiated from classic epithelial dysplasias. The aim of this study is to present a series of cases of HPV-associated oral epithelial dysplasia, highlighting the role of local factors. Age, gender, location site, tobacco use, alcohol habit, chief complaint, clinical presentation, chronic mechanical irritation, degree of epithelial dysplasia, and polymerase chain reaction (PCR)-HPV genotype were recorded. Further research is needed to address clinical aspects of HPV epithelial dysplasia and its prognosis. Oral HPV infection is not similar to cervical infection due to the presence of other factors that could modify the behavior of the virus.

TWIST AND E-CADHERIN IMMUNOEXPRESSION IN ACTINIC CHEILITES

Objective To investigate the immunohistochemical expression of TWIST and E-cadherin in actinic cheilitis (AC). Study Design The immunohistochemical expression of TWIST and E-cadherin was analyzed in 86 cases of AC with varying degrees of epithelial dysplasia. The epithelial immunostaining was semi-quantitatively evaluated according to the scores: (1) 75% positive cells. Median comparisons of E-cadherin and TWIST expression scores according to histologic grade were performed using the nonparametric Mann-Whitney test. Results Analysis of TWIST and E-cadherin expression in the AC epithelium revealed membrane and cytoplasmic immunoreactivity for E-cadherin in all epithelial layers except in the keratin layer. For TWIST, nuclear and cytoplasmic immunoreactivity were observed in all epithelial layers except in the keratin layer. No statistically significant differences were observed in the medians of the E-cadherin and TWIST scores in relation to the histologic grade of the AC (P > .05). Conclusions The results of this study suggest that the high immunoexpression of TWIST and E-cadherin has been observed in cases of AC; however, these proteins do not appear to be associated with the varying degrees of epithelial dysplasia in the analyzed cases.

USE OF THERMOGRAPHY FOR DIAGNOSIS OF ACTINIC CHEILITS AND LOWER LIP SQUAMOUS CELL CARCINOMA

Lower lip squamous cell carcinoma (LLSCC) represents frequent lip malignant neoplasms, and the majority is preceded by actinic cheilitis (AC), a potentially malignant disorder. In this context, we report 3 cases of AC and 1 of LLSCC, emphasizing the importance of thermography as an auxiliary tool in diagnosis. In AC and LLSCC, thermography showed, respectively, whitish areas with higher heat emission and reddish circular area of irregular thermal distribution. After acquisition of thermography images, incisional biopsies were performed to evaluate microscopic alterations according to the criteria described by the World Health Organization (2017). Of the AC cases, 1 was diagnosed as mild epithelial dysplasia and 2 were moderate epithelial dysplasia. LLSCC was confirmed on anatomopathologic examination. As a result, we observed that thermography is not able to distinguish the different degrees of epithelial dysplasia found in AC, but it is a new imaging method useful in distinguishing AC from LLSCC.

Actinic cheilitis: Morphometric parameters and its relationship with the degree of epithelial dysplasia

Actinic cheilitis (AC) is a potentially malignant lesion caused by chronic sun exposure. This study aimed to evaluate the relationship between the degree of epithelial dysplasia and morphometric findings in AC. Sixty-eight slides of AC cases were selected and classified according to the grade of epithelial dysplasia, following morphologic criteria of World Health Organization. For morphometric analysis, the slides were scanned and images were analyzed using Pannoramic Viewer software. We obtained vertical measurements of the parameters: thicknesses of the keratin layer, lamina propria and zone of solar elastosis in three selected fields. Thirty-seven (54.4%) of the analyzed cases were classified as none/mild dysplasia and 31 (45.6%) as moderate/severe epithelial dysplasia. Cases with a moderate/severe dysplasia exhibited a thicker layer of keratin (median = 0.055 mm) than none/mild dysplasia (median = 0.045 mm) (p = 0.033). No significant differences in the thicknesses of lamina propria and zone of solar elastosis were observed according to the grade of epithelial dysplasia. A positive significant correlation between keratin layer and lamina propria thicknesses was found (p = 0.019). Based on our findings, rigorous clinical follow-up should be recommended for patients whose histopathological examination shows a greater thickness of the keratin layer.

Regulation of proliferation and cell cycle by protein regulator of cytokinesis 1 in oral squamous cell carcinoma

Protein regulator of cytokinesis 1 (PRC1), a microtubule-associated protein, has emerged as a critical regulator of proliferation and apoptosis, acting predominantly in numerous tumors. However, its function in oral squamous cell carcinoma (OSCC) is still unknown. To establish the roles of PRC1 in OSCC, 95 oral clinical samples (54 OSCC, 24 oral leukoplakia [OLK], and 17 normal oral mucosa) and seven oral cell lines (6 OSCC and 1 normal oral cell lines) were analyzed using a series of molecular and genomic assays both in vivo and in vitro were conducted in this study. Herein, we provide evidence demonstrating that expression of PRC1 closely correlates with the degree of epithelial dysplasia in OLK (n = 24) (p < 0.001), and the poor differentiation, large tumor volume, lymph node metastasis, and high-clinical stage in OSCC (n = 54) (p < 0.05), illustrating that PRC1 has a promotive influence on tumor progression in OSCC. Simultaneously, we observed that PRC1 knockdown in OSCC cell lines caused G2/M phase arrest (p < 0.05), inhibited cell proliferation in vitro (p < 0.05) and tumor growth in vivo (p < 0.001). Furthermore, the effects of PRC1 on the regulation of proliferation and cell cycle transition in OSCC samples were mediated by p53. The p53/PRC1/EGFR signaling pathway was found to be implicated in the tumor progression of OSCC. Based on our data, we demonstrate that PRC1 is a key factor in regulating proliferation and the cell cycle, pointing to the potential benefits of PRC1-targeted therapies for OSCC.

Role of hypoxia in malignant transformation of oral submucous fibrosis

Context: In the Indian subcontinent and Southeast Asia, habit of chewing areca nut has been recognized as one of the most important risk factors leading to a ubiquitous oral potentially malignant disorder (OPMD), oral submucous fibrosis (OSMF).In OSMF, owing to fibrosis in the connective tissue, there is narrowing of blood vessels which further results in compromised blood supply to the local tissue milieu. This tissue hypoxia elicits the activation of the transcription factor Hypoxia-inducible factor 1-alpha (HIF-1 α). In OSMF, its expression shows significant correlation with degree of epithelial dysplasia. Aim: This study aims to evaluate the expression of HIF-1 α in OSMF. Settings and Design: Seventy-five histopathologically proven cases of OSMF were included in the study. The tissue sections were studied for histopathological evaluation and HIF-1α expression. Statistical Analysis Used: Descriptive and inferential statistics using one-way ANOVA and multiple comparison using Kruskal–Wallis test were used. Results: Comparison of HIF-1α expression in different grades of OSMF was done. There were 47 cases without dysplasia, whereas 16 and 12 were of low-risk and high-risk dysplasia, respectively. On comparison of HIF-1α expression in different grades of OSMF, it was found to increase significantly from normal oral mucosa (1.43 ± 0.89) to no dysplasia (3.97 ± 2.75) to low-risk epithelial dysplasia (4.93 ± 1.76) to high-risk epithelial dysplasia (5.66 ± 2.01). Conclusion: The altered expression of HIF-1α can signify the disturbed epithelial-mesenchymal interaction which indicates progression toward the malignant transformation of OSMF. Thus, HIF-1 α expression showed good correlation with increase in grades of epithelial dysplasia and thus can assist for grading/quantifying oral epithelial dysplasia in OSMF.

PP - HISTOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL ANALYSIS OF WNT/β-CATENIN SIGNALING PATHWAY PROTEINS IN ACTINIC CHEILITIS

Actinic cheilitis (AC) is a potentially malignant disorder of the lips that is caused by chronic exposure to ultraviolet radiation. The Wnt/β-catenin signaling pathway - also named the canonical signaling pathway - acts in cell proliferation and is involved with tumor development and progression. Some of these molecules have already been identified in AC. Thus, the aim of this study was to comparatively evaluate the histopathological features and the presence of Wnt/β-catenin signaling pathway proteins in AC. For this purpose, immunohistochemical reactions against Wnt1, Wnt5a, β-catenin, axin, APC and cyclin D1 were performed and evaluated in accordance with histopathological epithelial dysplasia grading, using the World Health Organization classification and the binary classification system. The results showed positivity for Wnt 1 (96.7%), cyclin D1 (75.4%), APC (96.7%), axin (95%) and cytoplasmic β-catenin staining (81.9%) and negativity for Wnt 5a (100%). Furthermore, Wnt1, cyclin D1, APC and axin showed an increased labeling index related with the degree of epithelial dysplasia using the binary system. In conclusion, it was possible to state that Wnt 1, cyclin D1 and β-catenin seems to act as tumor promoters by activating the canonical signaling pathway, whereas APC and axin seems to act as tumor promoters by activating the non-canonical signaling pathways.