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OBJECTIVES: To update the current evidence on the malignant transformation of oral leukoplakia (OL), including all studies published worldwide on the subject, selected with the maximum rigor regarding eligibility. MATERIALS AND METHODS: MEDLINE, Embase, Web of Science and Scopus were searched for studies published before June-2024, with no lower date limit. The risk of bias was analyzed using the Joanna Briggs Institute tool for meta-analyses of proportions. We carried out meta-analyses, explored heterogeneity across subgroups and identified risk factors with potential prognostic value. RESULTS: Fifty-five studies (41,231 with OL) were included. The pooled malignant transformation proportion for OL was 6.64% (95% CI = 5.21-8.21). The malignant transformation did not significantly vary by time periods (p = 0.75), 5.35% prior to 1978, 7.06% from 1979 to 2007 and 6.97% during more recent times. The risk factors that significantly had a higher impact on malignant transformation were the non-homogeneous leukoplakias (RR = 4.23, 95% CI = 3.31-5.39, p < 0.001), the larger size (RR = 2.08, 1.45-2.96, p < 0.001), leukoplakia located on the lateral border of tongue (malignant transformation = 12.71%; RR = 2.09, 95% CI = 1.48-2.95, p < 0.001), smoking (RR = 1.64, 95% CI = 1.25-2.15, p < 0.001), and the presence of epithelial dysplasia (RR = 2.75, 95% CI = 2.26-3.35, p < 0.001). CONCLUSIONS: OL presents a considerable malignant transformation probability that is especially increased in large non-homogeneous lesions in smokers, located on the lateral border of the tongue, with epithelial dysplasia.
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OBJECTIVE: This systematic review and meta-analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites. MATERIALS AND METHODS: A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered. RESULTS: Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59-1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09-1.09]) for recurrence was observed when cold-knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN. CONCLUSION: There is no difference in recurrence risk post-surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches.
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OBJECTIVES: Chemoprevention can be a treatment for potentially malignant lesions (PMLs). We aimed to evaluate whether artemisinin (ART) and cisplatin (CSP) are associated with apoptosis and immunogenic cell death (ICD) in vitro, using oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cell lines, and whether these compounds prevent OL progression in vivo. METHODS: Normal keratinocytes (HaCat), Dysplastic oral cells (DOK), and oral squamous cell carcinoma (SCC-180) cell lines were treated with ART, CSP, and ART + CSP to analyze cytotoxicity, genotoxicity, cell migration, and increased expression of proteins related to apoptosis and ICD. Additionally, 41 mice were induced with OL using 4NQO, treated with ART and CSP, and their tongues were histologically analyzed. RESULTS: In vitro, CSP and CSP + ART showed dose-dependent cytotoxicity and reduced SCC-180 migration. No treatment was genotoxic, and none induced expression of proteins related to apoptosis and ICD; CSP considerably reduced High-mobility group box-1 (HMGB-1) protein expression in SCC-180. In vivo, there was a delay in OL progression with ART and CSP treatment; however, by the 16th week, only CSP prevented progression to OSCC. CONCLUSION: Expression of proteins related to ICD and apoptosis did not increase with treatments, and CSP was shown to reduce immunogenic pathways in SCC-180, while reducing cell migration. ART did not prevent the malignant progression of OL in vivo; CSP did despite significant adverse effects.
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Apoptose , Artemisininas , Movimento Celular , Cisplatino , Progressão da Doença , Leucoplasia Oral , Neoplasias Bucais , Artemisininas/farmacologia , Animais , Leucoplasia Oral/patologia , Leucoplasia Oral/tratamento farmacológico , Humanos , Cisplatino/farmacologia , Camundongos , Neoplasias Bucais/patologia , Neoplasias Bucais/tratamento farmacológico , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proteína HMGB1/metabolismo , Antineoplásicos/farmacologiaRESUMO
OBJECTIVE: This study aims to analyze the prevalence of Candida spp. colonization in oral leukoplakia and oral lichen planus lesions, verify the influence of systemic and local factors, besides identify and determine the in vitro antifungal susceptibility profile of Candida species. MATERIALS AND METHODS: Samples were collected by swabbing from oral lesions and healthy mucosa and cultured on Sabouraud Dextrose and CHROMagar® Candida plates. Species identification was confirmed with MALDI-TOF MS analysis. RESULTS: Candida spp. was found in 36.8% of cases of oral leukoplakia and 18.2% of cases of oral lichen planus. Candida albicans was the only species found in oral lichen planus lesions (n = 2, 100%) and the most prevalent in oral leukoplakia (n = 5, 76.4%). Among the non-albicans Candida species found in oral leukoplakia were C. parapsilosis (n = 2, 25.5%) and C. tropicalis (n = 1, 14.1%). Candida isolates were susceptible to all antifungals tested. CONCLUSION: C. albicans was the most commonly found species in the studied lesions. No correlation was found between systemic and local factors with positive cases of oral lichen planus. However, smoking and alcohol consumption may be associated with positive cases of oral leukoplakia, especially the non-homogeneous clinical form. In addition, there is a possible predisposition to associated Candida colonization in cases of epithelial dysplasia found in oral leukoplakia. The antifungal medications tested showed excellent efficacy against isolates.
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Antifúngicos , Candida , Leucoplasia Oral , Líquen Plano Bucal , Testes de Sensibilidade Microbiana , Humanos , Líquen Plano Bucal/microbiologia , Líquen Plano Bucal/patologia , Leucoplasia Oral/microbiologia , Leucoplasia Oral/patologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida/classificação , Masculino , Pessoa de Meia-Idade , Feminino , Antifúngicos/farmacologia , Adulto , Idoso , Candidíase Bucal/microbiologia , Adulto Jovem , PrevalênciaRESUMO
Oral leukoplakia is the most frequent and potentially malignant lesion of the oral cavity. Although dysplasia grading remains the main factor for risk assessment, challenges persist in determining the exact risk of transformation, and the literature has focused on studying alternative biomarkers. The interaction between dysplastic epithelial cells and the microenvironment starts early, and the communication is mainly mediated by lymphocytes, inflammatory factors, fibroblasts, and the extracellular matrix, leading to dysplastic progression. Leukoplakia-infiltrating leukocytes (LILs) and leukoplakia-associated fibroblasts (LAFs) play crucial roles in the dysplastic microenvironment. The immune response is related to intraepithelial T lymphocyte infiltration, mechanisms of immunosuppression coordinated by regulatory T cells, M2 macrophage polarization, and increased numbers of Langerhans cells; in contrast, fibroblastic and extracellular matrix factors are associated with increased numbers of pro-tumorigenic myofibroblasts, increased expression of metalloproteinases vs. decreased expression of TIMPs, and increased expression of chemokines and other inflammatory mediators. The microenvironment offers insights into the progression of leukoplakia to carcinoma, and understanding the complexity of the oral microenvironment in potentially malignant diseases aids in determining the risk of malignant transformation and proposing new therapeutic alternatives.
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BACKGROUND: To investigate the association between tooth loss and oral potentially malignant disorders and oral squamous cell carcinoma, focusing on epidemiological factors and genetic variants. METHODS: Case-control study, including histologically confirmed oral potentially malignant disorders and oral squamous cell carcinoma cases and healthy controls. Unadjusted and adjusted odds ratios for this association were calculated. Single-nucleotides polymorphisms were tested for individuals with and without missing teeth. RESULTS: Case individuals were more edentulous while controls had fewer missing teeth (p = 0.006). There was an increased risk for the outcomes associated with edentulism (OR = 6.95, p = 0.000), even after adjustments for educational level (OR = 4.7, p = 0.034) and smoking habits (OR = 5.01, p = 0.022). Among individuals with tooth loss, rs1533767 (WNT11), rs3923087, and rs11867417 (AXIN2) were associated with the outcomes (OR = 1.67, p = 0.03, OR = 0.53, p = 0.05, and OR = 0.42, p = 0.00, respectively). CONCLUSIONS: Tooth loss could increase the risk for oral potentially malignant disorders and oral squamous cell carcinoma.
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Carcinoma de Células Escamosas , Neoplasias Bucais , Perda de Dente , Humanos , Neoplasias Bucais/genética , Masculino , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/epidemiologia , Feminino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Perda de Dente/epidemiologia , Idoso , Polimorfismo de Nucleotídeo Único , Adulto , Predisposição Genética para Doença , Fatores de Risco , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Interação Gene-AmbienteRESUMO
Novos fármacos, como a artemisinina (ART), podem ser promissores no tratamento de lesões potencialmente malignas (LPM) e podem ser úteis quando usados em associação com outros quimioterápicos, especialmente na redução dos seus efeitos colaterais. A leucoplasia oral (LO) é a LPM mais comum da cavidade bucal e, pode evoluir para um carcinoma de células escamosas oral (CCEO). Não há terapia para evitar a sua transformação maligna, a quimioprevenção pode iniciar a morte celular imunogênica (MCI) que ativa o sistema imunológico para que reconheça e elimine as células malignas ou pré-malignas, sendo um potencial tratamento para as LPM. O presente estudo objetivou avaliar se a ART e a cisplatina (CSP) associadas ou não seriam capazes de induzir a MCI em linhagens celulares de LO (DOK) e CCEO SCC180). Material e métodos: As linhagens celulares HaCat (controle), DOK e SCC-180 foram tratadas por ART e CSP de forma combinada ou isolada, a fim de analisar a citotoxicidade e a genotoxicidade destes fármacos, além da capacidade destes em reduzir a migração celular e, se os compostos seriam capazes de induzir a expressão da proteína box de alta mobilidade (HGMB-1), caspase 3, 8, 9, e Calreticulina (CALR). Resultados: Em todas as linhagens celulares a CSP e CSP+ART causaram uma resposta dose dependente, apresentando maior citotoxicidade com doses mais altas, o que não foi observado com a ART. A formação de micronúcleos não foi observada no teste de genotoxicidade. A taxa de migração foi reduzida com as concentrações de IC50 de CSP e ART+CSP para as células de CCEO. Não foram encontradas expressões significativas de proteínas relacionadas à MCI ou apoptose nas linhagens de LO e CCEO, tratadas com ART, CSP ou ART+CSP, indicando que outro tipo de morte celular possa ter ocorrido. Conclusão: A MCI e a apoptose não foram evidenciadas como forma de morte celular após as linhagens de LO e CCEO receberem tratamentos com ART, CSP e a associação de ambas. Efeitos genotóxicos não foram observados nas doses testadas. O tratamento de CSP e ART+CSP foi capaz de reduzir a migração de células de CCEO. Também concluímos que novos estudos são necessários para elucidar se a ART e CSP podem ocasionar a MCI ou apoptose em linhagens celulares de LO e CCEO (AU)
New drugs, such as artemisinin (ART), may be promising in the treatment of potentially malignant lesions (PML) and may be useful when used in combination with other chemotherapy drugs, especially in reducing their side effects. Oral leukoplakia (OL) is the most common LPM of the oral cavity and can progress to oral squamous cell carcinoma (OSCC). There is no therapy to prevent its malignant transformation, chemoprevention can initiate immunogenic cell death (ICM) that activates the immune system to recognize and eliminate malignant or pre-malignant cells, being a potential treatment for LPM. The present study aimed to evaluate whether or not ART and cisplatin (CSP) combined would be capable of inducing MCI in LO (DOK) and CCEO SCC-180) cell lines. Material and methods: HaCat (control), DOK and SCC-180 cell lines were treated by ART and CSP in combination or alone, in order to analyze the cytotoxicity and genotoxicity of these drugs, in addition to their ability to reduce cell and, whether the compounds would be able to induce the expression of high mobility box protein (HGMB-1), caspase 3, 8, 9, and Calreticulin (CALR). Results: In cytotoxicity at higher doses, which was not observed with ART. The formation of micronuclei was not observed in the genotoxicity test. The migration rate was reduced with the IC50 concentrations of CSP and ART+CSP for OSCC cells. No significant expressions of proteins related to MCI or apoptosis were found in the LO and CCEO lines, treated with ART, CSP or ART+CSP, indicating that another type of cell death may have occurred. Conclusion: MCI and apoptosis were not evidenced as a form of cell death after the LO and CCEO lines received treatments with ART, CSP and the combination of both. Genotoxic effects were not observed at the doses tested. CSP and ART+CSP treatment was able to reduce OSCC cell migration. We also conclude that new studies are necessary to elucidate whether ART and CSP can cause MCI or apoptosis in LO and CCEO cell lines.(AU)
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Leucoplasia Oral , Imunomodulação , Carcinoma de Células Escamosas de Cabeça e Pescoço , Morte Celular Imunogênica , Células Apresentadoras de AntígenosRESUMO
PURPOSE: High-power diode laser emerges as a promising approach to the treatment of oral leukoplakia (OL); however, its short- and long-term effects have been barely explored. This study evaluated the postoperative endpoints and the recurrence rate of high-power diode laser treatment in a well-defined series of patients with OL. METHODS: A prospective analysis was performed on 22 individuals comprising 31 OL. The lesions were irradiated using the following protocol: Indium-Gallium-Arsenide diode laser, 808 nm, continuous-wave mode, 1.5-2.0 W, 780.0 ± 225.1 J, and 477.1 ± 131.8 s. Postoperative pain was assessed with a visual analog scale at three endpoints. Clinical follow-up was performed on all patients and the Kaplan-Meier test was used to analyze the probability of recurrence. RESULTS: The series consisted mostly of women (72.7%) with a mean age of 62.8 years. A single laser session was performed in 77.4% of cases. The median score on the scale that assessed pain on the 1st, 14th and 42nd postoperative day was 4, 1, and 0, respectively. The mean follow-up period per lesion was 28.6 months (range: 2-53 months). A complete response was observed in 93.5% of OL cases, while 6.5% had recurrence. The probability of recurrence at 39 months was 6.7%. No patient experienced malignant transformation. CONCLUSION: High-power diode laser for the treatment of OL is safe and effective during the trans- and postoperative period. These findings represent an alternative approach to the management of OL, mainly because a low recurrence rate was observed.
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Lasers Semicondutores , Leucoplasia Oral , Humanos , Feminino , Pessoa de Meia-Idade , Lasers Semicondutores/uso terapêutico , Leucoplasia Oral/radioterapia , Leucoplasia Oral/cirurgia , Leucoplasia Oral/patologia , Dor Pós-Operatória , Transformação Celular Neoplásica , Medição da DorRESUMO
The gold standard for the diagnosis of oral cancer is the microscopic analysis of specimens removed preferentially through incisional biopsies of oral mucosa with a clinically detected suspicious lesion. This dataset contains captured histopathological images of oral squamous cell carcinoma and leukoplakia. A total of 237 images were captured, 89 leukoplakia with dysplasia images, 57 leukoplakia without dysplasia images and 91 carcinoma images. The images were captured with an optical light microscope, using 10x and 40x objectives, attached to a microscope camera and visualized through a software. The images were saved in PNG format at 2048 × 1536 size pixels and they refer to hematoxylin-eosin stained histopathologic slides from biopsies performed between 2010 and 2021 in patients managed at the Oral Diagnosis project (NDB) of the Federal University of Espírito Santo (UFES). Oral leukoplakias were represented by samples with and without epithelial dysplasia. Since the diagnosis considers socio-demographic data (gender, age and skin color) as well as clinical data (tobacco use, alcohol consumption, sun exposure, fundamental lesion, type of biopsy, lesion color, lesion surface and lesion diagnosis), this information was also collected. So, our aim by releasing this dataset NDB-UFES is to provide a new dataset to be used by researchers in Artificial Intelligence (machine and deep learning) to develop tools to assist clinicians and pathologists in the automated diagnosis of oral potentially malignant disorders and oral squamous cell carcinoma.
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The search for biomarkers associated with oral leukoplakia malignant transformation is critical for early diagnosis and improved prognosis of oral cancer patients. This systematic review and meta-analysis aimed to assess protein-based markers potentially associated with malignant transformation of oral leukoplakia. Five database and the grey literature were searched. In total, 142 studies were included for qualitative synthesis, where 173 proteins were investigated due to their potential role in malignant progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC). The abundance of these proteins was analyzed in fixed tissues and/or biofluid samples, mainly by immunohistochemistry and ELISA, and 12 were shared by both samples. Enrichment analysis revealed that the differential abundant proteins are mostly involved with regulation of cell death, regulation of cell proliferation, and regulation of apoptotic process. Also, these proteins are mainly expressed in the extracellular region (55.5%), cell surface (24.8%), and vesicles (49.1%). The meta-analysis revealed that the proteins related to tumor progression, PD-L1, Mdm2, and Mucin-4 were significantly associated with greater abundance in OSCC patients, with an Odds Ratio (OR) of 0.12 (95% CI: 0.04-0.40), 0.44 (95% CI: 0.24-0.81), and 0.18 (95% CI: 0.04-0.86), respectively, with a moderate certainty of evidence. The results indicate a set of proteins that have been investigated across OSCC initiation and progression, and whose transcriptional expression is associated with clinical characteristics relevant to the prognosis and aggressiveness. Further verification and validation of this biomarkers set are strongly recommended for future clinical application.
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BACKGROUND: Fibroblast growth factor receptor 1 is a potential prognostic factor for tongue squamous cell carcinoma and is associated with oral epithelial dysplasia grade in oral leukoplakia. METHODS: Thirty cases of tongue squamous cell carcinoma and 30 cases of oral leukoplakia were analyzed. Fibroblast growth factor receptor 1 and phosphorylated Akt protein expression were analyzed by immunohistochemistry and quantified using a digital algorithm. Fibroblast growth factor receptor 1 gene amplification was analyzed by fluorescent in situ hybridization in the tongue squamous cell carcinoma cases. RESULTS: Clinical appearance and dysplasia grade were correlated with oral leukoplakia malignant transformation. Oral leukoplakia cases presenting high fibroblast growth factor receptor 1 expression showed a higher risk of malignant transformation (p = 0.016, HR: 7.3, 95% CI: 1.4-37.4). Phosphorylated Akt showed faint to no expression in oral leukoplakia, which did not correlate with dysplasia grade or malignant transformation. High expression of fibroblast growth factor receptor 1 and phosohorylated Akt were associated with poor overall survival and disease-free survival in tongue squamous cell carcinoma, although only fibroblast growth factor receptor 1 expression was significantly associated with poor overall survival (p = 0.024; HR: 4.9, 95% CI: 1.2-19.9). Cases presenting double fibroblast growth factor receptor 1/phosphorylated Akt overexpression (n = 8) showed markedly impaired overall survival (p = 0.020; HR: 6.4, 95% CI: 1.3-31.1) and disease-free survival (p = 0.001, HR: 13.0, 95% CI: 3.0-55.7). Fibroblast growth factor receptor 1 amplification was observed in 16.6% of tongue squamous cell carcinoma cases, being correlated with vascular and neural invasion (p = 0.001 and 0.017, respectively), but not with fibroblast growth factor receptor 1 protein expression, overall survival, or disease-free survival. CONCLUSION: Fibroblast growth factor receptor 1 protein expression is an important prognostic factor in oral leukoplakia and tongue squamous cell carcinoma.
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Carcinoma de Células Escamosas , Neoplasias da Língua , Humanos , Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/patologia , Prognóstico , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Hibridização in Situ Fluorescente , Proteínas Proto-Oncogênicas c-akt/genética , Leucoplasia Oral/patologia , Língua/patologiaRESUMO
Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) are oral potentially malignant disorders (OPMDs) that microscopically show no or varying degrees of dysplasia. Even sharing clinical and microscopic aspects, PVL shows a more aggressive clinical behaviour, with a malignant transformation rate greater than 40%. Inflammatory infiltrate associated with dysplastic lesions may favour malignant transformation of OPMDs. This study aimed to evaluate the density of T cells and cytokines in dysplastic lesions from OL and PVL patients. Additionally, we evaluated whether soluble products produced in vitro by dysplastic keratinocytes are capable of modulating apoptosis rates and Th phenotype (Th1, Th2, Th17 and Treg) of peripheral blood mononuclear cells. The density of CD3, CD4 and CD8 T cells was assessed by immunohistochemistry. Cytokines and chemokines profile from frozen tissue samples were analysed using the LUMINEX system. Apoptosis rates and Th phenotype modulation were evaluated by flow cytometry. Our results showed an increase in the number of CD8 T cell in the subepithelial region from PVL dysplastic lesions in relation to OL samples. PVL showed increased levels of IL-5 and a decrease in IL-1ß and IFN-γ levels compared to OL. Soluble products of PVL and oral carcinoma cell cultures were able to reduce apoptosis rate and promote an imbalance of Th1/Th2 and Th17/Treg. The high-subepithelial density of CD8 T cells and immune imbalance of T lymphocytes subsets probably play an important role in the pathogenesis of PVL and may explain its more aggressive behaviour in relation to OL.
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Neoplasias Bucais , Lesões Pré-Cancerosas , Humanos , Leucócitos Mononucleares/patologia , Leucoplasia Oral/patologia , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Linfócitos T CD8-Positivos/patologia , Citocinas , Transformação Celular NeoplásicaRESUMO
Abstract Type VII collagen (Col7) is a major component of anchoring fibrils. Col7 plays a role in tumor development and aggressiveness of cutaneous squamous cell carcinoma of recessive dystrophic epidermolysis bullosa. However, the role of Col7 in oral squamous cell carcinoma (OSCC) and oral leukoplakia (OL) remains largely unknown. Objective To elucidate the role of Col7 and its diagnostic potential during oral carcinogenesis. Methodology Col7 expression was immunohistochemically studied in 254 samples, including normal oral mucosa (NM), OL without dysplasia, OL with dysplasia, and OSCC. The correlation between Col7 expression and clinicopathologic parameters of OSCC was also determined. Results Col7 was present as a linear deposit at the basement membrane of NM, OL without dysplasia and OL with dysplasia, and at the tumor-stromal junction around tumor islands in OSCC. Discontinuity of expression was frequently observed in OL with dysplasia and OSCC. OSCC had the significantly lowest Col7 expression (p<0.0001). Compared with OL without dysplasia, OL with dysplasia showed significantly reduced Col7 expression. Patients in clinical stage 4 with positive nodes had low Col7 expression compared with those in clinical stage 1 and negative nodes, respectively. Conclusion Loss of Col7 is associated with tumorigenesis and aggressiveness in OSCC. A significantly reduced Col7 expression in OSCC implies that Col7 may be a useful marker for diagnosis and therapeutic targets.
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This report presents the clinical, microscopic and immunohistochemical aspects of a case of proliferative verrucous leukoplakia (PVL) mimicking oral lichen planus (OLP) in a 66-year-old woman. We also review the literature reporting cases of PVL mimicking OLP, where we found a higher prevalence in women who do not consume tobacco or alcohol. The initial manifestation of lichenoid areas was around the age of 59, with the diagnosis of PVL being established on average 6 years later, while malignant transformation occurred in 8 of the 22 cases at an average of 3.7 years after the final diagnosis of PVL. We emphasize the need for a close follow-up of any patient presenting white lesions of the oral mucosa. Lesions that are clinically and microscopically compatible with lichenoid reactions or OLP must be investigated and differentiated from PVL, which has a worse prognosis.
Este relato apresenta os aspectos clínicos, microscópicos e imuno-histoquímicos de um caso de leucoplasia verrucosa proliferativa (LPV) mimetizando líquen plano oral (LPO) em uma paciente do sexo feminino de 66 anos. Também revisamos a literatura relatando casos de LPV mimetizando LPO, onde encontramos maior prevalência em mulheres que não consomem tabaco ou álcool, com manifestação inicial de áreas liquenoides por volta dos 59 anos, sendo estabelecido o diagnóstico de LPV em média 6 anos depois, enquanto a transformação maligna ocorreu em 8 dos 22 casos em média 3,7 anos após o diagnóstico final de LPV. Ressaltamos a necessidade de acompanhamento rigoroso de qualquer paciente que apresente lesões brancas da mucosa oral, devendo ser investigadas lesões clinicamente e microscopicamente compatíveis com reações liquenóides ou LPO e diferenciadas da LPV, que tem pior prognóstico
Este reporte presenta los aspectos clínicos, microscópicos e inmunohistoquímicos de un caso de leucoplasia verrugosa proliferativa (LVP) simulando liquen plano oral (LPO) en una paciente de 66 años. También revisamos la literatura reportando casos de LVP simulando LPO, donde encontramos una mayor prevalencia en mujeres que no consumen tabaco ni alcohol, con una manifestación inicial de áreas liquenoides alrededor de los 59 años, estableciéndose el diagnóstico de LVP en promedio 6 años después, mientras que la transformación maligna ocurrió en 8 de los 22 casos en un promedio de 3,7 años después del diagnóstico final de LVP. Resaltamos la necesidad de un seguimiento estrecho de todo paciente que presente lesiones blanquecinas de la mucosa oral, que las lesiones clínica y microscópicamente compatibles con reacciones liquenoides o LPO deben ser investigadas y diferenciadas de la LVP, que tienen peor pronóstico.
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Las lesiones de la cavidad oral corresponden a un hallazgo frecuente y muchas veces difíciles de diagnosticar. Su correcto reconocimiento podría ser clave en detectar patologías que podrían cambiar el pronóstico del paciente. El objetivo de esta revisión es describir una clasificación de las lesiones de la cavidad oral que permita ayudar al diagnóstico en la práctica clínica. Para esto, se detallan y se describen las lesiones, orientando al diagnóstico y a la necesidad de biopsiar. Para simplificar la orientación diagnóstica, las lesiones se clasifican en 2 grandes grupos: tumorales y no tumorales. Las lesiones no tumorales se subdividen en lesiones de la mucosa oral y lesiones de la lengua.
Lesions of the oral cavity are frequent and often difficult to diagnose. However, correct recognition could change the patient's prognosis. This review aims to describe a classification of oral mucosa lesions, to help the diagnosis in clinical practice. The lesions are described for this, guiding the diagnosis and the need for biopsy. To simplify the diagnostic orientation, the lesions are classified into two groups: tumor and non-tumor lesions. Non-tumor lesions are subdivided into lesions of the oral mucosa and lesions of the tongue.
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Humanos , Mucosa Bucal/patologia , Biópsia/métodos , Boca/patologiaRESUMO
Objetivo: La leucoplasia oral es el desorden maligno de la mucosa bucal más prevalente a nivel global y su manejo clínico sigue siendo un desafío. Se llevó a cabo una revisión sistemática para determinar la eficacia clínica de la terapia fotodinámica mediada por ácido 5-aminolevulínico tópico como una alternativa de quimio-prevención para las diferen- tes formas clínicas de la leucoplasia oral. Materiales y métodos: Empleando términos MeSH, se realizó una búsqueda exhaustiva en diferentes bases digi- tales de ensayos clínicos publicados en inglés en los últimos 30 años acerca del uso de la terapia fotodinámica mediada por ácido 5-aminolevulínico tópico como fotosensibilizador, y radiación láser de baja intensidad o luz LED como posibles fuentes de iluminación. Resultados: La revisión sistematizada que aplicó la guía PRISMA mostró una eficacia del 88,6% para este modo de fototerapia en el manejo de leucoplasias orales, con un 60,7% de respuesta completa y 27,9% de respuesta parcial. Además, el tamaño de efecto fue mayor para las formas clíni- cas homogéneas con cambios displásicos, independientemen- te del tipo de fuente de luz. La ausencia de respuesta fue del 11,4%, pero la evidencia empleada en este análisis fue mo- derada. Conclusión: La terapia fotodinámica mediada por áci- do 5-aminolevulínico tópico parece ser una alternativa útil en el manejo onco-preventivo de lesiones de leucoplasia oral. Sin embargo, es recomendable ejecutar ensayos clínicos controla- dos y aleatorizados con metodologías homogéneas que per- mitan generar un meta-análisis con un alto nivel de evidencia
Aim: Oral leukoplakia is globally the most prevalent ma- lignant disorder of the oral mucosa and its clinical manage- ment remains a challenge. A systematic review was carried out to determine the clinical efficacy of photodynamic therapy mediated by topical 5-aminolevulinic acid as an alternative for chemoprevention in the different clinical forms of oral leu- koplakia. Materials and methods: Using MeSH terms, an ex- haustive search was carried out in different digital databases of clinical trials published in English in the last 30 years on the use of photodynamic therapy mediated by topical 5-ami- nolevulinic acid as a photosensitizer, and low-intensity laser radiation or LED light as possible lighting sources. Results: The systematized review using PRISMA guide- lines showed an efficacy of 88.6% for this mode of photother- apy in the management of oral leukoplakias, based on 60.7% of complete response and 27.9% of partial response. In addi- tion, the effect size was larger in homogeneous clinical forms with dysplastic changes, regardless of the type of light source. There was an 11.4% of absence of response, but the evidence used in this analysis was moderate. Conclusion: Photodynamic therapy mediated by topical 5-aminolevulinic acid seems to be a useful alternative in the onco-preventive management of oral leukoplakia lesions. However, it is recommendable to perform controlled and ran- domized clinical trials with homogeneous methodologies that allow the generation of a meta-analysis with a high level of evidence (AU)
Assuntos
Humanos , Masculino , Feminino , Fotoquimioterapia/métodos , Leucoplasia Oral/tratamento farmacológico , Ácido Aminolevulínico , Leucoplasia Oral/prevenção & controle , Resultado do Tratamento , Fármacos Fotossensibilizantes/uso terapêutico , Terapia a Laser/métodosRESUMO
O carcinoma epidermoide oral (CEO) é uma neoplasia maligna de patogenia complexa, já a displasia epitelial oral (DEO) é uma entidade que, na dependência de sua evolução, exibe riscos de transformação maligna para o CEO. A expressão alterada de genes supressores tumorais e proteínas reguladoras do ciclo celular apresentam relação com a etiopatogênese de diferentes cânceres. Entre os genes supressores tumorais destaca-se a família de inibidores de crescimento (inhibitor of growth - ING), que impedem o crescimento celular descontrolado. Dentre as proteínas reguladoras do ciclo celular podemos citar a Ciclina D1, que atua na progressão da fase S para a fase G1, permitindo a proliferação celular. O objetivo do presente estudo foi analisar a imunoexpressão das proteínas ING3 e Ciclina D1 em 28 espécimes de DEO e 25 de CEO localizados em língua, bem como avaliar morfologicamente e reclassificar as lesões segundo os critérios estabelecidos pela Organização Mundial da Saúde (OMS), além de modelo binário (Kujan et al. 2006), para DEO, e modelo buds-depth of invansion (BD) (Almagunsh et al. 2015) para CEO. A imunoexpressão das proteínas foi analisada de forma quantitativa, considerando a localização celular (citoplasmática e/ou nuclear para ING3 e nuclear para Ciclina D1) presentes no componente epitelial. A expressão das proteínas foi comparada entre os dois grupos de lesões, bem como com os parâmetros clínico-patológicos das lesões estudadas, através dos testes estatísticos Mann-Whitney (U) e teste de correlação de Spearman adotando um nível de significância de 5% para todos os testes considerando o valor de p ≤ 0,05. Dos 28 casos de DEO analisados 53,6% apresentaram-se como lesões de alto risco segundo o modelo binário, assim como dos 25 casos de CEO analisados foram considerados escores de alto risco (48%) de acordo com o modelo BD. Não foram encontradas associações estatisticamente significativas entre as variáveis morfológicas das lesões estudadas e as características clínicas (p>0,05). Com relação a expressão de Ciclina D1, esta foi significativamente maior em DEO quando comparada aos casos de CEO (p<0,05). A expressão de ING3 núcleo-citoplasmática foi significativamente menor nos casos de CEO, quando comparada aos casos de DEO (p<0,05), já a expressão de ING3, restrita ao citoplasma, foi maior nos casos de DEO, quando comparadas aos casos de CEO (p<0,05). Os resultados do presente estudo sugerem que a expressão das proteínas não tem relação com as gradações das lesões, porém, há notável diminuição da expressão nuclear de ING3 conforme a progressão maligna, indicando função supressora tumoral alterada desta proteína em DEO e CEOs. Destacamos, ainda, o aumento da expressão de Ciclina D1 em DEOs, mostrando que as lesões detêm uma taxa de proliferação celular significativa (AU).
Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of complex pathogenesis. In turn, oral epithelial dysplasia (OED) is an entity that, depending on its evolution, exhibits varied risks of malignant transformation to OSCC. The altered expression of tumor suppressor genes and cell cycle regulatory proteins are related to the etiopathogenesis of different malignant tumors. Among the tumor suppressor genes, the family of inhibitors of growth (ING) stands out, which prevents uncontrolled cell formation. Amid the cell cycle regulatory proteins, Cyclin D1 acts in the progression from S to G1 phase, allowing cell proliferation. The aim of the present study was to analyze the immunoexpression of ING3 and Cyclin D1 proteins in 28 OED and 25 OSCC specimens, located on the tongue, as well as to morphologically evaluate and to reclassify the lesions following the criteria established by World Health Organization (WHO) and the model proposed by Kujan et al. (2006), for OED; for OSCC, the system proposed by Almagunsh et al. (2015) was used. Protein immunoexpression was quantitatively evaluated, considering the cellular location (cytoplasmic and/or nuclear for ING3 and nuclear for Cyclin D1), present in the epithelial component. Protein expression was compared between the two groups of samples, as well as with the clinical-pathological parameters of the lesions studied, through the Mann-Whitney (U) statistical tests and the Spearman correlation test, adopting a significance level of 5% for all tests considering the value of p≤ 0.05. Of the 28 cases of OED analyzed, 53.6% were high-risk lesions according to the binary model and of the 25 cases of OSCC analyzed, 48% were considered high-risk scores according to the BD model. No statistically significant associations were found between the morphological variables of the lesions studied and the clinical characteristics (p>0.05). A statistically significant difference was observed between the absence of ING3 expression and the grading of OEDs, according to the WHO (p<0.05). Regarding the expression of Cyclin D1, it was significantly higher in OED, when compared to OSCC cases (p<0.05). Nucleocytoplasmic ING3 expression was significantly lower in OSCC cases when compared to OED cases (p<0.05). Cytoplasm-restricted ING3 expression was higher in OED cases when compared to OSCC cases (p<0.05). The results of the present study suggest that, although there is no evidence of a significant relationship between the expression of proteins and the histopathological gradations of the lesions, there is a notable decrease in the nuclear expression of ING3, with an increase in the severity of the lesions, indicating an altered tumor suppressor function of this protein in OED and OSCCs. We also highlight the increased expression of Cyclin D1 in OEDs, showing that these lesions have a significant rate of cell proliferation (AU).
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Biomarcadores Tumorais , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/patologia , Leucoplasia Oral/patologia , Imuno-Histoquímica , Estatísticas não ParamétricasRESUMO
RESUMEN Fundamento la leucoplasia es la lesión potencialmente maligna más frecuente en las membranas mucosas de la boca y se puede presentar con diferentes grados de displasia epitelial. El estudio histológico de esta lesión unido a la medición de parámetros morfométricos y estereológicos, permite la mejor comprensión de procesos tanto fisiológicos como patológicos. Objetivo: caracterizar los parámetros histomorfométricos de la mucosa bucal en pacientes portadores de leucoplasia bucal según grado de displasia epitelial. Método: se realizó un estudio de serie de casos, con el objeto de determinar indicadores morfométricos, de lesiones leucoplásicas de la mucosa oral en biopsias de pacientes atendidos en los Servicios de Anatomía Patológica y Maxilofacial del Hospital General Universitario Dr. Gustavo Aldereguía Lima, de la provincia Cienfuegos. La muestra se obtuvo por muestreo intencionado, la cual quedó constituida por 30 láminas histológicas (biopsias), distribuidas en tres grupos de diez láminas por cada grado de displasia epitelial. La variable de estudio fue la caracterización morfométrica de la leucoplasia de la mucosa oral con displasia. Se aplicó estadística descriptiva e inferencial. Resultados: predominaron tres parámetros en la clasificación de la displasia: alteración de los clavos interpapilares, hiperplasia y pérdida de la polaridad de las células basales. Se constató presencia de ortoparaqueratosis, epitelios hiperplásicos e infiltrado inflamatorio del corion, en más de la mitad de los casos. Hubo significación estadística en las relaciones que se establecieron entre la altura o profundidad de las papilas y la densidad relativa de células según grado de displasia epitelial, al aplicar la estadística inferencial. Conclusiones: predominaron tres parámetros en la clasificación de la displasia. Se constató presencia de ortoparaqueratosis, epitelios hiperplásicos e infiltrado inflamatorio del corion, en más de la mitad de los casos.
ABSTRACT Background: leukoplakia is the most frequent potentially malignant lesion in the mucous membranes of the mouth and can present with different degrees of epithelial dysplasia. The histological study of this lesion, together with the measurement of morphometric and stereological parameters, allows a better understanding of both physiological and pathological processes. Objective: to characterize the histomorphometric parameters of the oral mucosa in patients with oral leukoplakia according to the degree of epithelial dysplasia. Method: a case series study was carried out in order to determine morphometric indicators of leukoplastic lesions of the oral mucosa in biopsies of patients treated at the Pathology and Maxillofacial Anatomy services of the Dr. Gustavo Aldereguía Lima General University Hospital, in Cienfuegos province. The sample was obtained by intentional sampling, which was made up of 30 histological slides (biopsies), distributed in three groups of ten slides for each degree of epithelial dysplasia. The study variable was the morphometric characterization of oral mucosal leukoplakia with dysplasia. Descriptive and inferential statistics were applied. Results: three parameters prevailed in the classification of dysplasia: alteration of the interpapillary nails, hyperplasia and loss of polarity of the basal cells. The presence of orthoparakeratosis, hyperplastic epithelia and inflammatory infiltrate of the chorion was confirmed in more than half of the cases. There was statistical significance in the relationships established between the height or depth of the papillae and the relative density of cells according to the degree of epithelial dysplasia, when applying inferential statistics. Conclusions: three parameters predominated in the classification of dysplasia. The presence of orthoparakeratosis, hyperplastic epithelia and inflammatory infiltrate of the chorion was confirmed in more than half of the cases.