ABSTRACT
This systematic review aims to determine whether the presence of human papillomavirus (HPV) influences the immunohistochemical expression of programmed cell death-1 ligand (PD-L1) in oropharyngeal squamous cell carcinoma (OPSCC). PD-L1 immunohistochemical expression varies in OPSCC, and the presence of HPV is a plausible explanation for this variability. Comprehending these findings is crucial, as high PD-L1 expression in the tumor microenvironment of OPSCC can help identify patient subgroups that could be suitable for immunotherapy. Therefore, a systematic review was conducted following PRISMA guidelines (CRD42023437800). An electronic literature search was performed without time or language restrictions. The search included PubMed/MEDLINE, Embase, Scopus, Web of Science, https://clinictrials.gov, and relevant journals. A meta-analysis was performed using RStudio. Fourteen studies involving 1,629 participants were included. The sample consisted predominantly of males (81.26%) with a mean age of 58.3 years. Concerning clinical and pathological characteristics, the most frequently described anatomical location was the tonsils (68.54%), and most participants were either current or former smokers (78%) and alcohol users (79%). Advanced TNM IV was the most common stage. Regarding histopathological characteristics, HPV 16 was the only type mentioned, and half of the cases were detected through immunohistochemistry. The SP142 clone (35.7%) and the pattern of membrane immunostaining in tumor cells (71%) were the most commonly employed methods. The most prevalent findings were positive expression of PD-L1 (64.28%) and negative HPV status (57.14%). The association between PD-L1 positivity and HPV positivity (78.57%) was confirmed by meta-analysis. The conclusion was that HPV-positive status has an impact on immunohistochemical expression of PD-L1 in OPSCC.
Subject(s)
B7-H1 Antigen , Carcinoma, Squamous Cell , Immunohistochemistry , Oropharyngeal Neoplasms , Papillomavirus Infections , Humans , B7-H1 Antigen/analysis , Oropharyngeal Neoplasms/virology , Oropharyngeal Neoplasms/pathology , Papillomavirus Infections/complications , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Male , Female , Carcinoma, Squamous Cell/virology , Carcinoma, Squamous Cell/pathology , Middle Aged , Biomarkers, Tumor/analysis , PapillomaviridaeABSTRACT
BACKGROUND: This retrospective study investigates the clinicopathological features and outcomes of young and elderly patients diagnosed with lip squamous cell carcinoma (LSCC). MATERIAL AND METHODS: Data from LSCC patients from Dr. Luiz Antonio Hospital in Natal, Brazil (2000-2015) were analyzed, grouping individuals below 40 and above 60 years old. Demographics, lifestyle habits, clinicopathologic characteristics, and treatment outcomes were examined using descriptive statistics, Chi-square and Fisher's tests, and Kaplan-Meier survival analysis. RESULTS: A total of 47 patients was analyzed, being 20 younger and 27 older, finding significant age-related differences (p = < 0.0001). Although in both groups the tumor was more common in males, older patients had a higher rate of females (29.6%) (p=0.0358) and smoking (70.4%) (p = 0.0043) and underwent more modalities of treatments (p = 0.0027). There were no significant differences in the other analyzed clinicopathologic factors, and survival rates did not differ significantly, though younger patients showed slightly better survival metrics in univariate analysis. CONCLUSIONS: LSCC exhibits some distinct clinicopathological features across different age groups, with significant differences in treatment modalities and progression rates. Age-specific approaches may be required to optimize treatment outcomes.
Subject(s)
Carcinoma, Squamous Cell , Lip Neoplasms , Humans , Retrospective Studies , Male , Female , Middle Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Adult , Lip Neoplasms/pathology , Lip Neoplasms/mortality , Age Factors , Aged , Aged, 80 and over , Young Adult , Survival RateABSTRACT
PURPOSE: Evaluate the immunohistochemical expression of the ING3 in actinic cheilitis and squamous cell carcinoma of the lower lip. METHODS: Forty-five specimens of actinic cheilitis and 48 specimens of squamous cell carcinoma of the lower lip were submitted to immunohistochemical detection of ING3. The protein expression in different cellular sublocations was compared between the two groups, and associations with the clinicopathological variables were analyzed. A significance level of 5% was adopted for all tests. RESULTS: Deaths were significantly more frequent in tumors with a high histopathological risk score (p < 0.05). In actinic cheilitis, significant differences were found in the nucleus-cytoplasmic expression of ING3 and expression restricted to the cytoplasm with binary histopathological grading (p < 0.05). In squamous cell carcinoma of the lower lip, there was no statistically significant difference when comparing ING3 expressions with clinical and morphological parameters (p > 0.05). Nucleo-cytoplasmic ING3 expression was significantly lower in squamous cell carcinoma of the lower lip when compared to actinic cheilitis (p < 0.05) and the expression restricted to the cytoplasm was significantly higher in squamous cell carcinoma of the lower lip (p < 0.05). CONCLUSION: The results of this study suggest that there is a marked decrease in the nuclear expression of ING3 as malignant progression occurs, indicating an impaired tumor suppressor function of this protein in actinic cheilitis and squamous cell carcinoma of the lower lip.
Subject(s)
Cell Nucleus , Cheilitis , Homeodomain Proteins , Lip Neoplasms , Tumor Suppressor Proteins , Humans , Lip Neoplasms/pathology , Lip Neoplasms/metabolism , Cheilitis/pathology , Cheilitis/metabolism , Tumor Suppressor Proteins/biosynthesis , Female , Middle Aged , Male , Aged , Homeodomain Proteins/biosynthesis , Homeodomain Proteins/metabolism , Adult , Cell Nucleus/metabolism , Cell Nucleus/pathology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Carcinogenesis , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Immunohistochemistry , Aged, 80 and overABSTRACT
The oral cavity is a frequent site for head and neck cancers, which rank as the sixth most common cancer globally, with a 5-year survival rate slightly over 50%. Current treatments are limited, and resistance to therapy remains a significant clinical obstacle. IsCT1, a membrane-active peptide derived from the venom of the scorpion Opisthacanthus madagascariensis, has shown antitumor effects in various cancer cell lines, including breast cancer and chronic myeloid leukemia. However, its hemolytic action limits its potential therapeutic use. This study aims to assess the antitumor and antiproliferative activities of synthetic peptides derived from IsCT1 (IsCT-P, AC-AFPK-IsCT1, AFPK-IsCT1, AC-KKK-IsCT1, and KKK-IsCT1) in the context of oral squamous cell carcinoma. We evaluated the cytotoxic effects of these peptides on tongue squamous cell carcinoma cells and normal cells, as well as their impact on cell cycle phases, the expression of proliferation markers, modulators of cell death pathways, and mitochondrial potential. Our results indicate that the IsCT1 derivatives IsCT-P and AC-AFPK-IsCT1 possess cytotoxic properties towards squamous cell carcinoma cells, reducing mitochondrial membrane potential and the proliferative index. The treatment of cancer cells with AC-AFPK-IsCT1 led to a positive modulation of pro-apoptotic markers p53 and caspases 3 and 8, a decrease in PCNA and Cyclin D1 expression, and cell cycle arrest in the S phase. Notably, contrary to the parental IsCT1 peptide, AC-AFPK-IsCT1 did not exhibit hemolytic activity or cytotoxicity towards normal cells. Therefore, AC-AFPK-IsCT1 might be a viable therapeutic option for head and neck cancer treatment.
Subject(s)
Antineoplastic Agents , Carcinoma, Squamous Cell , Cell Proliferation , Mouth Neoplasms , Scorpion Venoms , Humans , Cell Proliferation/drug effects , Cell Line, Tumor , Mouth Neoplasms/drug therapy , Mouth Neoplasms/pathology , Scorpion Venoms/pharmacology , Scorpion Venoms/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Animals , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Peptides/pharmacology , Peptides/chemistry , Peptides/chemical synthesis , Apoptosis/drug effects , Scorpions/chemistry , Membrane Potential, Mitochondrial/drug effects , Cell Cycle/drug effectsABSTRACT
Head and neck squamous cell carcinoma (H&NSCC) is an anatomic, biological, and genetic complex disease. It involves more than 1000 genes implied in its oncogenesis; for this review, we limit our search and description to the genes implied in the onco-ontogeny of the derivates from the first pharyngeal arch during embryo development. They can be grouped as transcription factors and signaling molecules (that act as growth factors that bind to receptors). Finally, we propose the term embryo-oncogenesis to refer to the activation, reactivation, and use of the genes involved in the embryo's development during the oncogenesis or malignant tumor invasion and metastasis events as part of an onco-ontogenic inverse process.
Subject(s)
Branchial Region , Humans , Branchial Region/metabolism , Branchial Region/pathology , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Animals , Carcinogenesis/genetics , Carcinogenesis/pathology , Gene Expression Regulation, Neoplastic , Signal TransductionABSTRACT
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.
Subject(s)
Apoptosis , Artemisinins , Cell Movement , Cisplatin , Disease Progression , Leukoplakia, Oral , Mouth Neoplasms , Artemisinins/pharmacology , Animals , Leukoplakia, Oral/pathology , Leukoplakia, Oral/drug therapy , Humans , Cisplatin/pharmacology , Mice , Mouth Neoplasms/pathology , Mouth Neoplasms/drug therapy , Apoptosis/drug effects , Cell Movement/drug effects , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , HMGB1 Protein/metabolism , Antineoplastic Agents/pharmacologyABSTRACT
A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.
Subject(s)
Corneal Transplantation , Mitomycin , Humans , Mitomycin/therapeutic use , Corneal Transplantation/methods , Corneal Diseases/surgery , Corneal Diseases/drug therapy , Eye Neoplasms/surgery , Eye Neoplasms/drug therapy , Eye Neoplasms/pathology , Treatment Outcome , Male , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/drug therapy , Female , Middle Aged , Antibiotics, Antineoplastic/therapeutic useABSTRACT
Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancers, known for its aggressiveness and poor prognosis. Photodynamic therapy (PDT) has emerged as a promising adjuvant therapy and is linked to immunogenic cell death, activating innate and adaptive anti-tumor responses. Natural Killer (NK) cells, key players in malignant cell elimination, have not been extensively studied in PDT. This study evaluates whether PDT increases OSCC cell lines' susceptibility to NK cell cytotoxicity. PDT, using 5-aminolevulinic acid (5-ALA) and LED irradiation, was applied to Ca1 and Luc4 cell lines. Results showed a dose-dependent viability decrease post-PDT. Gene expression analysis revealed upregulation of NK cell-activating ligands (ULBP1-4, MICA/B) and decreased MHC class I expression in Ca1, suggesting increased NK cell susceptibility. Enhanced NK cell cytotoxicity was confirmed in Ca1 but not in Luc4 cells. These findings indicate that PDT may enhance NK cell-mediated cytotoxicity in OSCC, offering potential for improved treatment strategies.
Subject(s)
Aminolevulinic Acid , Carcinoma, Squamous Cell , Killer Cells, Natural , Mouth Neoplasms , Photochemotherapy , Humans , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Mouth Neoplasms/pathology , Mouth Neoplasms/drug therapy , Mouth Neoplasms/immunology , Cell Line, Tumor , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/immunology , Aminolevulinic Acid/pharmacology , Cell Survival/drug effects , Cell Survival/radiation effects , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/radiation effects , Cytotoxicity, Immunologic/drug effectsABSTRACT
OBJECTIVE: Cancer genomics and transcriptomics studies have provided a large volume of data that enables to test of hypotheses based on real data from cancer patients. Ezrin (encoded by the EZR gene) is a highly expressed protein in cancer that contributes to linking the actin cytoskeleton to the cell membrane and signal transduction pathways involved in oncogenesis and disease progression. NSC305787 is a pharmacological ezrin inhibitor with potential antineoplastic effects. In the present study, the authors prospected EZR mRNA levels in a pan-cancer analysis and identified potential cancers that could benefit from anti-EZR therapies. METHODS: This study analyzed TCGA data for 32 cancer types, emphasizing cervical squamous cell carcinoma and stomach adenocarcinoma. It investigated the impact of EZR transcript levels on clinical outcomes and identified differentially expressed genes. Cell lines were treated with NSC305787, and its effects were assessed through various cellular and molecular assays. RESULTS: EZR mRNA levels are highly expressed, and their expression is associated with biologically relevant molecular processes in cervical squamous carcinoma and stomach adenocarcinoma. In cellular models of cervical and gastric cancer, NSC305787 reduces cell viability and clonal growth (p < 0.05). Molecular analyses indicate that the pharmacological inhibition of EZR induces molecular markers of cell death and DNA damage, in addition, to promoting the expression of genes associated with apoptosis and inhibiting the expression of genes related to survival and proliferation. CONCLUSION: The present findings provide promising evidence that ezrin may be a molecular target in the treatment of cervical and gastric carcinoma.
Subject(s)
Adenocarcinoma , Cytoskeletal Proteins , Gene Expression Profiling , Stomach Neoplasms , Uterine Cervical Neoplasms , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , Cytoskeletal Proteins/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/metabolism , Cell Line, Tumor , Female , Adenocarcinoma/genetics , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Gene Expression Regulation, Neoplastic/drug effects , RNA, Messenger , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Proliferation/drug effects , Cell Proliferation/genetics , Cell Survival/drug effects , Apoptosis/drug effects , Apoptosis/geneticsABSTRACT
Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy linked to high-risk human papillomavirus (HPV) infection, which develops from precursor lesions like low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions (HGSILs). ASCC incidence varies across populations and poses increased risk for people living with HIV. Our investigation focused on transcriptomic and metatranscriptomic changes from squamous intraepithelial lesions to ASCC. Metatranscriptomic analysis highlighted specific bacterial species (e.g., Fusobacterium nucleatum, Bacteroides fragilis) more prevalent in ASCC than precancerous lesions. These species correlated with gene-encoding enzymes (Acca, glyQ, eno, pgk, por) and oncoproteins (FadA, dnaK), presenting potential diagnostic or treatment markers. Unsupervised transcriptomic analysis identified distinct sample clusters reflecting histological diagnosis, immune infiltrate, HIV/HPV status, and pathway activities, recapitulating anal cancer progression's natural history. Our study unveiled molecular mechanisms in anal cancer progression, aiding in stratifying HGSIL cases based on low or high risk of progression to malignancy.
Subject(s)
Anus Neoplasms , Carcinoma, Squamous Cell , Transcriptome , Humans , Anus Neoplasms/genetics , Anus Neoplasms/immunology , Anus Neoplasms/pathology , Anus Neoplasms/virology , Anus Neoplasms/microbiology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/microbiology , Carcinoma, Squamous Cell/pathology , Microbiota/immunology , Male , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Papillomavirus Infections/virology , Papillomavirus Infections/immunology , Squamous Intraepithelial Lesions/genetics , Squamous Intraepithelial Lesions/pathology , Squamous Intraepithelial Lesions/virology , Female , Disease Progression , Middle Aged , HIV Infections/complications , HIV Infections/immunologyABSTRACT
BACKGROUND: Documentation of lingual tumors is scarce in nonhuman primates. METHODS: Through a multi-institutional retrospective study we compile cases of primary and metastatic neoplasia in non-human primates. RESULTS: We describe five cases of lingual neoplasia. Three cases are primary lingual tumors: chondro-osteoblastic lipoma in a howler monkey, squamous cell carcinoma, and fibroma in two baboons. We describe two cases of metastatic lymphoma in the tongue in rhesus macaques. A literature review of published lingual neoplasia in nonhuman primates is included in this manuscript. CONCLUSION: Lingual neoplasia is seldom reported in non-human primates.
Subject(s)
Monkey Diseases , Papio , Tongue Neoplasms , Animals , Monkey Diseases/pathology , Monkey Diseases/diagnosis , Male , Female , Tongue Neoplasms/pathology , Tongue Neoplasms/veterinary , Tongue Neoplasms/diagnosis , Retrospective Studies , Macaca mulatta , Carcinoma, Squamous Cell/veterinary , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/diagnosis , Lipoma/veterinary , Lipoma/pathology , Lipoma/diagnosisABSTRACT
3D in vitro systems offer advantages over the shortcomings of two-dimensional models by simulating the morphological and functional features of in vivo-like environments, such as cell-cell and cell-extracellular matrix interactions, as well as the co-culture of different cell types. Nevertheless, these systems present technical challenges that limit their potential in cancer research requiring cell line- and culture-dependent standardization. This protocol details the use of a magnetic 3D bioprinting method and other associated techniques (cytotoxicity assay and histological analysis) using oral squamous cell carcinoma cell line, HSC3, which offer advantages compared to existing widely used approaches. This protocol is particularly timely, as it validates magnetic bioprinting as a method for the rapid deployment of 3D cultures as a tool for compound screening and development of heterotypic cultures such as co-culture of oral squamous cell carcinoma cells with cancer-associated fibroblasts (HSC3/CAFs).
Subject(s)
Bioprinting , Carcinoma, Squamous Cell , Coculture Techniques , Mouth Neoplasms , Printing, Three-Dimensional , Spheroids, Cellular , Humans , Mouth Neoplasms/pathology , Bioprinting/methods , Cell Line, Tumor , Carcinoma, Squamous Cell/pathology , Coculture Techniques/methods , Spheroids, Cellular/pathology , Cell Culture Techniques, Three Dimensional/methodsSubject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Esophagoscopy , Humans , Esophageal Neoplasms/therapy , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Esophageal Neoplasms/diagnostic imaging , Esophageal Squamous Cell Carcinoma/therapy , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/diagnosis , Esophagoscopy/methods , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathologyABSTRACT
OBJECTIVE: Treating aggressive superficial squamous cell carcinoma (SCC) poses challenges due to invasiveness. Palliative care is recommended for inoperable cases with extensive tumors near vital organs, risking disfigurement or functional impairment. Electrochemotherapy (ECT) is an emerging cutaneous tumor treatment, but its efficacy against superficial SCC remains uncertain. This study conducts a systematic review and single-arm meta-analysis to evaluate ECT's effectiveness against superficial SCC and provide current evidence for clinical practice. METHODS: Embase, PubMed and Cochrane Library were searched for studies up to May 2023. The random effects model analyzed complete response (CR) and partial response (PR), with subgroup assessment based on drug dosage, treatment response evaluation, tumor size, primary/recurrent status, and tumor location. RESULTS: Ten studies involving 162 patients and 208 tumors were included. Pooled CR and PR rates for ECT-treated superficial SCC were 66.5% (95% CI 48.4%-82.5%; I2 = 84%) and 20.3% (95% CI 10.5%-32.3%; I2 = 70%), respectively. Subgroup analysis indicated ECT's superiority in treating primary tumors (PR: 70%, CR: 30%) and tumors ≤ 3 cm (PR: 81.3%, CR: 10.1%) compared to recurrent tumors (PR: 56.7%, CR: 36.5%) and tumors > 3 cm (PR: 45.2%, CR: 34.4%). CONCLUSION: This single-arm meta-analysis confirms ECT's efficacy against superficial SCC, especially in primary tumors and those ≤ 3 cm in diameter. The study highlights the impact of tumor location and response evaluation on ECT's benefits, warranting further investigation through additional research.
Subject(s)
Carcinoma, Squamous Cell , Electrochemotherapy , Skin Neoplasms , Humans , Electrochemotherapy/methods , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Treatment OutcomeABSTRACT
Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.
Subject(s)
Mouth Neoplasms , Proteome , Saliva , Humans , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Mouth Neoplasms/diagnosis , Saliva/chemistry , Saliva/metabolism , Proteome/analysis , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/diagnosis , Female , Biomarkers, Tumor/metabolism , Male , Lymphatic Metastasis , Protein Conformation , Middle Aged , Prognosis , Proteomics/methods , Transketolase/metabolism , Aged , Mass Spectrometry , Salivary Proteins and Peptides/metabolism , Salivary Proteins and Peptides/analysisABSTRACT
Identifying marker combinations for robust prognostic validation in primary tumour compartments remains challenging. We aimed to assess the prognostic significance of CSC markers (ALDH1, CD44, p75NTR, BMI-1) and E-cadherin biomarkers in OSCC. We analysed 94 primary OSCC and 67 metastatic lymph node samples, including central and invasive tumour fronts (ITF), along with clinicopathological data. We observed an increase in ALDH1+/CD44+/BMI-1- tumour cells in metastatic lesions compared to primary tumours. Multivariate analysis highlighted that elevated p75NTR levels (at ITF) and reduced E-cadherin expression (at the tumour centre) independently predicted metastasis, whilst ALDH1high exhibited independent predictive lower survival at the ITF, surpassing the efficacy of traditional tumour staging. Then, specifically at the ITF, profiles characterized by CSChighE-cadherinlow (ALDH1highp75NTRhighE-cadherinlow) and CSCintermediateE-cadherinlow (ALDH1 or p75NTRhighE-cadherinlow) were significantly associated with worsened overall survival and increased likelihood of metastasis in OSCC patients. In summary, our study revealed diverse tumour cell profiles in OSCC tissues, with varying CSC and E-cadherin marker patterns across primary tumours and metastatic sites. Given the pivotal role of reduced survival rates as an indicator of unfavourable prognosis, the immunohistochemistry profile identified as CSChighE-cadherinlow at the ITF of primary tumours, emerges as a preferred prognostic marker closely linked to adverse outcomes in OSCC.
Subject(s)
Aldehyde Dehydrogenase 1 Family , Biomarkers, Tumor , Cadherins , Carcinoma, Squamous Cell , Mouth Neoplasms , Adult , Aged , Female , Humans , Male , Middle Aged , Aldehyde Dehydrogenase 1 Family/metabolism , Biomarkers, Tumor/metabolism , Cadherins/metabolism , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Hyaluronan Receptors/metabolism , Immunohistochemistry , Lymphatic Metastasis , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/mortality , Mouth Neoplasms/diagnosis , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Nerve Tissue Proteins/metabolism , Polycomb Repressive Complex 1/metabolism , Polycomb Repressive Complex 1/genetics , Prognosis , Receptors, Nerve Growth Factor/metabolism , Retinal Dehydrogenase/metabolismABSTRACT
BACKGROUND: To describe demographic and clinicopathological aspects of a South-American cohort of incipient oral squamous cell carcinoma patients. MATERIAL AND METHODS: A cross-sectional, observational study was performed to assess demographic and clinicopathological characteristics of incipient oral squamous cell carcinoma patients from 6 South-American institutions. RESULTS: One hundred and seven patients within the histopathological spectrum of incipient oral squamous cell carcinoma (in-situ and microinvasive) were included. Fifty-eight (54.2%) patients were men with a mean age of 60.69 years. Forty-nine (45.8%) and thirty-nine (36.5%) patients had history of tobacco and alcohol use, respectively. Clinically, most of the lesions were plaques (82.2%), ≥ 2 cm in extension (72%), affecting the lateral border of the tongue (55.1%), and soft palate (12.1%) with a mixed (white and red) appearance. Eighty-two (76.7%) lesions were predominantly white and 25 (23.3%) predominantly red. CONCLUSIONS: To the best of our knowledge, this is the largest cohort of incipient oral squamous cell carcinoma patients, which raises awareness of clinicians' inspection acuteness by demonstrating the most frequent clinical aspects of this disease, potentially improving oral cancer secondary prevention strategies.
Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Humans , Male , Cross-Sectional Studies , Mouth Neoplasms/epidemiology , Mouth Neoplasms/pathology , Middle Aged , Female , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Aged , South America/epidemiology , Aged, 80 and over , AdultABSTRACT
BACKGROUND: The lips are the transition zone between the facial skin and the oral mucosa and are the site of alterations related to a broad spectrum of etiologies. Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most prevalent neoplasms affecting lips. This study evaluated the demographic and clinicopathological features of the SCC and BCC in the lip. MATERIAL AND METHODS: A retrospective cross-sectional descriptive study (1994-2019) was carried out. Demographic and clinicopathologic data were collected from a hospital's dermatological service and an oncologic hospital. The data were submitted to descriptive analysis and Pearson's chi-square and Fisher's exact tests (p ≤ 0.05). RESULTS: 417 medical records were analyzed, of which 323 corresponded to SCC (77.5%) and 94 to BCC (22.5%). SCC showed more frequency in males (58.8%) and BCC in females (54.3%). The lower lip was significantly affected in male patients (p < 0.0001) and by both neoplasms (70.6% and 56.4%, respectively; p = 0.014). SCC and BCC were mainly treated with surgery (88.3% and 93.2%, respectively). Surgical margin was frequently negative in SCC and BCC (87%; 72.3%, respectively), and no recurrence was observed in 79.9% of SCC and 69.1% of BCC cases. CONCLUSIONS: SCC was more frequent in male patients, while BCC showed more frequency in female patients. Both neoplasms mainly affect the lower lip. Understanding the epidemiological profile of these lesions in the lip, as well as their etiology and clinical features, is fundamental for appropriate clinical conduct and the creation and/or amplification of preventive measures.