RESUMO
Adenoid cystic carcinoma (ACC) and basal cell adenoma (BCA) share many histological characteristics and often need a differential diagnosis in clinical pathology. Recently, we found homeobox protein engrailed-1 (EN1) was a potential diagnostic marker for ACC in an organoids library of salivary gland tumors (SGTs). Here we aim to confirm EN1 as a differential diagnostic marker for ACC, and further investigate the regulatory mechanism and biological function of EN1 in tumor progression. The transcriptional analysis, quantitative polymerase chain reaction, Western blot and immunohistochemistry staining were performed and revealed that EN1 was specifically and highly expressed in ACC, and accurately differentiated ACC from BCA. Furthermore, TGFß signaling pathway was found associated with ACC, and the regulation of EN1 through TGFß was detected in the human ACC cell lines and patient-derived organoids (PDOs). TGFß-induced EN1 was important in promoting tumor budding in the PDOs model. Interestingly, a high level of EN1 and TGFß1 in the budding tips was observed in ACC clinical samples, and the expression of EN1 and TGFß1 in ACC was significantly associated with the clinical stage. In summary, our study verified EN1 is a good diagnostic marker to differentiate ACC from BCA. TGFß-induced EN1 facilitates the tumor budding of ACC, which might be an important mechanism related to the malignant phenotype of ACC.
Assuntos
Adenoma , Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Humanos , Adenoma/patologia , Biomarcadores Tumorais/genética , Carcinoma Adenoide Cístico/patologia , Proteínas de Homeodomínio , Neoplasias das Glândulas Salivares/patologia , Fator de Crescimento Transformador betaRESUMO
Tumors of the major and minor salivary glands histologically encompass a diverse and partly overlapping spectrum of frequent diagnostically challenging neoplasms. Despite recent advances in molecular testing and the identification of tumor-specific mutations or gene fusions, there is an unmet need to identify additional diagnostic biomarkers for entities lacking specific alterations. In this study, we collected a comprehensive cohort of 363 cases encompassing 20 different salivary gland tumor entities and explored the potential of DNA methylation to classify these tumors. We were able to show that most entities show specific epigenetic signatures and present a machine learning algorithm that achieved a mean balanced accuracy of 0.991. Of note, we showed that cribriform adenocarcinoma is epigenetically distinct from classical polymorphous adenocarcinoma, which could support risk stratification of these tumors. Myoepithelioma and pleomorphic adenoma form a uniform epigenetic class, supporting the theory of a single entity with a broad but continuous morphologic spectrum. Furthermore, we identified a histomorphologically heterogeneous but epigenetically distinct class that could represent a novel tumor entity. In conclusion, our study provides a comprehensive resource of the DNA methylation landscape of salivary gland tumors. Our data provide novel insight into disputed entities and show the potential of DNA methylation to identify new tumor classes. Furthermore, in future, our machine learning classifier could support the histopathologic diagnosis of salivary gland tumors.
RESUMO
Primary pulmonary salivary gland tumors (PSGT) constitute a rare subtype of non-small cell lung cancer (NSCLC). Currently, no established treatment guidelines exist for advanced PSGT. The efficacy of platinum-based chemotherapy for PSGT within the context of NSCLC remains uncertain. Therefore, we retrospectively collected 37 PSGT patients who underwent first-line platinum-based chemotherapy from 2010 to 2023. Survival analysis, employing the Kaplan-Meier method, and group comparisons via the log rank test were conducted. Our results show that first-line platinum-based chemotherapy demonstrates favorable efficacy and manageable safety in advanced PSGT, with the combination of Paclitaxel + Platinum emerging as a preferred option.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pulmonares , Paclitaxel , Neoplasias das Glândulas Salivares , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/tratamento farmacológico , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Adulto , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Salivary gland tumors (SGTs) are a heterogenous group of pathologies, which still represents a challenge regarding differential diagnosis and therapy. Although histological findings govern SGTs management, detection of molecular alterations is emerging as an effective additional tool. The aim of this study was to analyze the relative expression levels of three micro RNAs (miR-26a, miR-26b, and miR-191), and three pro-oncogenic molecular markers (PLAG1, MTDH, and HIF2) in SGTs and normal salivary gland (NSG) tissues and evaluate them as potential differential diagnosis markers. METHODS: This cross-sectional study included 58 patients with SGTs (23 pleomorphic adenomas, 27 Warthin tumors, and 8 malignant SGTs) and 10 controls (normal salivary gland tissues). Relative gene expression levels of all investigated molecules were determined by reverse transcriptase-real-time polymerase chain reaction. RESULTS: All three micro RNAs exhibited highest expression levels in benign SGTs, whereas miR-26a And miR-191 were significantly more expressed in PAs compared to WTs (p = 0.045 and p = 0.029, respectively). PLAG1 And HIF2 were both overexpressed in WTs compared to PAs (p = 0.048 and p = 0.053, respectively). Bioinformatic analysis suggested that all investigated micro RNAs function as negative regulators of MTDH. CONCLUSION: The results of this study suggest that all three micro RNAs have a considerable negative impact on MTDH oncogene expression in malignant tumors, while the differences between levels of miR-26a, miR-191, PLAG1, and HIF2 in PA and WT represent possible differential diagnosis markers.
Assuntos
Adenolinfoma , Adenoma Pleomorfo , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Proteínas de Ligação a DNA , Regulação para Baixo , Proteínas de Membrana , MicroRNAs , Neoplasias das Glândulas Salivares , Regulação para Cima , Humanos , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/metabolismo , Masculino , Adenoma Pleomorfo/genética , Adenoma Pleomorfo/patologia , Adenoma Pleomorfo/metabolismo , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Adenolinfoma/patologia , Adenolinfoma/genética , Idoso , Adulto , Biomarcadores Tumorais , Proteínas de Ligação a RNA , Diagnóstico Diferencial , Regulação Neoplásica da Expressão Gênica , Idoso de 80 Anos ou maisRESUMO
Parotid tumors present a wide range of histological features, from benign to malignant. Periostin, an extracellular matrix protein specifically expressed in the periosteum and periodontal ligament, is isolated from osteoblast cell lines. It regulates fibrosis and collagen deposition and plays an important role in myocardial repair after myocardial infarction. It is also known to be involved in otorhinolaryngological-diseases. This study included 36 patients [38 specimens; 16 men and 20 women, mean age 59.2 (range 26-82) years] who underwent parotid tumor resection at the Division of Otorhinolaryngology, Tohoku Medical and Pharmaceutical University, between April 2017 and March 2022 and were clinically and pathologically diagnosed as having benign parotid tumors. Formalin-fixed, paraffin-embedded sections from the surgical specimens were autoclaved and immunostained with anti-periostin antibodies to evaluate the expression and distribution of periostin. Histologically, the tumors were diagnosed as pleomorphic adenomas in 15 cases (15 specimens), Warthin's tumors in 13 cases (15 specimens), basal cell adenomas in 2 cases (2 specimens), oncocytomas in 4 cases (4 specimens), and myoepitheliomas in 2 cases (2 specimens). An increased expression of periostin was found in 32 of 38 samples (84.2%) in the stroma of benign parotid tumors. Four distinct patterns of periostin expression were observed in benign parotid gland tumors: negative, superficial, infiltrative, and diffuse. Statistically significant differences were found between periostin expression patterns and histological classification of the tumors. Our results suggest that periostin may be involved in the pathogenesis of benign parotid tumors and could serve as a new biomarker for these tumors.
Assuntos
Adenoma Pleomorfo , Adenoma , Neoplasias Parotídeas , Neoplasias das Glândulas Salivares , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenoma/metabolismo , Adenoma Pleomorfo/metabolismo , Adenoma Pleomorfo/patologia , Neoplasias Parotídeas/metabolismo , Neoplasias Parotídeas/patologia , Periostina , Neoplasias das Glândulas Salivares/metabolismoRESUMO
OBJECTIVES: The purpose of this review was to present the basic concepts of metabolomics methodology and the use of saliva for diagnostic, prognostic, and predictive strategies. MATERIAL AND METHODS: This review followed the focus in: "saliva metabolomics" and "oral diseases". The authors searched studies on PubMed database. The inclusion criteria were original studies and reviews that assessed metabolomics techniques. A descriptive analysis was performed considering the study design, approach system, clinical steps, and tools for the determination of profile or biomarkers metabolites, and the advantages and disadvantages. RESULTS: Metabolomic analyses use a combination of analytical instrumentation and informatic tools to provide information on metabolite characteristics. In this review we described different technologies applied and the advantages and limitations of each technique. Furthermore, in the literature search, we retrieved 25 studies that investigated saliva metabolites in oral diseases: 8 studies used targeted analysis and 17 untargeted metabolomics approaches. Most studies included patients with periodontal diseases, oral squamous cell carcinoma, and Sjögren Syndrome. The most frequently reported metabolites were glycine, leucine, phenylalanine, dipeptides, linoleic acid, arachidonic acid, tyrosine, choline, taurine, lactate, valine, and proline. CONCLUSIONS: Metabolomics analysis has emerged as a powerful tool for tumor diagnosis and to enhance tumor classification, including salivary gland tumors (SGTs). It also holds promise for developing personalized treatment plans and defining more precise prognostic categories. CLINICAL RELEVANCE: Metabolomics is the most functional and comprehensive technique for monitoring and understanding gene functions and identifying the biochemical state of an organism in response to genetic and environmental changes.
Assuntos
Biomarcadores , Metabolômica , Doenças da Boca , Saliva , Humanos , Saliva/metabolismo , Saliva/química , Biomarcadores/metabolismo , Doenças da Boca/metabolismo , PrognósticoRESUMO
In 2022, the 5th edition of the WHO classification of Head and Neck tumors was published online. In the salivary gland chapter, a new benign entity, the keratocystoma, was introduced. The sclerosing polycystic adenosis has been recognized as tumoral and is now termed sclerosing polycystic adenoma. The striated duct adenoma now has its own dedicated chapter. Additionally, a new variant of pleomorphic adenoma, termed "canalicular adenoma-like," has been incorporated. Regarding malignant tumors of the salivary glands, significant doubts now exist regarding the actual existence of oncocytic carcinoma, which has been reclassified among emerging entities. Two new malignant entities have also emerged: microsecretory adenocarcinoma and microcystic sclerosing adenocarcinoma. Finally, primary mucinous adenocarcinoma of the salivary glands has been acknowledged as a distinct entity.
Assuntos
Neoplasias das Glândulas Salivares , Organização Mundial da Saúde , Humanos , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/classificaçãoRESUMO
Polymorphous adenocarcinoma (PAC) is a common, usually low-grade salivary gland carcinoma. While conventional PACs are most associated with PRKD1 p.E710D hotspot mutations, the cribriform subtype is often associated with gene fusions in PRKD1, PRKD2, or PRKD3. These fusions have been primarily identified by fluorescence in situ hybridization (FISH) analysis, with a minority evaluated by next-generation sequencing (NGS). Many of the reported fusions were detected by break-apart FISH probes and therefore have unknown partners or were negative by FISH altogether. In this study, we aimed to further characterize the fusions associated with PAC with NGS. Fifty-four PACs (exclusively cribriform and mixed/intermediate types to enrich the study for fusion-positive cases) were identified and subjected to NGS. Fifty-one cases were successfully sequenced, 28 of which demonstrated gene fusions involving PRKD1, PRKD2, or PRKD3. There were 10 cases with the PRKD1 p.E710D mutation. We identified a diverse group of fusion partners, including 13 novel partners, 3 of which were recurrent. The most common partners for the PRKD genes were ARID1A and ARID1B. The wide variety of involved genes is unlike in other salivary gland malignancies and warrants a broader strategy of sequencing for molecular confirmation for particularly challenging cases, as our NGS study shows.
Assuntos
Adenocarcinoma , Neoplasias das Glândulas Salivares , Humanos , Hibridização in Situ Fluorescente , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Mutação , Fusão GênicaRESUMO
OBJECTIVES: In this systematic review, we aimed to evaluate the clinicopathological and prognosis data of patients with salivary gland myoepithelial carcinoma. MATERIALS AND METHODS: MEDLINE/PubMed, Scopus, and Embase search was performed with the keywords "myoepithelial carcinoma" "malignant myoepithelioma," and "salivary glands." Primary salivary glands myoepithelial carcinoma that fulfilled the World Health Organization diagnostic criteria were included. The Joanna Briggs Institute tool was used to assess the risk of bias. RESULTS: Forty-three studies (71 patients) met the inclusion criteria. The patients showed a mean age of 56.4 ± 19.6 years with no sex predilection. The parotid was the most affected gland (49.3%). The tumor presented as an asymptomatic (65.1%) mass (84%). The most common histological findings were the presence of clear tumor cells (39.7%) and multinodular growth patterns (60.7%). Multivariate analysis showed plasmacytoid cell type (p = 0.010) and solid growth pattern (p = 0.003) were related to decreased disease-free survival. Surgery alone was the most used treatment (53.5%). Patients with a combination of treatments showed a longer disease-free survival (p = 0.049). The 2-year and 5-year overall survival rates were 67.5% and 46.1%, respectively. CONCLUSION: Salivary gland myoepithelial carcinoma showed no sex predilection, with a higher incidence in the parotid gland. Cell type, growth pattern, and treatment type may be related to a lower disease-free survival. Overall, salivary gland myoepithelial carcinoma presented low recurrence and metastasis rates. Registration and protocol: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist and registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022311512).
Assuntos
Carcinoma , Mioepitelioma , Neoplasias das Glândulas Salivares , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Mioepitelioma/diagnóstico , Mioepitelioma/patologia , Mioepitelioma/secundário , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologia , Intervalo Livre de Doença , Carcinoma/patologiaRESUMO
OBJECTIVE: To describe the frequency, clinical, and demographic features of minor salivary gland tumors and possible associated factors. MATERIALS AND METHODS: A cross-sectional study was conducted. Clinical and demographic data were collected from biopsy records of two oral pathology services. Chi-square test, Fisher's exact test, and descriptive statistical analysis were performed. RESULTS: A total of 480 (0.89%) minor salivary gland tumors were retrieved, 272 (56.7%) benign and 147 (30.7%) malignant. Sixty-one (12.6%) had no subtype specification. Most patients were women (307/64.0%), in sixth decade of life (80/16.7%), with a mean age of 45.32 years. Palate was the most common site (336/70.1%). Pleomorphic adenoma (PA; 245/51.1%), mucoepidermoid carcinoma (MEC; 70/14.6%), and adenoid cystic carcinoma (ACC; 43/8.9%) were the most frequent tumors. Symptomatic case, recurrence, and tobacco use were associated with malignancy (p < 0.05). PA and MEC were more frequent in palate (p < 0.05). No association between the three most frequent histological types and gender or age group was observed (p > 0.05). CONCLUSIONS: This represents one of the largest exclusive series of minor salivary gland tumors in Brazil and worldwide. PA, MEC, and ACC were the most frequent tumors. Clinical and demographic data are similar from Brazilian studies or from other countries.
Assuntos
Adenoma Pleomorfo , Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Glândulas Salivares Menores , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/patologia , Adenoma Pleomorfo/epidemiologia , Adenoma Pleomorfo/patologia , Carcinoma Adenoide Cístico/epidemiologia , Carcinoma Adenoide Cístico/patologia , Demografia , Estudos RetrospectivosRESUMO
OBJECTIVES: The study aims to provide insights into the characteristics of Polish patients with different salivary gland pathologies. MATERIALS AND METHODS: This is a retrospective study conducted at a single center, including patients who underwent surgery for salivary gland pathologies between 2012 and 2022. RESULTS: This study included 239 patients who underwent surgery for salivary gland tumors or inflammatory diseases. Malignant tumors were diagnosed in 9.8% of participants, while 64% had benign tumors and 21% suffered from inflammation. The occurrence of complications after surgery was relatively low, with 9.9% of participants experiencing slight facial weakness or mild dysfunction, and 3% experiencing complete paralysis of the facial nerves. Significant differences were observed between patients with cancers and those with benign tumors and inflammation in terms of age. Cancers were more common in females (67% vs. 33%) and predominantly localized in the parotid glands (95%). CONCLUSION: Benign tumors, such as Warthin's tumors and polymorphous adenoma, were predominantly found in the parotid glands of patients aged 39-72 years. On the other hand, inflammatory diseases were primarily localized within the submandibular glands of males aged 40-68 years. Additionally, the presence of a malignant tumor was associated with longer hospitalization periods related to surgery and a higher risk of severe complications. CLINICAL RELEVANCE: This study on Polish patients with salivary gland tumors provides valuable clinical insights that can aid in diagnosis, treatment planning, patient counseling, and further research in the field of oncology. It contributes to the overall understanding of salivary gland tumors, potentially benefiting both patients and healthcare providers.
Assuntos
Adenolinfoma , Neoplasias das Glândulas Salivares , Feminino , Masculino , Humanos , Polônia/epidemiologia , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/cirurgia , InflamaçãoRESUMO
Salivary gland tumors (SGTs) comprise a rare and heterogenous category of benign/malignant neoplasms with progressively increasing knowledge of the molecular mechanisms underpinning their pathogenesis, poor prognosis, and therapeutic treatment efficacy. Emerging data are pointing toward an interplay of genetic and epigenetic factors contributing to their heterogeneity and diverse clinical phenotypes. Post-translational histone modifications such as histone acetylation/deacetylation have been shown to actively participate in the pathobiology of SGTs, further suggesting that histone deacetylating factors (HDACs), selective or pan-HDAC inhibitors (HDACis), might present effective treatment options for these neoplasms. Herein, we describe the molecular and epigenetic mechanisms underlying the pathology of the different types of SGTs, focusing on histone acetylation/deacetylation effects on gene expression as well as the progress of HDACis in SGT therapy and the current status of relevant clinical trials.
Assuntos
Neoplasias Encefálicas , Neoplasias das Glândulas Salivares , Humanos , Histonas/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Neoplasias das Glândulas Salivares/tratamento farmacológico , Neoplasias das Glândulas Salivares/genética , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , AcetilaçãoRESUMO
BACKGROUND: Salivary gland diseases are an important part of the work of ENT physicians in hospitals. The treatment strategies depend, among other things, on the doctrine at the respective location. OBJECTIVE: The aim of this questionnaire-based study was to assess the current diagnostic workup and therapeutic strategies for salivary gland diseases in German otorhinolaryngology departments. MATERIALS AND METHODS: A survey was performed using a 25-question online questionnaire sent to all German otorhinolaryngology department directors. RESULTS: The questionnaire was answered by 92 of 175 otorhinolaryngology departments (52.6%). In the diagnosis of salivary gland tumors, a dominance of sonography and MRI was shown. Fine- and core-needle aspiration were not performed by more than 50% of the clinics. The dominant technique for parotidectomy was under microscopic control (82%). In 99% of clinics, EMG was used during resection of the parotid gland for intraoperative monitoring of the facial nerve. There was a trend towards performing partial parotidectomies (85%), lateral parotidectomies (70%), and extracapsular dissections (57%) for benign tumors of the parotid gland. The treatment concepts for malignant tumors were inconsistent. CONCLUSION: In particular, the treatment strategy and extent of surgery for benign and malignant salivary gland tumors differed depending on location. The choice of palliative (drug) therapy was also diverse. Prospective multicenter studies could help to develop evidence-based treatment strategies.
Assuntos
Neoplasias Parotídeas , Doenças das Glândulas Salivares , Neoplasias das Glândulas Salivares , Humanos , Neoplasias Parotídeas/cirurgia , Estudos Prospectivos , Doenças das Glândulas Salivares/patologia , Glândula Parótida/patologia , Glândula Parótida/cirurgia , Hospitais , Inquéritos e Questionários , Estudos RetrospectivosRESUMO
Background: The aim of this study was to compare multiple objective ultrasound (US) texture features and develop an objective predictive model for predicting malignant major salivary glandular tumors. Methods: From August 2007 to May 2018, 144 adult patients who had major salivary gland tumors and subsequently underwent surgery were recruited for this study. Representative brightness mode US pictures were selected for texture analysis and used to develop a prediction model. Results: We found that the grayscale intensity and standard deviation of the intensity were significantly different between malignant and pleomorphic adenomas. The contrast, inverse difference (INV) movement, entropy, dissimilarity, and INV also differed significantly between benign and malignant tumors. We used stepwise selection of predictors to develop an objective predictive model, as follows: Score = 1.138 × Age - 1.814 × Intensity + 1.416 × Entropy + 1.714 × Contrast. With an optimal cutoff of 0.58, the diagnostic performance of this model had a sensitivity, specificity, overall accuracy, and area under the curve of 83% (95% confidence interval [CI]: 74%-92%), 74% (65%-84%), 78% (72%-85%), and 0.86 (0.80-0.92), respectively. Conclusion: We have developed a novel computerized diagnostic model based on objective US features to predict malignant major salivary gland tumor. Further improving the computer-aided diagnosis model might change the US examination for major salivary gland tumors in the future.
RESUMO
BACKGROUND: Larotrectinib is a first-in-class, highly selective, and central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. We report the efficacy and safety of larotrectinib in patients with TRK fusion-positive salivary gland cancers. PATIENTS AND METHODS: Patients with TRK fusion-positive salivary gland cancer treated with larotrectinib were identified from two clinical trials (NCT02122913 and NCT02576431). Patients received larotrectinib 100 mg twice daily (BID) except for one patient who received 150 mg BID in the phase I trial. The primary endpoint was objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: At the data cut-off (July 20, 2020), 24 patients with TRK fusion-positive salivary gland cancer had been treated. The most common histologies were secretory carcinoma (54%), adenocarcinoma (25%), and mucoepidermoid carcinoma (13%). All 24 patients had an ETV6-NTRK3 gene fusion. The ORR was 92% (95% confidence interval, 73-99). Best overall response was complete response in three (13%) patients, partial response in 19 (79%), and progressive disease in two (8%). The rate of progression-free survival at 24 months was 78% (median follow-up 30.9 months). Most treatment-related adverse events (AEs) were grade 1-2, and no patients discontinued treatment due to AEs. CONCLUSION: Larotrectinib demonstrated robust and durable efficacy in patients with TRK fusion-positive salivary gland tumors of various histologies, and a favorable safety profile. These findings support NTRK gene fusion testing in patients with advanced salivary gland cancers. CLINICALTRIALS.GOV NUMBERS: NCT02122913 and NCT02576431.
RESUMO
An early diagnosis of salivary gland tumors (SGTs) and determination of their malignancy are conducive to developing individualized therapeutic strategies and thus improving prognosis. The aim of this study was to investigate the difference of serum metabolic profiles in patients with SGTs to better understand the mechanism of this disease and disease risk stratification. We used ultrahigh-performance liquid chromatography Q Exactive mass spectrometry and multivariate statistical analyses to conduct a comprehensive analysis of serum metabolites in a population with normal control and SGTs. 32 differentially expressed metabolites were identified, while the level of serine and lactic acid were investigated to gradually upregulate in benign SGTs and malignant SGTs. Then, the expression of serine and lactic acid were assessed in validation cohort using multiple reaction monitoring (MRM) based targeted metabolite analysis. A risk score formula based on the amount of serine and lactic acid was developed and explored to be significantly related to benign SGTs and malignant SGTs in discovery and validation cohort. Our work highlights the possible use of the risk score assessment based on the serum metabolites not only reveal in the early diagnosis of SGTs but also assist in enhancing current therapeutic strategies in the clinic.
Assuntos
Neoplasias das Glândulas Salivares , Humanos , Ácido Láctico , Metabolômica , Prognóstico , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , SerinaRESUMO
BACKGROUND: Epithelial to mesenchymal transition promotes cell adhesion loss, enabling invasion and metastasis. MicroRNAs are a class of small non-codifying RNAs that regulate gene expression. OBJECTIVES: The aim of this study was to evaluate the expression of microRNAs that could regulate the expression of EMT factors in salivary gland tumors (SGTs). METHODS AND RESULTS: The expression of microRNAs miR-9, miR-34a, miR-101, miR-138, miR-155, and miR-200c-described in the literature to target EMT factors-was evaluated by Real-time RT-PCR (qPCR) in pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) samples. Bioinformatics tools were applied to identify miR targets and immunohistochemistry was used to examine the expression of the proteins E-cadherin, Twist, ZEB-1, ß-Catenin, and c-Kit. Comparing miR expression among SGT types, we observed increased expression of miR-9, and miR-138 in PAs, and increased miR-155 expression in MECs. Low-grade MECs exhibited increased miR-155 expression (p = 0.032). MECs that generated lymph node metastases had increased miR-200c levels (p = 0.018). MECs tended to have decreased expression of EMT-related proteins when compared to the other SGT types (c-Kit p < 0.001, Twist p = 0.014, and ZEB p = 0.012). Notably, increased c-Kit expression was associated with the presence of perineural infiltration in ACC (p = 0.050). CONCLUSIONS: This study provides evidence of alterations in the expression of EMT-factors regulating miRs, especially of miR-9, miR-138, miR-155, and miR-200c. No significant relationships were found between the expression of these miRs and proteins associated with EMT in SGTs.
Assuntos
MicroRNAs , Neoplasias das Glândulas Salivares , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias das Glândulas Salivares/genéticaRESUMO
Cancer stem cells are highly tumorigenic cells in the majority of the tumor that are responsible for the initiation, rapid growth, invasion, metastasis, and therapeutic resistance associated with various human cancers. The aim of this project is to assess a diagnostic and prognostic biomarker for the detection of cancer stem cells in salivary gland tumors using gold nanoparticles that are synthesized and conjugated to CD24 primer to form a CD24-Gold Nanocomposite. Sixty cases were included (29 pleomorphic adenoma, 19 carcinoma ex pleomorphic adenoma, and 12 normal controls). Alterations in biomarker expression between studied groups were analyzed and correlated with clinicopathological characteristics using Fisher's exact and Chi-square tests. ROC and Kaplan-Meier curves were used to validate diagnostic and prognostic values, respectively. This study confirms that CD24-Gold Nanocomposite served as a promising and highly sensitive biomarker in salivary gland tumor diagnosis and prognosis prediction.
Assuntos
Adenoma Pleomorfo , Nanopartículas Metálicas , Nanocompostos , Neoplasias das Glândulas Salivares , Humanos , Adenoma Pleomorfo/metabolismo , Adenoma Pleomorfo/patologia , Ouro/metabolismo , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Células-Tronco Neoplásicas/patologia , Prognóstico , Biomarcadores/metabolismo , Biomarcadores Tumorais/metabolismo , Antígeno CD24RESUMO
OBJECTIVES: To evaluate the clinical diagnostic value of contrast-enhanced ultrasound (CEUS) for focal benign and malignant lesions of the salivary glands, as well as for common benign lesions. METHODS: A total of 91 patients with focal lesions of the salivary glands were included in this study. In this study, CEUS was used to study the differential diagnosis of focal benign and malignant lesions of the salivary gland and the most common benign tumors, that is, pleomorphic adenoma (PA) and adenolymphoma. RESULTS: The differences between focal benign and malignant lesions in the salivary glands were statistically significant (P < .05) in terms of qualitative CEUS indicators, enhancement pattern, enhancement homogeneity, enhancement margin, and enhanced lesion size, whereas the differences were not statistically significant (P > .05) in terms of wash-in and wash-out pattern, enhancement degree. Blurred margins and increased size of the lesion after enhancement are two CEUS features independently associated with focal malignant lesions of the salivary gland. The differences between salivary gland PA and adenolymphoma were statistically significant (P < .05) in terms of wash-in pattern, enhancement degree, enhancement homogeneity, and enhancement pattern, but not in terms of wash-out pattern, enhancement margin, and enhanced lesion size (P > .05). CONCLUSIONS: As an economical, convenient, and safe imaging method, CEUS has important clinical value in distinguishing benign and malignant salivary glands.
Assuntos
Adenolinfoma , Adenoma Pleomorfo , Neoplasias das Glândulas Salivares , Meios de Contraste , Diagnóstico Diferencial , Humanos , Neoplasias das Glândulas Salivares/diagnóstico por imagem , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/diagnóstico por imagem , Glândulas Salivares/patologia , Sensibilidade e Especificidade , UltrassonografiaRESUMO
Currently, the diagnoses of oral diseases primarily depend on the visual recognition of experienced clinicians. It has been proven that automatic recognition based on images can support clinical decision-making by extracting and analyzing objective hidden information. In recent years, optical coherence tomography (OCT) has become a powerful optical imaging technique with the advantages of high resolution and non-invasion. In our study, a dataset composed of four kinds of oral salivary gland tumors (SGTs) was obtained from a homemade swept-source OCT, including two benign and two malignant tumors. Seventy-six texture features were extracted from OCT images to create computational models of diseases. It was demonstrated that the artificial neural network (ANN) based on principal component analysis (PCA) can obtain high diagnostic sensitivity and specificity (higher than 99%) for these four kinds of tumors. The classification accuracy of each tumor is larger than 99%. In addition, the performances of two classifiers (ANN and support vector machine) were quantitatively evaluated based on SGTs. It was proven that the texture features in OCT images provided objective information to classify oral tumors.