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Oral Oncology Dec 2021Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland malignancies. Our aim was to evaluate the prognostic impact of primary tumor site in patients...
UNLABELLED
Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland malignancies. Our aim was to evaluate the prognostic impact of primary tumor site in patients with MEC.
MATERIAL AND METHODS
This cohort identified 308 patients with MEC who underwent primary surgery between 1985 and 2015. Survival outcomes were determined using the Kaplan-Meier method. Hazard ratios for primary site were determined using the Cox proportional-hazards model.
RESULTS
One hundred eighty (58%) patients were diagnosed with minor and 128 (42%) with major salivary gland cancer. Primary site in the minor salivary gland group included 137 (44%) oral cavity, 38 (12%) pharynx, 3 (0.9%) nasal cavity, and 2 (0.6%) trachea and larynx. The major salivary gland group included 118 (38%) parotid, 8 (3%) submandibular, and 2 (0.6%) sublingual. With a median follow-up of 73 months, 5-year overall survival and disease-specific survival were 84% and 91%, respectively. Patients with tumors located in the hard palate and retromolar trigone had the best survival, while patients with tumors located in the paranasal sinuses and submandibular gland had the poorest survival. After controlling for tumor grade and stage, MEC primary site was not predictive of survival or recurrence. On multivariate analysis, worse DSS was associated with stage III-IV tumors (HR: 7,11; 95% CI: 1.19-26.43; p = 0.0034) and high-grade tumors (HR: 19.12; 95% CI: 2.26-162.77; p = 0.0068).
CONCLUSIONS
While high grade and advanced overall stage were found to be independent predictors of worse survival, primary tumor site was not predictive of poor outcome.
Topics: Carcinoma, Mucoepidermoid; Humans; Neoplasm Staging; Prognosis; Retrospective Studies; Salivary Gland Neoplasms; Survival Rate
PubMed: 34768210
DOI: 10.1016/j.oraloncology.2021.105602 -
Head and Neck Pathology Mar 2013Mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy of the upper aerodigestive tract and tracheobronchial tree, is also known for its considerable... (Review)
Review
Mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy of the upper aerodigestive tract and tracheobronchial tree, is also known for its considerable cellular heterogeneity including epidermoid, intermediate and mucin producing cells. Despite this structural and cellular heterogeneity, MEC is uniquely characterized by a specific translocation t(11; 19) (q12; p13), resulting in a fusion between the MECT1 and the MAML2 genes. Although the incidence of this fusion in MEC varies, it is generally accepted that more than 50 % of this entity manifest the MECT1-MAML2. Fusion-positive cases showed significantly better survival than fusion-negative cases, suggesting that MECT1-MAML2 represents a specific prognostic molecular marker in MEC. We contend that fusion in MEC represents a distinct mechanism in the development of this entity. In that context, fusion positive MEC, regardless of grade, manifest a more stable genome and better clinical behaviour, while fusion negative MEC represent a distinctly different pathway characterized by marked genomic instability and relatively aggressive tumors.
Topics: Carcinoma, Mucoepidermoid; Humans; Oncogene Proteins, Fusion; Salivary Gland Neoplasms
PubMed: 23459841
DOI: 10.1007/s12105-013-0432-5 -
Acta Otorrinolaringologica Espanola 2016
Topics: Carcinoma, Mucoepidermoid; Child; Humans; Male; Parotid Neoplasms
PubMed: 26976338
DOI: 10.1016/j.otorri.2015.11.005 -
Virchows Archiv : An International... Nov 2021Mucoepidermoid carcinoma (MEC) is the most common carcinoma of the salivary glands. Here, we have used two large patient cohorts with MECs comprising 551 tumors to study... (Comparative Study)
Comparative Study
Mucoepidermoid carcinoma (MEC) is the most common carcinoma of the salivary glands. Here, we have used two large patient cohorts with MECs comprising 551 tumors to study clinical, histological, and molecular predictors of survival. One cohort (n = 167), with known CRCT1/3-MAML2 fusion status, was derived from the Hamburg Reference Centre (HRC; graded with the AFIP and Brandwein systems) and the other (n = 384) was derived from the population-based Cancer Registry of North Rhine-Westphalia (LKR-NRW; graded with the AFIP system). The reliability of both the AFIP and Brandwein grading systems was excellent (n = 155). The weighted kappa for inter-rater agreement was 0.81 (95% CI 0.65-0.97) and 0.83 (95% CI 0.71-0.96) for the AFIP and Brandwein systems, respectively. The 5-year relative survival was 79.7% (95% CI 73.2-86.2%). Although the Brandwein system resulted in a higher rate of G3-MECs, survival in G3-tumors (AFIP or Brandwein grading) was markedly worse than in G1/G2-tumors. Survival in > T2 tumors was markedly worse than in those with lower T-stage. Also, fusion-negative MECs had a worse 5-year progression-free survival. The frequency of fusion-positive MECs in the HRC cohort was 78.4%, of which the majority (86.7%) was G1/G2-tumors. In conclusion, the AFIP and Brandwein systems are useful in estimating prognosis and to guide therapy for G3-MECs. However, their significance regarding young age (≤ 30 years) and location-dependent heterogeneity of in particular G2-tumors is more questionable. We conclude that CRTC1/3-MAML2 testing is a useful adjunct to histologic scoring of MECs and for pinpointing tumors with poor prognosis with higher precision, thus avoiding overtreatment.
Topics: Adolescent; Adult; Biomarkers, Tumor; Carcinoma, Mucoepidermoid; Female; Gene Fusion; Germany; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Predictive Value of Tests; Progression-Free Survival; Registries; Salivary Gland Neoplasms; Time Factors; Trans-Activators; Transcription Factors; Young Adult
PubMed: 34231055
DOI: 10.1007/s00428-021-03146-x -
Journal of Cancer Research and... 2015Central mucoepidermoid carcinomas (MECs) are extremely rare tumors, comprising 2-3% of all MECs reported in the literature. We report a rare case of clear cell variant...
Central mucoepidermoid carcinomas (MECs) are extremely rare tumors, comprising 2-3% of all MECs reported in the literature. We report a rare case of clear cell variant of central MEC with calcifications occurring in the left posterior mandible in a 37-year-old male patient.
Topics: Adult; Carcinoma, Mucoepidermoid; Diagnosis, Differential; Humans; Male; Mandibular Neoplasms; Radiography
PubMed: 26458654
DOI: 10.4103/0973-1482.138038 -
Cells Jan 2020Mucoepidermoid carcinoma (MEC) is the most common tumor in the salivary glands, often presenting with recurrence and metastasis due to its high invasive capacity....
Mucoepidermoid carcinoma (MEC) is the most common tumor in the salivary glands, often presenting with recurrence and metastasis due to its high invasive capacity. Metallothionein (MT), a zinc storage protein that supplies this element for protease activity, is probably related to mucoepidermoid carcinoma behavior. This prompted us to characterize a cell line derived from mucoepidermoid carcinoma and to correlate metallothionein expression with transforming growth factor-α (TGF-α), tumor necrosis factor-α (TNF-α) and matrix metalloproteinases (MMPs). Transcriptomic analysis and cytogenetic assays were performed to detect the expression of genes of interest and cellular chromosomal alterations, respectively. MEC cells with a depleted metallothionein 2A () gene were subjected to Western blot to correlate metallothionein expression with growth factors and MMPs. Additionally, cells with depleted MT were subjected to migration and invasion assays. The transcriptomic study revealed reads mapped to cytokeratins 19 and AE1/AE3, α-smooth muscle actin, vimentin, and fibronectin. Cytogenetic evaluation demonstrated structural and numerical alterations, including the translocation t(11;19)(q21;p13), characteristic of MEC. Metallothionein depletion was correlated with the decreased expression of TGF-α and MMP-9, while TNF-α protein levels were augmented. Migration and invasion activity were diminished after metallothionein silencing. Our findings suggest an important role of MT in MEC invasion, through the regulation of proteins involved in this process.
Topics: Biomarkers, Tumor; Carcinoma, Mucoepidermoid; Epithelial-Mesenchymal Transition; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; In Vitro Techniques; Matrix Metalloproteinases; Metallothionein; Tumor Cells, Cultured
PubMed: 31936364
DOI: 10.3390/cells9010157 -
Cancer Medicine May 2023Mucoepidermoid carcinoma (MEC) of the breast is an extremely rare salivary gland-type tumor characterized by epidermoid, basaloid, intermediate, and/or mucinous cells...
Mucoepidermoid carcinoma (MEC) of the breast is an extremely rare salivary gland-type tumor characterized by epidermoid, basaloid, intermediate, and/or mucinous cells arranged in solid and cystic patterns. Despite their triple-negative phenotype, breast MECs are generally considered low-risk malignancies but their biology is largely unexplored; therefore, guidelines for clinical management are lacking. Here, we sought to characterize the molecular landscape of breast MECs. Thirteen cases were histologically reviewed, characterized for tumor-infiltrating lymphocytes (TILs), and were subjected to immunohistochemistry for programmed death-ligand 1 (PD-L1, clone 22C3), EGFR, and amphiregulin (AREG). Rearrangements in MAML2 and EWSR1 were investigated by fluorescent in situ hybridization. Targeted next-generation sequencing of 161 genes was performed on eight cases. Most MECs had low histological grade (n = 10, 77%), with the presence of TILs (n = 9/12; 75%) and PD-L1 combined positive score ranging from 10 to 20 (n = 4/6; 67%). All cases showed EGFR and AREG overexpression and were fusion negative. Enrichment of genetic alterations was observed in PI3K/AKT/mTOR and cell cycle regulation pathways, while only one case harbored TP53 mutations. This is the first study providing extensive molecular data on breast MECs and the largest collection of cases available to date in the literature. Breast MECs lack TP53 mutations found in high-grade forms of triple-negative breast cancers and MAML2 or EWSR1 rearrangements pathognomonic of salivary MECs. Triple-negativity and PD-L1 positivity suggest a window of opportunity for immunotherapy in these patients. The EGFR/AREG axis activation, coupled with the mutational patterns in PI3K/AKT/mTOR and cell cycle pathways warrants caution in considering MECs as low-risk neoplasms.
Topics: Humans; DNA-Binding Proteins; Trans-Activators; B7-H1 Antigen; In Situ Hybridization, Fluorescence; Carcinoma, Mucoepidermoid; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Nuclear Proteins; Transcription Factors; Salivary Gland Neoplasms; ErbB Receptors; TOR Serine-Threonine Kinases; Biomarkers, Tumor
PubMed: 36916425
DOI: 10.1002/cam4.5754 -
Head and Neck Pathology Dec 2022Salivary gland mucoepidermoid carcinoma (MEC) poses a considerable risk of locoregional and distant metastasis after conventional treatments. There is an evident need...
BACKGROUND
Salivary gland mucoepidermoid carcinoma (MEC) poses a considerable risk of locoregional and distant metastasis after conventional treatments. There is an evident need for specifying prognostic biomarkers to identify patients who are in need of more intensive and prolonged follow-ups. This study aimed to assess the mucin 1 (MUC1) expression level and its potential regulatory microRNAs in salivary gland MEC and their prognostic potentials.
MATERIALS AND METHODS
The expression of MUC1 in salivary gland MEC tissues was assessed in 47 samples using immunohistochemistry. Related microRNA (miR-145 and miR-21) were evaluated using quantitative Reverse Transcription PCR. The associations between MUC1 and microRNAs expressions and clinicopathological parameters were investigated.
RESULTS
MUC1 expression levels positively correlated with histologic grade (p < 0.001), clinical stage (p = 0.04), risk of nodal metastasis (p = 0.02), as well as the likelihood of opting for radical treatment (p = 0.01). Increased expression of miR-21 (p < 0.001) and decreased expression of miR-145 (p < 0.001) were observed in MECs compared to normal salivary gland tissue. MiR-145 negatively (p = 0.01) and miR-21 positively (p = 0.01) correlated with MUC1 overexpression. Based on the univariate cox proportional hazard model, histologic grade and MUC1 expression level were significantly associated with disease-free, cancer-specific, and overall survival. However, the multivariable cox proportional hazard model indicated tumor grade as the only prognostic factor associated with disease-free survival.
CONCLUSION
Our results support the tumor suppressor role of miR-145 and the oncogenic role of miR-21 in salivary gland MEC. Also, MUC1 and miR-145 overexpression, as well as miR-21 suppression, show promising association with histologic tumor grade and clinical stage.
Topics: Humans; Carcinoma, Mucoepidermoid; Mucin-1; Prognosis; MicroRNAs
PubMed: 35980523
DOI: 10.1007/s12105-022-01475-0 -
Science Progress 2023Warthin tumor (WT)-like mucoepidermoid carcinoma resembles the histologic pattern of WT and pathologists unaware of this possibility may misdiagnose it as WT with... (Review)
Review
Warthin tumor (WT)-like mucoepidermoid carcinoma resembles the histologic pattern of WT and pathologists unaware of this possibility may misdiagnose it as WT with squamous and mucous epithelium metaplasia or WT malignant transfer into mucoepidermoid carcinoma. The present study reported a case of a 41-year-old Chinese female with a solitary mass in the left parotid gland. In this case, microscopic observation revealed prominent lymph node stroma and multiple cystic structures similar to those seen in WT. However, it lacked the two layers of oncocytic epithelial tissue characteristic of WT. Furthermore, fluorescence hybridization detected MAML2 rearrangement in the case. Considering the histological findings, this case was diagnosed as WT-like mucoepidermoid carcinoma. The present case report provides pathological and clinical features to differentiate it from WT malignant transition into mucoepidermoid carcinoma, WT with squamous and mucous epithelium metaplasia and non-sebaceous lymphadenoma-like mucoepidermoid carcinoma. In conclusion, WT-like mucoepidermoid carcinoma as a special subtype of mucoepidermoid carcinoma has special histological characteristics, which required further observations and more case reports to clearly define this variant.
Topics: Female; Humans; Adult; Parotid Gland; Carcinoma, Mucoepidermoid; In Situ Hybridization, Fluorescence; Adenolymphoma; Metaplasia; Carcinoma, Squamous Cell
PubMed: 37335119
DOI: 10.1177/00368504231179816 -
Esophagus : Official Journal of the... Oct 2020Submucosal glands (SMGs) present throughout human esophagus with clusters at either the upper third or lower third of the organ. SMGs tend to atrophy with age, and... (Review)
Review
Submucosal glands (SMGs) present throughout human esophagus with clusters at either the upper third or lower third of the organ. SMGs tend to atrophy with age, and neoplasms arising in these glands are rare. In order to bring convenience to diagnosis, we summarize the histopathologic characteristics of all esophageal submucosal gland tumors (SGTs). Due to the morphological similarity, the nomenclature of salivary tumors is adopted for SGTs. However, there is great confusion about the definition and histogenesis of these tumors, especially the malignant subtypes. In the literature, esophageal mucoepidermoid carcinoma and adenoid cystic carcinoma usually adjoin the surface squamous epithelium and coexist with intraepithelial neoplasia or invasive squamous cell carcinoma (SCC). In addition, the typical gene alterations of salivary tumors have not been reported in these SGTs. Therefore, we propose to apply stringent diagnostic criteria to esophageal SGTs so as to exclude mimickers that are SCCs with various degree of SMG differentiation.
Topics: Aged, 80 and over; Atrophy; Carcinoma in Situ; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagus; Humans; Keratins; Male; Mucin-5B; Neoplasms, Glandular and Epithelial; Retrospective Studies
PubMed: 32621256
DOI: 10.1007/s10388-020-00758-1