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Journal of Oral Pathology & Medicine :... Jul 2022To evaluate the potential use of Cephaeline as a therapeutic strategy to manage mucoepidermoid carcinomas (MEC) of the salivary glands.
AIM
To evaluate the potential use of Cephaeline as a therapeutic strategy to manage mucoepidermoid carcinomas (MEC) of the salivary glands.
MATERIAL AND METHODS
UM-HMC-1, UM-HMC-2, and UM-HMC-3A MEC cell lines were used to establish the effects of Cephaeline over tumor viability determined by MTT assay. In vitro wound healing scratch assays were performed to address cellular migration while immunofluorescence staining for histone H3 lysine 9 (H3k9ac) was used to identify the acetylation status of tumor cells upon Cephaeline administration. The presence of cancer stem cells was evaluated by the identification of ALDH enzymatic activity by flow cytometry and through functional assays using in vitro tumorsphere formation.
RESULTS
A single administration of Cephaeline resulted in reduced viability of MEC cells along with the halt on tumor growth and cellular migration potential. Administration of Cephaeline resulted in chromatin histone acetylation as judged by the increased levels of H3K9ac and disruption of tumorspheres formation. Interestingly, ALDH levels were increased in UM-HMC-1 and UM-HMC-3A cell lines, while UM-HMC-2 showed a reduced enzymatic activity.
CONCLUSION
Cephaeline has shown anti-cancer properties in all MEC cell lines tested by regulating tumor cells' viability, migration, proliferation, and disrupting the ability of cancer cells to generate tumorspheres.
Topics: Acetylation; Carcinoma, Mucoepidermoid; Cell Line, Tumor; Emetine; Histones; Humans; Neoplastic Stem Cells
PubMed: 34661317
DOI: 10.1111/jop.13252 -
Annals of Medicine 2023To improve diagnostic accuracy of pulmonary mucoepidermoid carcinoma (PMEC) through multi-detector computed tomography (MSCT) findings.
OBJECTIVES
To improve diagnostic accuracy of pulmonary mucoepidermoid carcinoma (PMEC) through multi-detector computed tomography (MSCT) findings.
METHODS
MSCT findings of 27 histopathologically confirmed PMEC cases were retrospectively analyzed, including the location, size, margin, density, enhancement of the lesion and accompanying signs.
RESULTS
Among the 27 PMEC cases, 6 (6/27, 22.2%) were the large airway pattern, 14 were (14/27, 51.9%) the pulmonary hilum pattern, and 7 (7/27, 26.9%) were the peripheral pattern. Among those 20 cases with central pattern(6 large airway and 14 pulmonary hilum patterns), 6 presented mild enhancement, 4 moderate enhancement, 5 severe enhancement, 5 heterogeneous enhancement, and 3 with calcification. 7 cases with peripheral patterns were presented as solid pulmonary nodules and masses, 3 with severe enhancement, 1 with moderate enhancement and 3 with mild enhancement. Four cases accompanied by lymph nodal metastasis, and 7 cases with distant organ metastasis. Age( = -3.132, = 0.005), enlarged lymph node ( = 9.281, = 0.005), and distant metastasis( = 7.816, = 0.008) were statistically significant in the low-grade group and high-grade group.
CONCLUSIONS
MSCT images of PMEC patients demonstrated some characteristic findings, which would help improve the diagnostic accuracy of the disease.
Topics: Humans; Child, Preschool; Carcinoma, Mucoepidermoid; Retrospective Studies; Lung Neoplasms
PubMed: 37783202
DOI: 10.1080/07853890.2023.2263869 -
Modern Pathology : An Official Journal... Mar 2017Sclerosing mucoepidermoid carcinoma with eosinophilia is a rare thyroid neoplasm of uncertain pathogenesis that resembles salivary gland mucoepidermoid carcinoma. This...
Sclerosing mucoepidermoid carcinoma with eosinophilia is a rare thyroid neoplasm of uncertain pathogenesis that resembles salivary gland mucoepidermoid carcinoma. This multi-institutional study characterizes the clinicopathologic and molecular features of this tumor by utilizing next-generation sequencing to assess common mutations and gene fusions involved in thyroid carcinogenesis as well as fluorescence in-situ hybridization for MAML2 translocations typical of salivary gland mucoepidermoid carcinoma. Nine cases (6 females and 3 males, mean age: 59 years, range 30-77 years) were identified. All cases were comprised of nests and strands of tumor cells with both squamous and mucinous differentiation embedded in a fibrohyaline stroma with an inflammatory infiltrate replete with eosinophils. All cases were p63 positive, thyroglobulin negative and showed variable expression of TTF-1. All nine cases were negative for MAML2 rearrangements. Five cases successfully tested by next-generation sequencing (ThyroSeq v.2 assay) were negative for mutations and translocations commonly involved in thyroid carcinogenesis. NTRK1 showed overexpression but no evidence of translocation. On follow-up, one patient died of persistent disease, whereas one of four remaining patients with available follow-up (mean: 7.3 years, range 4-11 years) demonstrated recurrence at 4 years. Thus, we show that sclerosing mucoepidermoid carcinoma with eosinophilia appears molecularly and morphologically distinct from follicular and C-cell-derived thyroid tumors as well as from salivary gland mucoepidermoid carcinoma. The overall and recurrence-free survival for these patients may be lower than for other well-differentiated thyroid cancers.
Topics: Adult; Aged; Carcinoma, Mucoepidermoid; Disease-Free Survival; Eosinophilia; Female; Gene Fusion; Humans; Male; Middle Aged; Mutation; Prognosis; Thyroid Gland; Thyroid Neoplasms; Translocation, Genetic
PubMed: 27910944
DOI: 10.1038/modpathol.2016.180 -
Indian Journal of Dental Research :... 2018Cancer stem cells (CSCs) may participate in angiogenesis by lining the wall of tumor vessels.
BACKGROUND
Cancer stem cells (CSCs) may participate in angiogenesis by lining the wall of tumor vessels.
AIM
The current study aimed to present the role of vimentin and CD44 in inducing vasculogenic mimicry (VM) and epithelial-mesenchymal transition (EMT) in different grades of mucoepidermoid carcinoma (MEC).
MATERIALS AND METHODS
A total of 63 MEC samples were collected from the archive of Department of Pathology of Taleghani Educational Hospital, Tehran, Iran. Vimentin and CD44/periodic acid-Schiff double staining was performed.
STATISTICAL ANALYSIS
Chi-square test was used to examine the differences with categorical variables. Significance level was set at 0.05. Pearson's correlation coefficient was used to assess the colocalization of the markers.
RESULTS
There were statistically significant differences between tumor grade and the expression levels of vimentin and CD44 (P = 0.000).
CONCLUSION
Our results may disclose a definite relationship between microvessl density (MVD), VM, EMT, and CSCs in MEC samples. Thus, it is reasonable to suggest that CSCs are related to angiogenesis and VM.
Topics: Adult; Biomarkers, Tumor; Carcinoma, Mucoepidermoid; Female; Humans; Hyaluronan Receptors; Immunohistochemistry; Male; Middle Aged; Mouth Neoplasms; Neovascularization, Pathologic; Vimentin
PubMed: 29900918
DOI: 10.4103/ijdr.IJDR_184_17 -
Journal of Medical Case Reports Dec 2023Mucoepidermoid carcinoma of the breast is a rare special type of salivary gland-like tumor of the breast, usually displaying triple-negative phenotype. To date, only 64... (Review)
Review
BACKGROUND
Mucoepidermoid carcinoma of the breast is a rare special type of salivary gland-like tumor of the breast, usually displaying triple-negative phenotype. To date, only 64 cases have been reported in the English literature. Herein, we report the first case of mucoepidermoid carcinoma of the breast with human epidermal growth factor receptor 2 gene amplification.
CASE PRESENTATION
A 58-year-old Caucasian woman treated with breast-conserving surgery, radiotherapy, and chemotherapy for an invasive breast carcinoma of no special type, relapsed 20 years later in the ipsilateral left breast. Histological examination of the core needle biopsy of the relapse deferred to the surgical specimen for the definitive diagnosis, because of the broad differential diagnosis. On the resected specimen we observed the presence of a poorly differentiated carcinoma with mucoepidermoid carcinoma of the breast typical features consisting of epidermoid, intermediate and mucinous cells lacking true keratinization, in keeping with the latest World Health Organization diagnostic criteria. The mucoepidermoid carcinoma of the breast was weakly estrogen receptor and androgen receptor positive and progesterone receptor negative, but exceptionally showed human epidermal growth factor receptor 2 gene amplification. Mastermind-like transcriptional coactivator 2 gene translocations were not detected by fluorescent in situ hybridization. The patient received adjuvant chemotherapy with anti-human epidermal growth factor receptor 2 therapy but no endocrine therapy. After 61 months of follow-up, no signs of local or distant recurrence were observed.
CONCLUSIONS
Mucoepidermoid carcinoma of the breast is a very rare entity. Despite being most frequently triple negative, the standard evaluation of receptor status is mandatory, as well as strict application of World Health Organization diagnostic criteria for correct patient management.
Topics: Female; Humans; Middle Aged; Carcinoma, Mucoepidermoid; In Situ Hybridization, Fluorescence; Neoplasm Recurrence, Local; Breast Neoplasms; Salivary Glands
PubMed: 38062474
DOI: 10.1186/s13256-023-04233-0 -
Viruses Oct 2022Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor gene fusions, but the...
Mucoepidermoid Carcinomas (MEC) represent the most common malignancies of salivary glands. Approximately 50% of all MEC cases are known to harbor gene fusions, but the additional molecular drivers remain largely uncharacterized. Here, we sought to resolve controversy around the role of human papillomavirus (HPV) as a potential driver of mucoepidermoid carcinoma. Bioinformatics analysis was performed on 48 MEC transcriptomes. Subsequent targeted capture DNA sequencing was used to annotate HPV content and integration status in the host genome. HPV of any type was only identified in 1/48 (2%) of the MEC transcriptomes analyzed. Importantly, the one HPV16+ tumor expressed high levels of p16, had high expression of HPV16 oncogenes E6 and E7, and displayed a complex integration pattern that included breakpoints into 13 host genes including , , , and as well as 9 non-genic regions. In this cohort, HPV is a rare driver of MEC but may have a substantial etiologic role in cases that harbor the virus. Genetic mechanisms of host genome integration are similar to those observed in other head and neck cancers.
Topics: Humans; Carcinoma, Mucoepidermoid; DNA-Binding Proteins; Alphapapillomavirus; Papillomaviridae; Papillomavirus Infections; Trans-Activators; Nuclear Proteins; Transcription Factors
PubMed: 36366450
DOI: 10.3390/v14112353 -
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 -
PloS One 2014Primary pulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has...
INTRODUCTION
Primary pulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19) resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied.
METHODS
We detected MAML2 rearrangement using fluorescence in situ hybridization (FISH) in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC), and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC). The findings were then examined regarding the clinicopathological parameters and patient outcomes.
RESULTS
FISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; p = 0.001) and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p<0.001 and p = 0.023, respectively). Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (p = 0.023) or disease-free survival (p = 0.027) as well as correlation between FLT1 and overall survival (p = 0.009).
CONCLUSIONS
MAML2 rearrangement appears frequent in PMEC and specific with this tumor. Both the presence of MAML2 rearrangement and absence of FLT1 tend to confer a favorable clinical outcome. These findings suggest that molecular detection of MAML2 rearrangement combined with FLT1 may be of important clinical value for PMEC.
Topics: Adolescent; Adult; Aged; Carcinoma, Mucoepidermoid; DNA-Binding Proteins; Female; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Nuclear Proteins; Oncogene Proteins, Fusion; Prognosis; Salivary Gland Neoplasms; Trans-Activators; Transcription Factors; Translocation, Genetic; Vascular Endothelial Growth Factor Receptor-1; Young Adult
PubMed: 24714697
DOI: 10.1371/journal.pone.0094399 -
Korean Journal of Radiology 2015The maximum standardized uptake value (SUVmax) of pulmonary mucoepidermoid carcinoma (PMEC) in fluorine-18fluorodeoxyglucose positron emission tomography/computed...
OBJECTIVE
The maximum standardized uptake value (SUVmax) of pulmonary mucoepidermoid carcinoma (PMEC) in fluorine-18fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) was evaluated as a preoperative predictor of pathologic grade and survival rate.
MATERIALS AND METHODS
Twenty-three patients who underwent preoperative PET/CT and complete resection for PMEC were enrolled. The optimal cut-off SUVmax for tumor grade was calculated as 6.5 by receiver operating characteristic curve. The patients were divided into a high SUV group (n = 7) and a low SUV group (n = 16). Clinicopathologic features were compared between the groups by χ(2) test and overall survival was determined by Kaplan-Meier analysis.
RESULTS
The mean SUVmax was 15.4 ± 11.5 in the high SUV group and 3.9 ± 1.3 in the low SUV group. All patients except one from the low SUV group had low grade tumors and all had no nodal metastasis. The sensitivity and specificity of SUVmax from PET/CT for predicting tumor grade was 85.7% and 93.8%, respectively. During the follow-up period (mean, 48.6 ± 38.7 months), four patients from the high SUV group experienced cancer recurrence, and one died of cancer. In contrast, none of the low SUV group had recurrence or mortality. Five-year overall survival rate was significantly higher in the low SUV group (100% vs. 71.4%, p = 0.031).
CONCLUSION
Pulmonary mucoepidermoid carcinoma patients with high SUVmax in PET/CT had higher tumor grade, more frequent lymph node metastasis and worse long-term outcome. Therefore, PMEC patients with high uptake on PET/CT imaging might require aggressive mediastinal lymph node dissection and adjuvant therapies.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Mucoepidermoid; Female; Fluorodeoxyglucose F18; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Mediastinum; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Positron-Emission Tomography; Prognosis; ROC Curve; Retrospective Studies; Sensitivity and Specificity; Survival Rate; Tomography, X-Ray Computed; Young Adult
PubMed: 26175595
DOI: 10.3348/kjr.2015.16.4.929 -
Diagnostic Pathology Jan 2024Mammary mucoepidermoid carcinoma (MEC) is a rare entity. The molecular characteristics of breast MEC have not been fully investigated due to its rarity. We performed a...
Mammary mucoepidermoid carcinoma (MEC) is a rare entity. The molecular characteristics of breast MEC have not been fully investigated due to its rarity. We performed a retrospective study among 1000 patients with breast carcinomas and identified four cases of breast MEC. Clinical and demographic data were collected. Immunohistochemistry panels which were used to diagnose salivary gland MEC and breast carcinomas were also performed. MAML2 rearrangements were detected by FISH and fusion partners were identified by RNA sequencing. Whole-exome sequencing (WES) was used to reveal the genomes of these four breast MEC. Then, the biological functions and features of breast MEC were further compared with those of invasive breast carcinomas and salivary gland MEC.According to Ellis and Auclair's methods, these four breast MEC could be classified as low-grade breast MEC. All the patients were alive, and disease-free survival (PFS) ranged from 20 months to 67 months. Among these four breast MEC, two cases were triple-negative, and the other two cases were found to be ER positive, with one also showing HER2 equivocal by immunohistochemical staining, but no amplification in FISH. FISH analysis confirmed the presence of the MAML2 translocation in three of four tumors, and CRTC1-MAML2 fusion was confirmed in two of them by RNA-sequencing. The average coverage size of WES for the tumor mutation burden estimation was 32 Mb. MUC4, RP1L1 and QRICH2 mutations were identified in at least three tumors, and these mutation also existed in breast invasive carcinoma databases (TCGA, Cell 2015; TCGA, Nature 2012). The results showed that there were many genes in breast MEC overlapping with the breast invasive carcinoma databases mentioned above, range from 5 to 63 genes (median:21 genes). Next, we assessed immune cell infiltration levels in these tumors. In all these tumors, M2 macrophages and plasma cell were in the high infiltration group. Our breast MEC showed different results from the salivary gland MEC, whose plasma cells were in the low infiltration group. Overall, we first analyzed the genomics and tumor microenvironment of breast mucoepidermoid carcinoma and proposed our hypothesis that although MECs arising in the breast resemble their salivary gland counterparts phenotypically, our findings indicate that breast MECs probably resemble invasive breast carcinomas at the genetic level and immune cell infiltration levels. More cases and in deep research need to be done to further understand this rare carcinoma.
Topics: Humans; Female; DNA-Binding Proteins; Trans-Activators; Retrospective Studies; Carcinoma, Mucoepidermoid; Exome; Exome Sequencing; Tumor Microenvironment; Transcription Factors; Breast Neoplasms; Salivary Gland Neoplasms; Genomics; Sequence Analysis, RNA; Eye Proteins
PubMed: 38243319
DOI: 10.1186/s13000-024-01439-8