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Vaccines Sep 2022Salivary gland neoplasms are a heterogeneous neoplasm group, including mucoepidermoid carcinoma (MECa), adenoid cystic carcinoma (AdCC), and many others.
UNLABELLED
Salivary gland neoplasms are a heterogeneous neoplasm group, including mucoepidermoid carcinoma (MECa), adenoid cystic carcinoma (AdCC), and many others.
OBJECTIVE
We aimed to identify new critical genes of MECa and AdCC using bioinformatics analysis.
METHODS
Gene expression profile of GSE153283 was analyzed by the GEO2R online tool to use the DAVID software for their subsequent enrichment. Protein-protein interactions (PPI) were visualized using String. Cytoscape with MCODE plugin followed by Kaplan-Meier online for overall survival analysis were performed.
RESULTS
97 upregulated genes were identified for MECa and 86 for AdCC. PPI analysis revealed 22 genes for MECa and 63 for AdCC that were validated by Kaplan-Meier that showed FN1 and SPP1 for MECa, and EGF and ERBB2 for AdCC as more significant candidate genes for each neoplasm.
CONCLUSION
With bioinformatics methods, we identify upregulated genes in MECa and AdCC. The resulting candidate genes as possible therapeutic targets were FN1, SPP1, EGF, and ERBB2, and all those genes had been tested as a target in other neoplasm kinds but not salivary gland neoplasm. The bioinformatic evidence is a solid strategy to select them for more extensive research with clinical impact.
PubMed: 36146635
DOI: 10.3390/vaccines10091557 -
Cancer Cytopathology Oct 2022Mucoepidermoid carcinoma (MEC) is the most common salivary gland (SG) malignancy. In this study, the author undertook analysis of a large collection of MEC cytologic...
BACKGROUND
Mucoepidermoid carcinoma (MEC) is the most common salivary gland (SG) malignancy. In this study, the author undertook analysis of a large collection of MEC cytologic cases.
MATERIALS AND METHODS
Cytopathology files were searched for MEC cases with histopathologic confirmation. Fine-needle aspiration (FNA) smears used standard technique.
RESULTS
Seventy-six cases (63 patients [M:F = 1:1; age range, 23-87 years; mean age, 58 years]) met inclusion criteria. Aspirates were primary (54 [71%]), metastatic (18 [24%]), and locally recurrent (4 [5%]). FNA sites included parotid gland (49 [64%]), regional lymph nodes (11 [14%]), submandibular gland (5 [7%]), inner canthus of eye (2 [3%]), and lung (2 [3%]); and single specimens from palate, jaw, shoulder, paranasal sinus, floor of mouth, ear canal, and effusion. Cytologic diagnoses included MEC (30 cases [39%]), suspicious for MEC (16 [21%]), non-MEC carcinoma (9 [12%]), suspicious for malignancy (SM) (2 [3%], malignant (M) (1 [1%]), SG and/or suspicious SG neoplasm (7 [8%]), atypical (3 [5%]), nonneoplastic (5 [6%]), nondiagnostic (2 [3%]), and benign SG neoplasm (1 [1%]). A total of 26% of low-grade (LG) cases were diagnosed as malignant in contrast to 87% malignant in high-grade (HG) cases. Cytomorphology depended on tumor grade. LG MEC contained intra- and/or extra-cellular mucin and more uniform cell and/or nuclear morphology, whereas cytologic atypia, anisonucleosis, and keratotic cells were more typical of HG tumors.
CONCLUSION
A malignant (M) or suspicious for malignancy (SM) cytologic interpretation was made in 76% of mucoepidermoid carcinoma (MEC) cases. In contrast to high-grade MEC (97% identified as M/SM), only 59% of low-grade (LG) MEC cases were interpreted as such, illustrating the continued diagnostic challenge posed by LG MEC using fine-needle aspiration biopsy.
Topics: Adult; Aged; Aged, 80 and over; Biopsy, Fine-Needle; Carcinoma, Mucoepidermoid; Humans; Middle Aged; Mucins; Salivary Gland Neoplasms; Submandibular Gland; Young Adult
PubMed: 35640091
DOI: 10.1002/cncy.22600 -
Radiology Oct 2022
Topics: Breast; Carcinoma, Mucoepidermoid; Humans
PubMed: 35787204
DOI: 10.1148/radiol.220128 -
International Journal of Molecular... Jan 2023Patients with advanced/recurrent mucoepidermoid carcinoma (MEC) have a poor prognosis. This study aimed to establish and characterize human mucoepidermoid carcinoma cell...
Patients with advanced/recurrent mucoepidermoid carcinoma (MEC) have a poor prognosis. This study aimed to establish and characterize human mucoepidermoid carcinoma cell lines from the initial surgical specimen and biopsy specimen upon recurrence from the same patient to provide a resource for MEC research. MEC specimens from the initial surgical procedure and biopsy upon recurrence were used to establish cell lines. The established cell lines were cytogenetically characterized using multi-color fluorescence in situ hybridization and detection, and the sequence of the chimeric gene was determined. Furthermore, the susceptibility of head and neck mucoepidermoid carcinoma to standard treatment drugs such as cisplatin, 5-fluorouracil, and cetuximab was investigated. We successfully established unique MEC cell lines, AMU-MEC1, from an initial surgical specimen and AMU-MEC1-R1 and AMU-MEC1-R2 from the recurrent biopsy specimen in the same patient. These cell lines exhibited epithelial morphology and developed in vitro-like cobblestones. They shared eight chromosomal abnormalities, including der(19)ins(19;11)(p13;?), which resulted in a chimeric gene, indicating the same origin of the cell lines. The susceptibility of all cell lines to cisplatin and 5-fluorouracil was low. Interestingly, EGFR dependency for cell growth decreased in AMU-MEC-R1 and AMU-MEC-R2 but was retained in AMU-MEC1. These cytogenetic and biochemical findings suggest that the established cell lines can be used to investigate the disease progression mechanisms and develop novel therapeutics for MEC.
Topics: Humans; DNA-Binding Proteins; Trans-Activators; Carcinoma, Mucoepidermoid; In Situ Hybridization, Fluorescence; Cisplatin; Transcription Factors; Biopsy; Cell Line, Tumor; Fluorouracil; Salivary Gland Neoplasms; Oncogene Proteins, Fusion
PubMed: 36675234
DOI: 10.3390/ijms24021722 -
Histopathology Jan 2023Mucoepidermoid carcinoma (MEC) is historically defined by a mix of squamoid, intermediate, and mucous cells, but we have recently encountered several cases lacking...
Mucoepidermoid carcinoma may be devoid of squamoid cells by immunohistochemistry: expanding the histologic and immunohistochemical spectrum of MAML2- rearranged salivary gland tumours.
Mucoepidermoid carcinoma (MEC) is historically defined by a mix of squamoid, intermediate, and mucous cells, but we have recently encountered several cases lacking immunoreactivity for squamous markers p40, p63, and CK5/6 despite MAML2 fusions. This study will characterise these unique tumours. Ten MEC were collected arising from the parotid gland (n = 4), submandibular gland (n = 2), nasopharynx (n = 1), base of tongue (n = 1), bronchus (n = 1), and trachea (n = 1). Six tumours were low-grade, two intermediate-grade, one high-grade, and one demonstrated low-grade areas with high-grade transformation. Four cases were oncocytic, four had clear-cell features, two had spindle cell features, and one high-grade MEC had prominent solid, cord-like, and micropapillary features. The tumours were negative for p40 (10/10), p63 (10/10), and CK5/6 (9/9). Targeted RNA sequencing demonstrated CRTC1::MAML2 in five cases, CRTC3::MAML2 in two, and a novel MAML2::CEP126 in the unusual high-grade case. In two cases with insufficient RNA, MAML2 fluorescence in situ hybridisation (FISH) showed rearrangement. Genetically-confirmed MEC may lack overt squamous differentiation by histology and immunohistochemistry. While most cases harboured canonical fusions and fit within the spectra of MEC variants with oncocytic, clear cell, and/or spindle cell features, one had a novel MAML2::CEP126 fusion and unusual morphology. In MEC without squamoid cells, the use of immunohistochemistry may hinder, rather than aid, the correct diagnosis. In such cases, MAML2 analysis is most useful. The historical definition of MEC as a carcinoma with squamoid, intermediate and mucous cells should be revisited.
Topics: Humans; Carcinoma, Mucoepidermoid; Immunohistochemistry; Salivary Gland Neoplasms; Carcinoma, Squamous Cell; Trans-Activators
PubMed: 36208053
DOI: 10.1111/his.14817 -
Frontiers in Oncology 2022Esophageal mucoepidermoid carcinoma (EMEC) is a rare disease. The biological behavior and treatment of this malignancy are not well established. (Review)
Review
BACKGROUND
Esophageal mucoepidermoid carcinoma (EMEC) is a rare disease. The biological behavior and treatment of this malignancy are not well established.
METHODS
Data from 58 patients with EMEC who underwent esophagectomy were retrospectively analyzed and compared with 5028 patients with esophageal squamous cell carcinoma (ESCC). Kaplan-Meier and multivariate Cox regression analyses were conducted to investigate the association between clinicopathological factors and survival.
RESULTS
The study cohort included 36 males and 22 females with a median age of 59 years (range, 40-78 years). Of the 47 patients who underwent preoperative esophagoscopic biopsy, only 1 patient was diagnosed with EMEC. EMEC was more often found in female patients (39.7% versus 25.8%, P=0.036) and patients with EMEC had a significantly lower rate of lymph node metastasis (25.0% versus 49.4%, P<0.001) than patients with ESCC. After 1:1 propensity score matching, the 5-year overall survival rate of 55.2% for patients with EMEC was similar to that of 61.9% for patients with ESCC (P=0.399).
CONCLUSIONS
EMEC is a rare disease that more often affects females and these patients has less lymph node metastasis than patients with ESCC. Preoperative esophagoscopic biopsy has difficulty obtaining an accurate pathological diagnosis for EMEC patients. The prognosis for EMEC is similar to that for ESCC.
PubMed: 35494060
DOI: 10.3389/fonc.2022.836352 -
Pathology Oncology Research : POR 2023Although the expression of tight junction protein claudins (CLDNs) is well known in common histological subtypes of lung cancer, it has not been investigated in rare...
Although the expression of tight junction protein claudins (CLDNs) is well known in common histological subtypes of lung cancer, it has not been investigated in rare lung cancers. The aim of our study was to examine the expression of different CLDNs in pulmonary salivary gland tumors. 35 rare lung cancers including pathologically confirmed 12 adenoid cystic carcinomas (ACCs) and 23 mucoepidermoid carcinomas (MECs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and CLDN1, -2, -3, -4, -5, -7, and -18 protein expressions were analyzed. The levels of immunopositivity were determined with H-score. Certain pathological characteristics of ACC and MEC samples (tumor grade, presence of necrosis, presence of blood vessel infiltration, and degree of lymphoid infiltration) were also analyzed. CLDN overexpression was observed in both tumor types, especially in CLDN2, -7, and -18 IHC. Markedly different patterns of CLDN expression were found for ACC and MEC tumors, especially for CLDN1, -2, -4, and -7, although none of these trends remained significant after correction for multiple testing. Positive correlations between expressions of CLDN2 and -5, CLDN3 and -4, and CLDN5 and -18 were also demonstrated. Tumors of never-smokers presented lower levels of CLDN18 than tumors of current smokers (-value: 0.003). This is the first study to comprehensively describe the expression of different CLDNs in lung ACC and MEC. Overexpression of certain CLDNs may pave the way for targeted anti-claudin therapy in these rare histological subtypes of lung cancer.
Topics: Retrospective Studies; Humans; Male; Female; Middle Aged; Claudins; Carcinoma, Adenoid Cystic; Mucoepidermoid Tumor; Immunohistochemistry; Lung Neoplasms; Transcriptome
PubMed: 37621953
DOI: 10.3389/pore.2023.1611328 -
Histopathology Mar 2022To investigate the histological diversity of salivary mucoepidermoid carcinoma (MEC), its clinicopathological features, and its associations with CRTC1/3-MAML2 fusions. (Comparative Study)
Comparative Study
AIMS
To investigate the histological diversity of salivary mucoepidermoid carcinoma (MEC), its clinicopathological features, and its associations with CRTC1/3-MAML2 fusions.
METHODS AND RESULTS
Salivary MEC cases (n = 177) were examined for CRTC1/3-MAML2 fusions, histological variants were classified, and tumours were graded according to four different grading systems. Adverse histological features considered to be unusual in MEC were also investigated. Of the 177 MEC cases, 110 were positive for CRTC1/3-MAML2 fusions. The classical variant was the most frequent in the fusion-positive case group, the fusion-negative case group, and the total case group. The clear/oncocytic variant was the second most frequent in the fusion-positive and total case groups. Oncocytic, Warthin-like and spindle variants were seen in the fusion-positive case group only. Clear cell, sclerosing, mucinous and central variants were seen in both the fusion-positive case group and the fusion-negative case group. No case was classified as a ciliated variant, as a mucoacinar variant, or as a high-grade transformation. As compared with the classical variant, non-classical variants were characterised by frequent CRTC1/3-MAML2 fusions and a low clinical stage in all cases. Of the four histological features considered to be unusual in MEC, marked nuclear atypia, frequent mitoses (>10/10 high-power fields) and extensive necrosis were found independently of the fusion status, and were present in 3-5% of all cases. However, none of the cases showed overt keratinisation. On comparison, the Armed Forces Institute of Pathology and modified Healey grading systems downgraded tumours, the Brandwein system upgraded tumours, and the Memorial Sloan Kettering system provided a moderate means of assessment.
CONCLUSION
Recognition of the histological diversity of MEC, its clinicopathological features and its associations with CRTC1/3-MAML2 fusions is helpful for an accurate diagnosis of this carcinoma.
Topics: Carcinoma, Mucoepidermoid; Female; Gene Fusion; Humans; Male; Neoplasm Grading; Salivary Gland Neoplasms; Trans-Activators; Transcription Factors
PubMed: 34657306
DOI: 10.1111/his.14586 -
Frontiers in Oncology 2022Mucoepidermoid carcinoma is dominant in salivary glands and rarely occurs in the lung. Primary pulmonary mucoepidermoid carcinoma is a type of non-small-cell lung...
BACKGROUND
Mucoepidermoid carcinoma is dominant in salivary glands and rarely occurs in the lung. Primary pulmonary mucoepidermoid carcinoma is a type of non-small-cell lung cancer, but the prognostic factors in Chinese patients remain controversial. This investigation aimed to review cases of pulmonary mucoepidermoid carcinoma, analyse the prognosis of this disease.
METHODS
Patients with pathologically proven pulmonary mucoepidermoid carcinoma were screened at the Department of Respiratory and Critical Care Medicine at the Peking University Third Hospital, Beijing Friendship Hospital Affiliated to Capital Medical University, and Peking University Cancer Hospital for inclusion in this retrospective study. Demographic data, including age, sex, clinical symptoms, smoking, alcohol consumption, allergies, family history, imaging findings, fibrobronchoscopy findings, surgical procedures, tumour location and pathologic stage, were collected. Telephone follow-up was conducted for all patients not lost to follow-up. The associations of sex, age, smoking, tumour differentiation, tumour size, lymph node metastasis, pathologic stage, and patient survival were retrospectively analysed. Kaplan-Meier, univariate and multivariate analysis curves were used to analyse patient prognosis and prognostic factors.
RESULTS
Thirty-one patients, comprising 23 males and 8 females, were enrolled in the analysis. The mean age was 60.77 ± 11.44 years. The first symptom was nonspecific, with cough being the most common (21/31, 67.77%); smokers accounted for 16 of the 31 patients, and ten patients had a history of alcohol consumption. Overall, the tumours could occur in either lobe of the lungs; tumours occurred in the right lung in 19/31 patients, and tumours occurred in the left lung in 12/31 patients. Regarding TNM stage, 10 patients had stage I (5 with stage 1a, 5 with stage 1b), 5 had stage II (1 with stage 2a, 4 with stage 2b), 3 had stage III (1 with stage 3a, 2 with stage 3b), and 13 had stage IV (10 with stage 4a, 3 with stage 4b). In our Cox univariate survival analysis of patients with pulmonary mucoepidermoid carcinoma, we found that TNM stage IV, degree of differentiation and lymph node metastasis were risk factors for pulmonary mucoepidermoid carcinoma and that degree of differentiation was an independent risk factor.
CONCLUSION
The clinical, radiographical and pathological features of pulmonary mucoepidermoid carcinoma were systemically analysed and summarized, and the degree of differentiation and lymph node metastasis, as well as prognostic factors in addition to clinical stage, were confirmed.
PubMed: 36119481
DOI: 10.3389/fonc.2022.916906 -
Head and Neck Pathology Apr 2024Salivary gland tumors (SGTs) are rare and highly heterogeneous lesions, making diagnosis a challenging activity. In addition, the small number of studies and samples... (Review)
Review
BACKGROUND
Salivary gland tumors (SGTs) are rare and highly heterogeneous lesions, making diagnosis a challenging activity. In addition, the small number of studies and samples evaluated difficults the determination of prognosis and diagnosis. Despite the solid advances achieved by research, there is still an intense need to investigate biomarkers for diagnosis, prognosis and that explain the evolution and progression of SGTs.
METHODS
We performed a comprehensive literature review of the molecular alterations focusing on the most frequent malignant SGTs: mucoepidermoid carcinoma and adenoid cystic carcinoma.
RESULTS
Due to the importance of biomarkers in the tumorigenenic process, this review aimed to address the mechanisms involved and to describe molecular and biomarker pathways to better understand some aspects of the pathophysiology of salivary gland tumorigenesis.
CONCLUSIONS
Molecular analysis is essential not only to improve the diagnosis and prognosis of the tumors but also to identify novel driver pathways in the precision medicine scenario.
Topics: Carcinoma, Mucoepidermoid; Humans; Carcinoma, Adenoid Cystic; Salivary Gland Neoplasms; Biomarkers, Tumor
PubMed: 38658430
DOI: 10.1007/s12105-024-01629-2