Mucoepidermoid carcinoma of the salivary glands: A reappraisal of the influence of tumor differentiation on prognosis

Clode, A.; Fonseca, Isabel; Santos, Jorge Rosa; Soares, Jorge

doi:10.1002/jso.2930460207

Cited by 61 publications

(35 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Numb immunoreactivity may provide a simple and reliable parameter to more Tumor grade is considered a useful prognostic parameter for both MECs (18,20,22) ACCs (7-8, 16, 21). Despite a statistically significant correlation of low tumor grade and diffuse Numb immunoreactivity, the latter retained an independent prognostic value for DFS at multivariate analysis, for both ACC and MEC.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Implications of Numb Immunoreactivity in Salivary Gland Carcinomas

Maiorano

Pece

Resta

et al. 2007

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

The gene numb encodes for a protein (Numb) involved in cell fate decisions in Drosophila, with proposed endocytic and developmental functions in mammalians. The distribution pattern of Numb in human tissues however, has not been fully characterized. We set out to explore the immunohistochemical expression of Numb in normal and neoplastic (28 adenoid cystic and 34 mucoepidermoid carcinomas) salivary glands, and correlated the results with the clinico-pathologic features of the neoplasms. Intense Numb immunoreactivity was detected in normal ductal cells and in a subset of acinar cells. In salivary carcinomas, we detected diffuse and intense Numb immunostaining in 5 adenoid cystic and 8 mucoepidermoid carcinomas. By contrast, the majority of adenoid cystic and mucoepidermoid cancers showed only moderate (14 and 5 cases) or focal staining (9 and 21 cases), respectively. The corresponding expression of Numb mRNA was documented in normal parotid gland and adenoid cystic carcinoma. Numb immunoreactivity was inversely correlated with the histological grade and Ki-67 immunoreactivity of both adenoid cystic and mucoepidermoid carcinomas. In addition, while tumor grade, stage, Ki-67 and Numb immunoreactivity were associated with disease-free survival in univariate analysis, only Numb and Ki-67 immunoreactivities retained independent prognostic significance in multivariate analysis. These data suggest that loss of Numb is implicated in aberrant differentiation programs of salivary gland carcinomas and may serve as a prognostic indicator in patients treated for these neoplasms.

show abstract

Section: Discussionmentioning

confidence: 99%

Prognostic Implications of Numb Immunoreactivity in Salivary Gland Carcinomas

Maiorano

Pece

Resta

et al. 2007

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

show abstract

“…The clinical behavior of MEC has proved to be difficult to predict but correlations to tumor grade and stage have been reported [30][31][32][33].The histologic features that are most useful in predicting the aggressive nature of these tumors are: 1) a minor cystic component (less than 20%); 2) tumor necrosis; 3) neural invasion; 4) cellular anaplasia; and 5) brisk mitotic activity [29]. Based on the presence or absence of these features and the clinical behavior, MEC are classified as low, intermediate, and high grade.…”

Section: Mucoepidermoid Carcinomamentioning

confidence: 99%

Current Thinking on Malignant Salivary Gland Neoplasms

Arrangoiz¹

2013

JCTR

View full text Add to dashboard Cite

Abstract:Malignant salivary gland neoplasms are rare, representing approximately 3% to 7% of all head and neck cancers. Contrasting from the more common mucosal head and neck cancers, which, in general, are ascribed to excessive tobacco, alcohol use, and more recently to viral infection, specific carcinogenic factors for malignant salivary gland growths have not been as clearly identified. Histologically, they represent a heterogeneous group of tumors. Forty histologic types of epithelial tumors of the salivary glands have been reported; some are exceedingly rare and may be the topic of only a few case reports. Salivary tumors can arise in the major salivary glands or in one of the minor salivary glands (predominantly mucus secreting glands), which are distributed throughout the upper aerodigestive. Most patients who develop malignant salivary gland tumors are in the sixth or seventh decade of life. FNA should be considered as part of the diagnostic evaluation but due to its varying sensitivities and specificities imaging modalities such as ultrasound, CT scans, and MRI should also be used as diagnostic adjuncts. Surgery is the primary modality for management of these tumors, nontraditional surgical approaches and instrumentation, as well as facial nerve monitoring, can be selectively utilized to try and decrease the morbidity associated with these surgical procedures. Adjuvant treatment is primarily achieved with radiation therapy. Chemotherapy continues to have a palliative role in the management of salivary gland tumors; however, research in this field is trying to identify a therapeutic role for chemotherapy in order to improve overall survival.

show abstract

“…Cells were seeded at a density of 1×10 4 per well and incubated overnight. LB100 was then added to the medium, and the cells were incubated for 4 hours.…”

Section: Glycolytic and Mitochondrial Respiration Rate Measurementsmentioning

confidence: 99%

“…Although most cases are low-/medium-grade lesions, 15.1% of cases are classified as highgrade lesions and are ineligible for systemic treatment, leading to a poor prognosis with a 5-year survival rate of 47.2% [3,4]. Surgery is the mainstay for the treatment of high-grade MEC.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Protein Phosphatase 2A Sensitizes Mucoepidermoid Carcinoma to Chemotherapy via the PI3K-AKT Pathway in Response to Insulin Stimulus

Liu¹,

Wang²,

Cui³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase that mediates cell cycle regulation and metabolism. Mounting evidence has indicated that PP2A inhibition exhibits considerable anticancer potency in multiple types of human cancers. However, the efficacy of PP2A inhibition remains unexplored in mucoepidermoid carcinoma (MEC), especially in locally advanced and metastatic cases with limited systemic treatment. In this study, we demonstrated the therapeutic potency of LB100 in mucoepidermoid carcinoma. Methods: In this study, the expression of PP2A was evaluated using immunohistochemical (IHC) staining. The effects associated with LB100 alone and in combination with cisplatin for the treatment of mucoepidermoid carcinoma were investigated both in vitro, regarding metabolism, proliferation, and migration, and in vivo in a mucoepidermoid carcinoma xenograft model. In addition, with LB100 treatment and in response to an insulin stimulus, the expression levels and phosphorylation levels of targets in the PI3K-AKT pathway were determined using western blot analysis and immunoblotting. Results: The expression of protein phosphatase 2A was significantly upregulated in the clinical specimens of high-grade MECs compared with those of low-/medium-grade MECs and normal controls. In this article, we report that a small molecule PP2A inhibitor, LB100, decreased cellular viability and glycolytic activity and induced G2/M cell cycle arrest. Importantly, LB100 enhanced the efficacy of cisplatin in mucoepidermoid carcinoma cells both in vitro and in vivo. PP2A inhibition by LB100 increased the phosphorylation of insulin receptor substrate 1(IRS-1) on serine residues, downregulated the expression of phosphatidylinositol 3-kinase (PI3K) p110 alpha subunit and dephosphorylated AKT at Ser473 and Thr308 in mucoepidermoid carcinoma cells in response to insulin stimulus. Conclusion: These results highlight the translational potential of PP2A inhibition to synergize with cisplatin in mucoepidermoid carcinoma treatment.

show abstract

Mucoepidermoid carcinoma of the salivary glands: A reappraisal of the influence of tumor differentiation on prognosis

Cited by 61 publications

References 17 publications

Prognostic Implications of Numb Immunoreactivity in Salivary Gland Carcinomas

Prognostic Implications of Numb Immunoreactivity in Salivary Gland Carcinomas

Current Thinking on Malignant Salivary Gland Neoplasms

Inhibition of Protein Phosphatase 2A Sensitizes Mucoepidermoid Carcinoma to Chemotherapy via the PI3K-AKT Pathway in Response to Insulin Stimulus

Contact Info

Product

Resources

About