Expression and significance of notch signaling pathway in salivary adenoid cystic carcinoma

Bell, Diana; Hanna, Ehab Y.; Miele, Lucio; Roberts, Dianna B.; Weber, Randal S.; El‐Naggar, Adel K.

doi:10.1016/j.anndiagpath.2013.10.001

Cited by 29 publications

(25 citation statements)

References 22 publications

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“…Given these findings, it is possible that FABP7 expression is regulated by the Notch signaling pathway in ACC. These results are intriguing in light of another study showing that NOTCH1 immunostaining was similar to what we observed here for FABP7 [39] . If this is the case, FABP7 may be a useful biomarker to measure response to Notch inhibitors in salivary tumors.…”

Section: Discussionsupporting

confidence: 90%

Fatty Acid Binding Protein 7 Is a Molecular Marker in Adenoid Cystic Carcinoma of the Salivary Glands: Implications for Clinical Significance

Phuchareon

Overdevest

McCormick

et al. 2014

Translational Oncology

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Adenoid cystic carcinoma (ACC) is an aggressive malignant neoplasm of the salivary glands. Its diagnosis is difficult due to overlapping features with other salivary tumors. Gene expression analysis may complement traditional diagnostic methods. We searched gene expression patterns in the Gene Expression Omnibus (GEO) database and in our tumor and normal samples. The biologic and prognostic potential of the identified genes was analyzed. The GEO data set of primary xenografted ACCs revealed that expression of five genes, engrailed homeobox 1 (EN1), fatty acid binding protein 7 (FABP7), hemoglobin epsilon 1, MYB, and versican (VCAN), was dramatically increased. mRNA expression of EN1, FABP7, MYB, and VCAN distinguished our sporadic ACCs from normal tissues and benign tumors. FABP7 expression appeared to be regulated differently from EN1 and MYB and was crossly correlated with poor prognosis in our ACC cohort. Immunohistochemistry showed that FABP7 protein was predominantly expressed in the nucleus of myoepithelial cells of both tubular and cribriform subtypes. In contrast, in the solid subtype, which is often associated with a lower survival rate, FABP7 protein was uniformly expressed in cancerous cells. One case with cribriform architecture and the highest level of FABP7 mRNA showed strong FABP7 staining in both duct-type epithelial and myoepithelial cells, suggesting that diffuse expression of FABP7 protein might be related to aggressive tumor behavior and poor prognosis. We propose FABP7 as a novel biomarker in ACC. The molecule may be useful in diagnosis and for identifying more effective therapies targeting this protein or upstream molecules that regulate it.

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Section: Discussionsupporting

confidence: 90%

Fatty Acid Binding Protein 7 Is a Molecular Marker in Adenoid Cystic Carcinoma of the Salivary Glands: Implications for Clinical Significance

Phuchareon

Overdevest

McCormick

et al. 2014

Translational Oncology

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“…mRNA profiling indicated the overexpression of several genes within the PI3K, MAPK, Wnt, and Notch pathways. Specifically, our screen detected several genes known to be overexpressed or mutated in ACC, including MYB, P53, and NOTCH1 (46). Many of the genes detected as overexpressed in our samples (i.e., FGFR1, JAG1, and expressing checkpoint receptors Lag-3, Tim-3, and PD-1 over the course of chemoradiation.…”

Section: Discussionmentioning

confidence: 99%

Immune Profiling of Adenoid Cystic Carcinoma: PD-L2 Expression and Associations with Tumor-Infiltrating Lymphocytes

Sridharan

Gjini

Liao

et al. 2016

Cancer Immunology Research

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Adenoid cystic carcinoma (ACC) is among the most lethal salivary gland tumors, with no treatments for metastatic disease that prolong survival. We examined tissue from 28 primary and metastatic ACC deposits obtained from 21 patients for infiltrating immune cells and PD-L1/PD-L2 expression and determined mRNA profiles of over 1,400 oncogenic and immune-related genes. We also assessed the effect of chemoradiation on immune mediators in a patient who had serial biopsies available. Most tumors expressed PD-L2 but had few infiltrating immune cells.Lack of immune-cell infiltrate was associated with expression of genes in the b-catenin/Wnt and PI3K pathways. Additionally, certain transcripts linked to growth and invasion were differentially expressed among primary and metastatic deposits. Chemoradiation appeared to increase CD8 þ effector T cells, decrease regulatory T cells, and promote a systemic humoral response. These data suggest a potential role for PD-L2 inhibition and immune modulation as treatment for patients with ACC.

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“…Although a number of mutations were unique or only in a small fraction of the tumors, the altered genes could be grouped together by their potential to disrupt specific cellular functions or biochemical pathways. This included those that interact with the MYB transcription network, but also genes that influence chromatin remodeling, DNA damage/checkpoint responses, signaling pathways regulated by fibroblast growth factor (FGF)‐insulin‐like growth factor‐PI3K, protein kinase A pathway, or Notch 24, 25, 35, 36. Understanding the specific contribution of each mutation to tumorigenesis might lead to novel pathways for targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

Chakraborty²,

et al. 2015

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BackgroundAdenoid cystic carcinoma (ACC) is a rare tumor of secretory glands. In this study, recent advances in molecular characterization and in therapeutics are reviewed.MethodsA search of articles in PubMed and of abstracts from national meetings was performed regarding ACC.ResultsRecent genetic analyses found that recurrent chromosome 6:9 translocations in ACC generate an MYB:NFIB gene fusion resulting in overexpression of the MYB oncoprotein. Several other frequent mutations are recently published that may be relevant for drug development. Several trials of targeted drugs are reviewed. Some agents delay tumor progression, but tumor responses remain rare.ConclusionACCs have a characteristic chromosomal translocation, but also frequently pick up additional mutations. Clinical research is limited by the rarity and slow growth of ACC. Several ongoing trials are testing agents that inhibit fibroblast growth factor receptor signaling or other signaling pathways. Novel treatments based on the recently sequenced tumor genome are under development. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. 38: 620–627, 2016

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Expression and significance of notch signaling pathway in salivary adenoid cystic carcinoma

Cited by 29 publications

References 22 publications

Fatty Acid Binding Protein 7 Is a Molecular Marker in Adenoid Cystic Carcinoma of the Salivary Glands: Implications for Clinical Significance

Fatty Acid Binding Protein 7 Is a Molecular Marker in Adenoid Cystic Carcinoma of the Salivary Glands: Implications for Clinical Significance

Immune Profiling of Adenoid Cystic Carcinoma: PD-L2 Expression and Associations with Tumor-Infiltrating Lymphocytes

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

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