Journal
JOURNAL OF OTOLARYNGOLOGY-HEAD & NECK SURGERY
Volume 49, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s40463-020-00446-1
Keywords
Adenoid cystic carcinoma; Myb; Beta-catenin; Prognostic indicator
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Funding
- Patrick Ha: NIH/NIDCR [R01DE023227]
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Background: Adenoid cystic carcinoma (ACC) is the second most common malignancy of the salivary glands, accounting for similar to 1% of malignant tumors of the head and neck region and 10% of salivary gland neoplasms. Predicting the long-term outcomes of patients with ACC is still challenging, as reliable prognostic biomarkers are not available. Among salivary gland tumors, Myb overexpression is highly specific for ACC. In addition, theMYB-NF1Bfusion translocation is a hallmark of ACC, and although the detection of this translocation does not appear to impact prognosis, theMYB-NF1Bfusion is also implicated in MYB upregulation. Myb has recently been identified as an activator of the Wnt/beta-catenin signaling pathway, and aberrant cytoplasmic expression of beta-catenin has been observed in many salivary gland malignancies. In this study, we aim to analyze the impact of Myb and beta-catenin expression on prognosis in ACC. Methods: A tissue microarray constructed from archival tissue from 64 patients with ACC was stained for Myb and beta-catenin; both localization and intensity were evaluated. In parallel, we abstracted demographic data, tumor characteristics, survival data, and outcomes, including local recurrence, regional recurrence, and distant metastasis from the medical record. Statistical analysis was performed. Results: Our analysis supports that ACC patients negative for Myb by immunohistochemical methods have a higher risk of developing metastasis than patients with Myb staining (HR: 4.06, 95% CI: 1.02-14.96,p-value: 0.03). Although not statistically significant, cytoplasmic localization of beta-catenin is may suggest a diminished rate of relapse-free survival (HR 2.45, 95%CI: 0.9-6.7,p = 0.08). Furthermore, Myb expression correlated with beta-catenin expression, increasing 1.69 in staining intensity units with each increase in beta-catenin staining intensity (p-value: 0.04). Conclusions: Our study suggests that Myb expression is protective; Myb positive patients have diminished risk of distant metastasis. In contrast, there is a trend towards increased hazard of death in ACC patients with cytoplasmic beta-catenin expression. Additional analyses will be necessary to establish Myb and beta-catenin as independent protective and adverse biomarkers, respectively.
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