Clinicopathologic implications of Myb and Beta-catenin expression in adenoid cystic carcinoma
Abstract Background Adenoid cystic carcinoma (ACC) is the second most common malignancy of the salivary glands, accounting for ~ 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 rel...
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SAGE Publishing
2020-07-01
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| Series: | Journal of Otolaryngology - Head and Neck Surgery |
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| Online Access: | http://link.springer.com/article/10.1186/s40463-020-00446-1 |
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| author | Susan Park Manali Vora Annemieke van Zante Joseph Humtsoe Hyun-Su Kim Sue Yom Shweta Agarwal Patrick Ha |
| author_facet | Susan Park Manali Vora Annemieke van Zante Joseph Humtsoe Hyun-Su Kim Sue Yom Shweta Agarwal Patrick Ha |
| author_sort | Susan Park |
| collection | DOAJ |
| description | Abstract Background Adenoid cystic carcinoma (ACC) is the second most common malignancy of the salivary glands, accounting for ~ 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, the MYB-NF1B fusion translocation is a hallmark of ACC, and although the detection of this translocation does not appear to impact prognosis, the MYB-NF1B fusion is also implicated in MYB upregulation. Myb has recently been identified as an activator of the Wnt/β-catenin signaling pathway, and aberrant cytoplasmic expression of β-catenin has been observed in many salivary gland malignancies. In this study, we aim to analyze the impact of Myb and β-catenin expression on prognosis in ACC. Methods A tissue microarray constructed from archival tissue from 64 patients with ACC was stained for Myb and β-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 β-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 β-catenin expression, increasing 1.69 in staining intensity units with each increase in β-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 β-catenin expression. Additional analyses will be necessary to establish Myb and β-catenin as independent protective and adverse biomarkers, respectively. |
| format | Article |
| id | doaj-art-e5e6fb674816437abcd786844676e6b6 |
| institution | OA Journals |
| issn | 1916-0216 |
| language | English |
| publishDate | 2020-07-01 |
| publisher | SAGE Publishing |
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| series | Journal of Otolaryngology - Head and Neck Surgery |
| spelling | doaj-art-e5e6fb674816437abcd786844676e6b62025-08-20T01:47:50ZengSAGE PublishingJournal of Otolaryngology - Head and Neck Surgery1916-02162020-07-014911810.1186/s40463-020-00446-1Clinicopathologic implications of Myb and Beta-catenin expression in adenoid cystic carcinomaSusan Park0Manali Vora1Annemieke van Zante2Joseph Humtsoe3Hyun-Su Kim4Sue Yom5Shweta Agarwal6Patrick Ha7Columbia University College of Dental MedicineDepartment of Otolaryngology Head and Neck Surgery, University of California San FranciscoDepartment of Pathology, University of California San FranciscoDepartment of Otolaryngology Head and Neck Surgery, University of California San FranciscoDepartment of Otolaryngology Head and Neck Surgery, University of California San FranciscoDepartment of Radiation Oncology, University of California San FranciscoDepartment of Pathology, University of New Mexico School of MedicineDepartment of Otolaryngology Head and Neck Surgery, University of California San FranciscoAbstract Background Adenoid cystic carcinoma (ACC) is the second most common malignancy of the salivary glands, accounting for ~ 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, the MYB-NF1B fusion translocation is a hallmark of ACC, and although the detection of this translocation does not appear to impact prognosis, the MYB-NF1B fusion is also implicated in MYB upregulation. Myb has recently been identified as an activator of the Wnt/β-catenin signaling pathway, and aberrant cytoplasmic expression of β-catenin has been observed in many salivary gland malignancies. In this study, we aim to analyze the impact of Myb and β-catenin expression on prognosis in ACC. Methods A tissue microarray constructed from archival tissue from 64 patients with ACC was stained for Myb and β-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 β-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 β-catenin expression, increasing 1.69 in staining intensity units with each increase in β-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 β-catenin expression. Additional analyses will be necessary to establish Myb and β-catenin as independent protective and adverse biomarkers, respectively.http://link.springer.com/article/10.1186/s40463-020-00446-1Adenoid cystic carcinomaMybBeta-cateninPrognostic indicator |
| spellingShingle | Susan Park Manali Vora Annemieke van Zante Joseph Humtsoe Hyun-Su Kim Sue Yom Shweta Agarwal Patrick Ha Clinicopathologic implications of Myb and Beta-catenin expression in adenoid cystic carcinoma Journal of Otolaryngology - Head and Neck Surgery Adenoid cystic carcinoma Myb Beta-catenin Prognostic indicator |
| title | Clinicopathologic implications of Myb and Beta-catenin expression in adenoid cystic carcinoma |
| title_full | Clinicopathologic implications of Myb and Beta-catenin expression in adenoid cystic carcinoma |
| title_fullStr | Clinicopathologic implications of Myb and Beta-catenin expression in adenoid cystic carcinoma |
| title_full_unstemmed | Clinicopathologic implications of Myb and Beta-catenin expression in adenoid cystic carcinoma |
| title_short | Clinicopathologic implications of Myb and Beta-catenin expression in adenoid cystic carcinoma |
| title_sort | clinicopathologic implications of myb and beta catenin expression in adenoid cystic carcinoma |
| topic | Adenoid cystic carcinoma Myb Beta-catenin Prognostic indicator |
| url | http://link.springer.com/article/10.1186/s40463-020-00446-1 |
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