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 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 βcatenin expression. Additional analyses will be necessary to establish Myb and β-catenin as independent protective and adverse biomarkers, respectively.

Extracting Potential New Targets for Treatment of Adenoid Cystic Carcinoma Using Bioinformatic Methods

“…The substantial participation of some of the twenty hub genes, such as TP53 18 , NOTCH1 19 , CTNNB1 20 , MET 5 , and KIT 21 in the ACC tumorigenesis, has already been studied. The others need future studies to clarify their role in the ACC.…”

Quantitative ubiquitylomics reveals the ubiquitination regulation landscape in oral adenoid cystic carcinoma

“…Surgery and postoperative radiotherapy are the standard treatment of ACC for a long time [6] with poor prognosis (up to 40% of recurrent rate and 60% of metastatic rate) [7]. Several factors had been studied to associate with the clinicopathological parameters and prognosis of ACC, including p53 [8], SOX2 [9], mutated ATM [10], MACC1 [11], WHSC1 [12], EpCAM [13], PSMA [14], TRAF6 [15], HSP27 [16], PRRX1 [17], hypoxia-related genes [18], the EGFR pathway genes [19], MYB-NFIB fusion genes [20][21][22][23], as well as NOTCH1-HEY1 pathway [24] and Akt signaling pathway [25,26]. Considering the aggressive behavior, it is urgent to figure out more efficient clinical pathological and biomolecular prognostic factors for therapeutic choices.…”