Ataxia-Telangiectasia-Mutated Protein Expression as a Prognostic Marker in Adenoid Cystic Carcinoma of the Salivary Glands

PURPOSE: Adenoid cystic carcinoma (ACC) is a high-grade malignant tumor of the salivary glands, clinically characterized by multiple recurrences and late distant metastasis. Biological markers for assessing the prognosis of ACC have remained elusive. The purpose of this study was to investigate whether the protein expressions of ataxia telangiectasia mutated (ATM), p53, and ATM-mediated phosphorylated p53 are related to patient survival in ACC. MATERIALS AND METHODS: In this study, 48 surgical samples were used to assess the expressions of ATM and its downstream target p53. Fisher's exact test and Kaplan-Meier analysis were conducted to evaluate the role of ATM, p53, and phospho-p53 (S15) protein expressions in predicting patient survival and distant metastasis. RESULTS: Myb expression was positive in 85.4% of ACCs, but did not reflect patient survival rate. In contrast, low expression of ATM in cancer cells was significantly correlated with poor survival rate (p=0.037). Moreover, under positive p53 expression, low expression of ATM was highly predictive of poor survival in ACC (p=0.017). CONCLUSION: These data indicate that combined assessment of ATM and p53 expression can serve as a useful prognostic marker for assessing survival rate in patients with ACC of the salivary glands.

Ataxia-telangiectasia-mutated protein expression as a prognostic marker in adenoid cystic carcinoma of salivary glands / Шинэ санаа Шинэ нээлт

@#Adenoid cystic carcinoma (ACC) is one of the high grade malignant tumors in salivary glands, prognosticallycharacterized by multiple recurrences and late distant metastasis. Recently, Myb-NFIB fusion or rearrangements of Myb have been detected as a hallmark of ACC. However, no biological marker estimating the outcome of ACC has been proven yet. Purpose of this study was to investigate whether the protein expression of ATM gene is related to patients’ survival in ACC. This study consists of 48 surgical samples for detecting expression of ATM and its downstream p53. Kaplan-Meier plots were used to evaluate the relationship between the protein expression ratios of ATM, p53 and its ATM-mediated phosphorylation and the overall survival rate of patients with ACC. low expression of ATM in cancer cells correlated with poor survival rate (p = 0.037). However, low expression of ATM in stromal fibroblasts was not significantly associated with patient outcome. Moreover, this study evaluated ATM expression stratified by p53 and its ATM-mediated phosphorylation status. ATM loss was associated with a significantly decreased overall survival in patients simultaneously showing overexprssion of p53 (p = 0.01) and low expression of p53 phospho S15 (p = 0.05). These data supported that loss of ATM and its functional status in p53 pathway is an important factor associated with poor outcome of patients in ACC of salivary glands.