Yonsei Med J.  2018 Aug;59(6):717-726. 10.3349/ymj.2018.59.6.717.

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

• Bazarsad S
• Kim JY
• Zhang X
• Kim KY
• Lee DY
• Ryu MH
• Kim J

• KMID: 2415530
• DOI: http://doi.org/10.3349/ymj.2018.59.6.717

Abstract

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.

Keyword

Adenoid cystic carcinoma; ataxia telangiectasia mutated (ATM); p53; prognostic marker; salivary gland

MeSH Terms

Adenoids*
Ataxia Telangiectasia
Biomarkers
Carcinoma, Adenoid Cystic*
Humans
Kaplan-Meier Estimate
Neoplasm Metastasis
Prognosis
Recurrence
Salivary Glands*
Survival Rate
Biomarkers

Figure

• 

  Fig. 1 Myb expression in ACC. (A) Negative control was obtained by the omission of Myb antibody in ACC. (B) Myb expression was not detected in non-tumoural salivary gland parenchyma. (C) Myb expression in ACC, solid type. Myb expression was detected in myoepithelial cells, but not in ductal cells (indicated by the black arrow). (D) Myb expression in ACC, tubular and cribriform types. Original magnification of all figures: ×400. ACC, adenoid cystic carcinoma.

• 

  Fig. 2 ATM expression in ACC. (A) Negative control was obtained by the omission of ATM antibody. (B) Positive control: ATM antibody-specific staining was performed in human lymph nodes. (C) ATM expression was observed in the nuclei of acinar and ductal cells in normal salivary glands. (D) ATM positivity in cancer cells and stromal fibroblasts. (E) ATM was positive in cancer cells and negative in stromal fibroblasts. (F) ATM was positive in stromal fibroblasts and negative in cancer cells. (G) ATM was negative in both cancer cells and stromal fibroblasts. Original magnification of all figures: ×200. Inset: original magnification ×1000. ATM, ataxia telangiectasia mutated; ACC, adenoid cystic carcinoma.

• 

  Fig. 3 Overall survival rates according to ATM expression in cancer cells (A) and stromal fibroblasts (B). Metastasis-free survival rates according to ATM expression in cancer cells (C) and stromal fibroblasts (D). ATM, ataxia telangiectasia mutated; ACC, adenoid cystic carcinoma.

• 

  Fig. 4 Expression of p53 and phospho-p53 (S15) in adenoid cystic carcinoma. Positive expression of p53 (A) and negative expression of p53 (B). Positive expression of phospho-p53 (S15) (C) and negative expression of phospho-p53 (S15) (D). Original magnification of all figures: ×200. Inset: original magnification ×1000.

• 

  Fig. 5 Overall survival rates of ACC patients according to the expression of p53, phospho-p53 (S15), ATM given positive p53 expression, and ATM given negative phospho-p53 (S15) expression. (A) Overall survival according to p53 expression. (B) Overall survival according to phospho-p53 (S15) expression. (C) Overall survival according to the expression of ATM given positive p53 expression. (D) Overall survival according to the expression of ATM given negative phospho-p53 (S15) expression. ATM, ataxia telangiectasia mutated; ACC, adenoid cystic carcinoma.

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