Cancer Res Treat.  2018 Oct;50(4):1064-1073. 10.4143/crt.2017.337.

The Prognostic Significance of Notch1 and Fatty Acid Binding Protein 7 (FABP7) Expression in Resected Tracheobronchial Adenoid Cystic Carcinoma: A Multicenter Retrospective Study

Affiliations
  • 1Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. mianxie@gird.cn
  • 2Department of General Surgery, Sun-Yet Sen University Cancer Center, Guangzhou, China.
  • 3Department of Thoracic Surgery, The First Affiliated Hospital, Sun-Yet Sen University, Guangzhou, China.
  • 4Department of Internal Medicine, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China.
  • 5Department of Thoracic Surgery, The First Affiliated Hospital, Tsing Hua University, Beijing, China.
  • 6Department of Medical Statistics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 7Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Abstract

PURPOSE
Adenoid cystic carcinoma (ACC) of the trachea and bronchus is a rare tumor. Although MYB-NFIB oncogene fusion and Notch1 mutation have been identified in ACC, little is known about the expression and clinical significance of Notch1 and its target gene fatty acid binding protein 7 (FABP7) in tracheobronchial ACC.
MATERIALS AND METHODS
Primary tracheobronchial ACC that were resected between 1998 and 2014 were identified through the pathology and oncology database from five thoracic oncology centers in China. A tissue array was constructed from the patients' samples and the expressions of Notch1 and FABP7 were evaluated by immunohistochemistry. The association between the expression of both markers and survival was determined.
RESULTS
Overexpression of Notch1 and FABP7, detected in 37.8% and 38.3% of 368 patients with tracheobronchial ACC, respectively, was an independent prognostic indicator for recurrencefree survival (RFS) by multivariable Cox proportional hazard model (p=0.032 and p=0.048, respectively). Overexpression of Notch1, but not of FABP7, predicted overall survival (OS) (p=0.018). When categorized into four groups according to coexpression of Notch1 and FABP7, patients with overexpression of both Notch1 and FABP7 belonged to the group with the shortest RFS and OS (p=0.01 and p=0.048, respectively).
CONCLUSION
Expression of Notch1 and FABP7, and coexpression of Notch1 and FABP7, is strongly associated with poor survival in resected tracheobronchial ACC. These data are consistent with the hypothesis that poor differentiation of tracheobronchial ACC correlates with the activation of Notch signaling.

Keyword

Adenoid cystic carcinoma; Prognosis; Bronchi; Trachea; Notch1; FABP7

MeSH Terms

Adenoids*
Bronchi
Carcinoma, Adenoid Cystic*
Carrier Proteins*
China
Humans
Immunohistochemistry
Oncogene Fusion
Pathology
Prognosis
Proportional Hazards Models
Retrospective Studies*
Trachea
Carrier Proteins

Figure

  • Fig. 1. Representative immunohistochemical staining intensity of Notch1 (left column) and FABP7 (right column) in patients with tracheobronchial adenoid cystic carcinoma. 0, no staining; 1+, mild; 2+, moderate; 3+, strong intensity of staining (×200).

  • Fig. 2. Kaplan-Meier analysis of recurrence-free survival (RFS) in patients with tracheobronchial adenoid cystic carcinoma. (A) RFS in patients with Notch1 low versus high expression. (B) RFS in patients with FABP7 low versus high expression.

  • Fig. 3. Kaplan-Meier analysis of overall survival (OS) in patients with tracheobronchial adenoid cystic carcinoma. (A) OS in patients with Notch1 low versus high expression. (B) OS in patients with FABP7 low versus high expression.

  • Fig. 4. Kaplan-Meier analysis of recurrence-free survival in patients with tracheobronchial adenoid cystic carcinoma stratified according to the expression of both Notch1 and FABP7.

  • Fig. 5. Kaplan-Meier analysis of overall survival in patients with tracheobronchial adenoid cystic carcinoma stratified according to the expression of both Notch1 and FABP7.


Reference

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