Yonsei Med J.  2016 Mar;57(2):482-489. 10.3349/ymj.2016.57.2.482.

Expression of Autophagy and Reactive Oxygen Species-Related Proteins in Lacrimal Gland Adenoid Cystic Carcinoma

• Koo JS
• Kim JW
• Yoon JS

• KMID: 2374057
• DOI: http://doi.org/10.3349/ymj.2016.57.2.482

Abstract

PURPOSE
To investigate the difference of expression of autophagy and reactive oxygen species (ROS) related proteins in adenoid cystic carcinoma (ACC) of lacrimal gland in comparison with ACC of salivary gland.
MATERIALS AND METHODS
Formalin-fixed, paraffin-embedded tissue samples from patients pathologically diagnosed as lacrimal gland ACC (n=11) and salivary gland ACC (n=64) were used. Immunochemistry was used to measure expression of autophagy related proteins [beclin-1, light chain (LC) 3A, LC3B, p62, and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)] and ROS related proteins [catalase, thioredoxinreductase, glutathione S-transferasepi (GSTpi), thioredoxin interacting protein, and manganese superoxide dismutase (MnSOD)]. The prognostic factors related to disease-free and overall survival (OS) in lacrimal gland ACC by log-rank tests, were determined.
RESULTS
GSTpi in stromal cells was more highly expressed in lacrimal gland ACC (p=0.006), however, MnSOD in epithelial cells was expressed more in salivary gland ACC (p=0.046). LC3B positivity and BNIP3 positivity in epithelial component were associated with shorter disease-free survival (both p=0.002), and LC3A positivity in stromal component was the factor related to shorter OS (p=0.005).
CONCLUSION
This is the first study to demonstrate the expression of autophagy and ROS related proteins in lacrimal gland ACC in comparison with the salivary gland ACC, which would provide a basis for further study of autophagy and ROS mechanism as novel therapeutic targets in lacrimal gland ACC.

Keyword

Adenoid cystic carcinoma; autophagy; lacrimal gland; reactive oxygen species; salivary gland

MeSH Terms

Adult
Aged
*Autophagy
Beclin-1
Biomarkers, Tumor/metabolism
Carcinoma, Adenoid Cystic/*metabolism/pathology
Carrier Proteins
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
Humans
Lacrimal Apparatus/metabolism/pathology
Lacrimal Apparatus Diseases/*metabolism/pathology
Male
Membrane Proteins
Middle Aged
Proto-Oncogene Proteins
Reactive Oxygen Species/*metabolism
Salivary Gland Neoplasms/metabolism/*pathology
Salivary Glands/pathology
Beclin-1
Biomarkers, Tumor
Carrier Proteins
Membrane Proteins
Proto-Oncogene Proteins
Reactive Oxygen Species

Figure

• 

  Fig. 1 Immunohistochemical expression of GSTpi and MnSOD in lacrimal and salivary gland adenoid cystic carcinoma (ACC). Expression of GST in stromal component was higher and MnSOD in cell component was lower in lacrimal gland ACC than in salivary gland ACC (×100). GSTpi, glutathione S-transferasepi; MnSOD, manganese superoxide dismutase; H&E, hematoxylin and eosin.

• 

  Fig. 2 Kaplan-Meier curves for disease-free survival and overall survival of lacrimal gland ACC, correlated with expression of the autophagy related proteins such as LC3A, LC3B, and BNIP3. BNIP3, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3; ACC, adenoid cystic carcinoma; LC, light chain.

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