Expression of metabolism-related proteins in lacrimal gland adenoid cystic carcinoma

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Citation: AMERICAN JOURNAL OF CLINICAL PATHOLOGY, Vol.143(4) : 584-592, 2015

MeSH: Adult ; Aged ; Amino Acid Transport System ASC/metabolism ; Biomarkers, Tumor/metabolism* ; Carcinoma, Adenoid Cystic/metabolism* ; Carcinoma, Adenoid Cystic/pathology ; Disease-Free Survival ; Eye Neoplasms/metabolism* ; Eye Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic* ; Glutaminase/metabolism ; Glycine Hydroxymethyltransferase/metabolism ; Humans ; Immunohistochemistry ; Lacrimal Apparatus/metabolism ; Lacrimal Apparatus/pathology ; Lacrimal Apparatus Diseases/metabolism* ; Lacrimal Apparatus Diseases/pathology ; Male ; Middle Aged ; Minor Histocompatibility Antigens ; Monocarboxylic Acid Transporters/metabolism ; Muscle Proteins/metabolism ; Prognosis ; Salivary Gland Neoplasms/metabolism* ; Salivary Gland Neoplasms/pathology ; Salivary Glands/metabolism ; Salivary Glands/pathology ; Young Adult

Keywords: Adenoid cystic carcinoma ; Lacrimal gland ; Metabolism-related protein ; Protein expression ; Salivary gland

Abstract: OBJECTIVES: To investigate the expression and the clinical implications of metabolism-related proteins in lacrimal gland adenoid cystic carcinoma (ACC) in comparison with salivary gland ACC.

METHODS: Human tissue samples of lacrimal gland ACC (n = 11) and salivary gland ACC (n = 64) were analyzed. Immunochemistry was used to measure expression of proteins related to glycolysis (glucose transporter 1, hexokinase II, carbonic anhydrase IX, and monocarboxylate transporter 4 [MCT4]), glutaminolysis (glutaminase 1 [GLS1], glutamate dehydrogenase [GDH], and amino acid transporter 2 [ASCT2]), mitochondria (adenosine triphosphate [ATP] synthase, succinate dehydrogenase A [SDHA], and succinate dehydrogenase B), and glycolytic intermediate metabolism (phosphoserine phosphatase [PSPH], serine hydroxymethyl transferase 1 [SHMT1]).

RESULTS: GLS1 and ASCT2 were more highly expressed, and GDH, ATP synthase, and SDHA were expressed to a lesser degree in lacrimal gland ACC than in salivary gland ACC (P < .05). Lacrimal gland ACC showed less of a mitochondrial phenotype than did salivary gland ACC (P = .001). Positivity of MCT4 and PSPH was related to shorter disease-free survival, and SHMT1 was related to shorter overall survival (P < .05).

CONCLUSIONS: Lacrimal gland ACC exhibited higher expression of GLS1 and ASCT2, compared with salivary gland ACC. Overexpression of MCT4, PSPH, and SHMT1 was associated with poorer prognosis.