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Toll‐like receptor 9 expression in mucoepidermoid salivary gland carcinoma may associate with good prognosis
Author(s) -
Korvala Johanna,
Harjula Teresa,
Siirilä Kristiina,
Almangush Alhadi,
Aro Katri,
Mäkitie Antti A.,
Grénman Reidar,
Karttunen Tuomo J.,
Leivo Ilmo,
Kauppila Joonas H.,
Salo Tuula
Publication year - 2014
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12160
Subject(s) - tlr9 , salivary gland , mucoepidermoid carcinoma , cancer , malignancy , salivary gland cancer , pathology , cancer research , biology , matrigel , medicine , receptor , oncology , angiogenesis , gene expression , dna methylation , biochemistry , gene
Background Mucoepidermoid carcinoma ( MEC ) is the most common salivary gland malignancy. Although several biomarkers have been evaluated, histological grade remains the most valuable prognostic marker. Toll‐like receptor 9 ( TLR 9) is an immune receptor recognizing microbial DNA . Its expression associates with prognosis or cancer properties in several cancers. This study examined the role of TLR 9 in MEC . Methods Sixty patients with salivary gland MEC were collected from two F innish university hospitals, and tumor samples were stained for TLR 9. Salivary gland high‐grade MEC cell line ( UT ‐ MUC ‐1) was cultured to assess TLR 9 and MMP ‐13 expression. The function of TLR 9 was studied in vitro using traditional M atrigel ® invasion assay and novel human myoma organotypic model. Results Cancer‐specific survival was related with tumor grade ( P = 0.01), and there were no deaths in patients with low‐grade MEC . TLR 9 was expressed in 56 of 60 (93%) tumors. High TLR 9 expression indicated better survival in the patient series ( P = 0.002) and showed a trend for association with lower disease stage ( P = 0.06) and higher differentiation grade ( P = 0.068). In multivariate analysis, TLR 9 expression was prognostically insignificant due to heavy correlation to disease stage and higher gradus. Treating UT ‐ MUC ‐1 cells with TLR 9 ligand CpG in vitro induced MMP ‐13 expression and invasion in M atrigel ® invasion assay, whereas decreased invasion was seen in myoma organotypic model. Conclusion Functional TLR 9 is present in salivary MEC , and high level of expression may indicate good prognosis. However, more studies are needed to evaluate biological consequences of TLR 9 interaction in tumor cells.