Toll-like receptor 9 expression in mucoepidermoid salivary gland carcinoma may associate with good prognosis.
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 (TLR9) is an immune receptor recognizing microbial DNA. Its expression associates with prognosis or cancer properties in several cancers. This study examined the role of TLR9 in MEC.


METHODS
Sixty patients with salivary gland MEC were collected from two Finnish university hospitals, and tumor samples were stained for TLR9. Salivary gland high-grade MEC cell line (UT-MUC-1) was cultured to assess TLR9 and MMP-13 expression. The function of TLR9 was studied in vitro using traditional Matrigel(®) 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. TLR9 was expressed in 56 of 60 (93%) tumors. High TLR9 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, TLR9 expression was prognostically insignificant due to heavy correlation to disease stage and higher gradus. Treating UT-MUC-1 cells with TLR9 ligand CpG in vitro induced MMP-13 expression and invasion in Matrigel(®) invasion assay, whereas decreased invasion was seen in myoma organotypic model.


CONCLUSIONS
Functional TLR9 is present in salivary MEC, and high level of expression may indicate good prognosis. However, more studies are needed to evaluate biological consequences of TLR9 interaction in tumor cells.
Department of Dentistry, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu, Finland.
Johanna
J
Korvala
Teresa
T
Harjula
Kristiina
K
Siirilä
Alhadi
A
Almangush
Katri
K
Aro
Antti A
AA
Mäkitie
Reidar
R
Grénman
Tuomo J
TJ
Karttunen
Ilmo
I
Leivo
Joonas H
JH
Kauppila
Tuula
T
Salo
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D018277:Carcinoma, Mucoepidermoid / Q000737:chemistry*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000032:analysis; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009924:Organ Culture Techniques; D010307:Parotid Neoplasms / Q000737:chemistry*; D011379:Prognosis; D012189:Retrospective Studies; D013365:Submandibular Gland Neoplasms / Q000737:chemistry*; D015996:Survival Rate; D051217:Toll-Like Receptor 9 / Q000032:analysis*; D059016:Tumor Microenvironment; D055815:Young Adult
D014408:Biomarkers, Tumor; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13
mucoepidermoid carcinoma; toll-like receptor 9