title: Predictive role of Toll-like receptors 2, 4, and 9 in oral tongue squamous cell carcinoma.
abstract: OBJECTIVE
  The clinical behavior of oral tongue squamous cell carcinoma (OTSCC) can be unpredictable, and even small tumors may behave aggressively. Toll-like receptors (TLRs) are pattern-recognition molecules involved in innate immunity, and they are also expressed in many types of cancer. TLRs play an apparently pivotal role in some cancers related to tumor progression and, conversely, cancer inhibition, however their role in oral cancer is unclear. We therefore studied the expression of TLR-2, -4, -5, -7, and -9 in early-stage OTSCC.
  
  
  METHODS
  Tissue microarray technique and immunohistochemistry was employed to define the expression of TLRs from the tumors of 73 consecutive patients with Stage I-II OTSCC. Immunoexpression scores were compared with patient and tumor related characteristics and survival.
  
  
  RESULTS
  All TLRs were expressed in OTSCC tissue. High/strong TLR-2, -4, and -9 expression correlated with deeper tumor invasion. Cytoplasmic TLR-2 and -4 also correlated significantly with higher tumor grade, whereas high TLR-5 expression associated with lower tumor grade. High expression of TLR-9 correlated with advanced tumor size. Negative or mild TLR-5 expression predicted poor disease-specific survival.
  
  
  CONCLUSIONS
  All the studied TLRs showed high expression in early-stage OTSCC. More importantly, TLR-2, -4, and -9 seemed to predict invasive tumor growth.
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Central Hospital and University of Helsinki, P.O. Box 220, Haartmaninkatu 4E, FI-00029 HUS, Helsinki, Finland. Electronic address: laura.k.makinen@helsinki.fi.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Mäkinen
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Central Hospital and University of Helsinki, P.O. Box 220, Haartmaninkatu 4E, FI-00029 HUS, Helsinki, Finland. Electronic address: timo.atula@hus.fi.
authors.forename: Timo
authors.initials: T
authors.lastname: Atula
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Central Hospital and University of Helsinki, P.O. Box 220, Haartmaninkatu 4E, FI-00029 HUS, Helsinki, Finland. Electronic address: valtteri.hayry@fimnet.fi.
authors.forename: Valtteri
authors.initials: V
authors.lastname: Häyry
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Central Hospital and University of Helsinki, P.O. Box 220, Haartmaninkatu 4E, FI-00029 HUS, Helsinki, Finland. Electronic address: lauri.jouhi@helsinki.fi.
authors.forename: Lauri
authors.initials: L
authors.lastname: Jouhi
authors.affiliation: Department of Pathology, Haartman Institute, University of Helsinki, P.O. Box 21, Haartmaninkatu 3, FI-00014 University of Helsinki, Helsinki, Finland. Electronic address: neeta.datta@helsinki.fi.
authors.forename: Neeta
authors.initials: N
authors.lastname: Datta
authors.affiliation: Department of Pathology, Haartman Institute, University of Helsinki, P.O. Box 21, Haartmaninkatu 3, FI-00014 University of Helsinki, Helsinki, Finland. Electronic address: sanna.h.lehtonen@helsinki.fi.
authors.forename: Sanna
authors.initials: S
authors.lastname: Lehtonen
authors.affiliation: Institute of Dentistry, Biomedicum 1, University of Helsinki, P.O. Box 63, Haartmaninkatu 8, FI-00014 University of Helsinki, Helsinki, Finland. Electronic address: abdirisak.ahmed@helsinki.fi.
authors.forename: Abdirisak
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Central Hospital and University of Helsinki, P.O. Box 220, Haartmaninkatu 4E, FI-00029 HUS, Helsinki, Finland. Electronic address: antti.makitie@helsinki.fi.
authors.forename: Antti A
authors.initials: AA
authors.lastname: Mäkitie
authors.affiliation: Department of Surgery, Helsinki University Central Hospital, Haartmaninkatu 4, P.O. Box 440, FI-00029 HUS, Helsinki, Finland; Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O. Box 440, FI-00014 University of Helsinki, Helsinki, Finland. Electronic address: caj.haglund@hus.fi.
authors.forename: Caj
authors.initials: C
authors.lastname: Haglund
authors.affiliation: Department of Pathology, Haartman Institute, University of Helsinki, P.O. Box 21, Haartmaninkatu 3, FI-00014 University of Helsinki, Helsinki, Finland; Department of Pathology, HUSLAB, Helsinki University Central Hospital, P.O. Box 400, Haartmaninkatu 3, FI-00029 HUS, Helsinki, Finland. Electronic address: jaana.hagstrom@hus.fi.
authors.forename: Jaana
authors.initials: J
authors.lastname: Hagström
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051193:Toll-Like Receptors / Q000502:physiology*; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D051193:Toll-Like Receptors
keywords: Immunohistochemistry; Invasion; Metastasis; Oral cancer; Prognosis; Recurrence; Survival; Tongue carcinoma; p16 protein