Mäkinen Laura K, Atula Timo, Häyry Valtteri, Jouhi Lauri, Datta Neeta, Lehtonen Sanna, Ahmed Abdirisak, Mäkitie Antti A, Haglund Caj, Hagström Jaana
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.
Department of Pathology, Haartman Institute, University of Helsinki, P.O. Box 21, Haartmaninkatu 3, FI-00014 University of Helsinki, Helsinki, Finland.
Oral Oncol. 2015 Jan;51(1):96-102. doi: 10.1016/j.oraloncology.2014.08.017. Epub 2014 Sep 26.
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.
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.
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.
All the studied TLRs showed high expression in early-stage OTSCC. More importantly, TLR-2, -4, and -9 seemed to predict invasive tumor growth.
口腔舌鳞状细胞癌(OTSCC)的临床行为难以预测,即使是小肿瘤也可能具有侵袭性。Toll样受体(TLR)是参与固有免疫的模式识别分子,在多种癌症中也有表达。TLR在一些与肿瘤进展相关的癌症中以及相反地在癌症抑制中似乎起着关键作用,然而它们在口腔癌中的作用尚不清楚。因此,我们研究了TLR-2、-4、-5、-7和-9在早期OTSCC中的表达。
采用组织芯片技术和免疫组化方法确定73例连续的I-II期OTSCC患者肿瘤中TLR的表达。将免疫表达评分与患者及肿瘤相关特征和生存率进行比较。
所有TLR均在OTSCC组织中表达。TLR-2、-4和-9的高/强表达与肿瘤浸润深度相关。细胞质TLR-2和-4也与较高的肿瘤分级显著相关,而TLR-5的高表达与较低的肿瘤分级相关。TLR-9的高表达与肿瘤大小较大相关。TLR-5阴性或轻度表达预示疾病特异性生存率较差。
所有研究的TLR在早期OTSCC中均呈高表达。更重要的是,TLR-2、-4和-9似乎可预测肿瘤的侵袭性生长。