Prognostic Value of Heterotypic Neutrophil-in-Tumor Structure in Tongue Squamous Cell Carcinoma Patients

Abstract Objective : To analyze the prognostic value of frequency of heterotypic neutrophil-in-tumor structure(FNiT) in patients with tongue squamous cell carcinoma(TSCC). Methods : In vitro, we cocultured TSCC cell line-CAL33 with neutrophils to form heterotypic neutrophil-in-tumor structures, which were then subject to fluorescence staining. Clinically, 197 patients were enrolled. Information including age, sex, FNiT, ECOG PS(Performance Status), FH (family history) of cancer, complications, and pathological characteristics such as tumor stage, node stage, metastasis, disease stage, lymphovascular invasion, perineural invasion, tumor grade, and follow-up results was extracted and analyzed. Results : Fluorescent staining results of typical heterotypic neutrophil-in-tumor structure showed that well-differentiated CAL-33-2 had stronger ability to internalize more neutrophils than poorly-differentiated CAL-33-1 did, the latter often internalizing only one neutrophil. The mean FNiT was 4.8‰,with a range from 2.1‰ to 8.9‰. The FNiT was significantly associated with tumor stage, disease stage and tumor grade. A total of 119 patients died of the disease, and the 5-year disease-specific survival(DSS) rate was 36%. The median survival time was 52.6 months. In patients with an FNiT<4.8‰, the 5-year DSS rate was 40%; in patients with an FNiT>=4.8‰, the 5-year DSS was 28%, and the difference was significant(P=0.001). Cox model analysis showed that FNiT along with disease stage, lymphovascular invasion and tumor grade was an independent prognostic factor for DSS. Conclusion : The FNiT as a novel predictor is positively correlated with adverse prognosis of patients with TSCC.