Combined Expression of Cyclin B1 and Cytoplasmic HMGB1 Is Associated With Delayed Cervical Lymph Node Metastasis in Early-Stage Tongue Squamous Cell Carcinoma.

OBJECTIVE: Delayed cervical lymph node metastasis is strongly associated with poor prognosis in early-stage tongue squamous cell carcinoma, but useful biomarkers remain limited. This study evaluated cyclin B1, high-mobility group box protein 1 and 2, and proliferating cell nuclear antigen for stratifying the risk of delayed cervical lymph node metastasis. METHODS: Eighty-two patients with Stage I/II tongue squamous cell carcinoma who underwent partial glossectomy without elective neck dissection were included. Cyclin B1 and the cytoplasmic expression of the other three markers were assessed immunohistochemically. Cutoff values were determined using receiver operating characteristic analysis. Cervical lymph node metastasis-free survival was estimated using Kaplan-Meier and multivariable Cox analyses. RESULTS: Cyclin B1 showed the strongest association with delayed cervical lymph node metastasis (χ2 = 29.0, p < 0.0001; area under the curve, 0.80; sensitivity, 84.0%; specificity, 77.2%). Dual positivity for cyclin B1 and cytoplasmic high-mobility group box protein 1 showed 76.0% sensitivity and 87.7% specificity and remained significantly associated with metastasis-free survival after adjustment for pathological depth of invasion and Yamamoto-Kohama classification (adjusted hazard ratio, 8.57; 95% confidence interval, 3.44-24.36; p < 0.0001). CONCLUSIONS: Combined cyclin B1 and cytoplasmic high-mobility group box protein 1 assessment may aid postoperative risk stratification.