Tiefenböck-Hansson Katharina, Haapaniemi Aaro, Farnebo Lovisa, Palmgren Björn, Tarkkanen Jussi, Farnebo Marianne, Munck-Wikland Eva, Mäkitie Antti, Garvin Stina, Roberg Karin
Division of Otorhinolaryngology and Head and Neck Surgery, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Oncol Rep. 2017 Oct;38(4):2062-2068. doi: 10.3892/or.2017.5898. Epub 2017 Aug 11.
The current treatment recommendation for T2-3N0M0 glottic squamous cell carcinoma (SCC) in the Nordic countries comprises of radiotherapy (RT) and chemoradiotherapy (CRT). Tumor radiosensitivity varies and another option is primary surgical treatment, which underlines the need for predictive markers in this patient population. The aim of the present study was to investigate the relation of the proteins WRAP53β, survivin and p16INK4a to RT/CRT response and ultimate outcome of patients with T2-T3N0 glottic SCC. Protein expression was determined using immunohistochemistry on tumors from 149 patients consecutively treated with RT or CRT at Helsinki University Hospital, Karolinska University Hospital, and Linköping University Hospital during 1999-2010. Our results demonstrate a significantly better 5-year relapse-free survival, disease-free survival (DFS), disease-specific survival and overall survival of patients with T3N0 tumors treated with CRT compared with RT alone. Patients with tumors showing a cytoplasmic staining of WRAP53β revealed significantly worse DFS compared with those with nuclear staining. For survivin, we observed a trend towards better 5-year DFS in patients with strong nuclear survivin expression compared with those with weak nuclear survivin expression (p=0.091). Eleven (7%) tumors showed p16 positivity, with predilection to younger patients, and this age group of patients with p16-positive SCC had a significantly better DFS compared with patients with p16-negative SCC. Taken together, our results highlight WRAP53β as a potential biomarker for predicting RT/CRT response in T2-T3N0 glottic SCC. p16 may identify a small but distinct group of glottic SCC with favorable outcome. Furthermore, for T3N0 patients better outcome was observed following CRT compared to RT alone.
北欧国家目前对T2-3N0M0声门鳞状细胞癌（SCC）的治疗建议包括放射治疗（RT）和放化疗（CRT）。肿瘤的放射敏感性各不相同，另一种选择是原发性手术治疗，这突出了在该患者群体中寻找预测标志物的必要性。本研究的目的是调查蛋白质WRAP53β、survivin和p16INK4a与T2-T3N0声门SCC患者的RT/CRT反应及最终预后的关系。使用免疫组织化学方法对1999年至2010年期间在赫尔辛基大学医院、卡罗林斯卡大学医院和林雪平大学医院连续接受RT或CRT治疗的149例患者的肿瘤进行蛋白质表达测定。我们的结果表明，与单纯RT相比，接受CRT治疗的T3N0肿瘤患者的5年无复发生存率、无病生存率（DFS）、疾病特异性生存率和总生存率显著更好。与细胞核染色的患者相比，肿瘤显示WRAP53β细胞质染色的患者DFS显著更差。对于survivin，我们观察到细胞核survivin强表达的患者与弱表达的患者相比，有5年DFS更好的趋势（p=0.091）。11例（7%）肿瘤显示p16阳性，多见于年轻患者，该年龄组p16阳性SCC患者的DFS显著优于p16阴性SCC患者。综上所述，我们的结果突出了WRAP53β作为预测T2-T3N0声门SCC患者RT/CRT反应的潜在生物标志物。p16可能识别出一小群但独特的预后良好的声门SCC。此外，对于T3N0患者，与单纯RT相比，CRT后的预后更好。
