Riechelmann Herbert, Steinbichler Teresa Bernadette, Sprung Susanne, Santer Matthias, Runge Annette, Ganswindt Ute, Gamerith Gabriele, Dudas Jozsef
Department for Otorhinolaryngology, Head and Neck Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Cancers (Basel). 2021 Feb 12;13(4):772. doi: 10.3390/cancers13040772.
EMT promotes radio- and chemotherapy resistance in HNSCC in vitro. As EMT has been correlated to the transcription factor Slug in tumor specimens from HNSCC patients, we assessed whether Slug overexpression predicts radio- and chemotherapy resistance and favors upfront surgery in HNSCC patients. Slug expression was determined by IHC scoring in tumor specimens from patients with incident HNSCC. Patients were treated with either definitive radiotherapy or chemoradiotherapy (primary RT/CRT) or upfront surgery with or without postoperative RT or CRT (upfront surgery/PORT). Treatment failure rates and overall survival (OS) were compared between RT/CRT and upfront surgery/PORT in Slug-positive and Slug-negative patients. Slug IHC was positive in 91/354 HNSCC patients. Primary RT/CRT showed inferior response rates (univariate odds ratio (OR) for treatment failure, 3.6; 95% CI, 1.7 to 7.9; = 0.001) and inferior 5-year OS (univariate, < 0.001) in Slug-positive patients. The independent predictive value of Slug expression status was confirmed in a multivariable Cox model ( = 0.017). Slug-positive patients had a 3.3 times better chance of survival when treated with upfront surgery/PORT versus primary RT/CRT. For HNSCC patients, Slug IHC represents a novel and feasible predictive biomarker to support upfront surgery.
上皮-间质转化（EMT）在体外促进头颈部鳞状细胞癌（HNSCC）的放疗和化疗抗性。由于EMT与HNSCC患者肿瘤标本中的转录因子Slug相关，我们评估了Slug过表达是否可预测HNSCC患者的放疗和化疗抗性以及是否有利于早期手术。通过免疫组化评分确定初发HNSCC患者肿瘤标本中的Slug表达。患者接受根治性放疗或放化疗（原发性放疗/放化疗）或早期手术加或不加术后放疗或放化疗（早期手术/术后放疗或放化疗）。比较Slug阳性和Slug阴性患者在放疗/放化疗和早期手术/术后放疗或放化疗之间的治疗失败率和总生存期（OS）。在354例HNSCC患者中，91例Slug免疫组化呈阳性。原发性放疗/放化疗在Slug阳性患者中显示出较低的缓解率（治疗失败的单变量优势比（OR）为3.6；95%置信区间，1.7至7.9；P = 0.001）和较差的5年总生存期（单变量，P < 0.001）。在多变量Cox模型中证实了Slug表达状态的独立预测价值（P = 0.017）。与原发性放疗/放化疗相比，Slug阳性患者接受早期手术/术后放疗或放化疗时的生存机会高3.3倍。对于HNSCC患者，Slug免疫组化是一种支持早期手术的新型且可行的预测生物标志物。
