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Mcl-1、血管内皮生长因子-R2和14-3-3σ的表达可能预测局部晚期头颈部鳞状细胞癌患者对放疗和化疗的初始反应。

Mcl-1, vascular endothelial growth factor-R2, and 14-3-3sigma expression might predict primary response against radiotherapy and chemotherapy in patients with locally advanced squamous cell carcinomas of the head and neck.

作者信息

Erovic Boban M, Pelzmann Martina, Grasl Matthäus Ch, Pammer Johannes, Kornek Gabriela, Brannath Werner, Selzer Edgar, Thurnher Dietmar

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, Division of Oncology and Medical Statistics, Center of Excellence for Clinical and Experimental Oncology, University of Vienna Medical School, Vienna, Austria.

出版信息

Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8632-6. doi: 10.1158/1078-0432.CCR-05-1170.

Abstract

PURPOSE

This study was done to explore whether the expression of a selected set of proteins could predict primary response to radiotherapy or concomitant radiotherapy and chemotherapy in patients with advanced head and neck cancer.

EXPERIMENTAL DESIGN

Forty-three pretreatment tumor biopsies were taken during diagnostic panendoscopy and examined for Mcl-1, vascular endothelial growth factor (VEGF)-R2, CD9, and 14-3-3sigma expression by immunohistochemistry. Forty-three patients underwent primary radiotherapy, of which, 29 patients received concomitant chemotherapy (low dose daily cisplatin, mitomycin C bolus). The primary end-point was locoregional tumor control 6 months after completion of radiotherapy. Mcl-1, VEGF-R2, CD9, and 14-3-3sigma expression were correlated with patients' primary response to radiotherapy and chemotherapy and with established clinicopathologic variables.

RESULTS

Thirty complete and 13 partial responses were observed in our patient group. High expression levels of Mcl-1 (P=0.021), VEGF-R2 (P=0.032), and 14-3-3sigma (P=0.013), but not of CD9, in tumor biopsies was correlated with complete response. Overexpression of at least two of the three aforementioned proteins in pretreatment biopsies predicted-with a likelihood of 80%-whether a patient would achieve complete response to radiotherapy and chemotherapy. However, if only one of these proteins is overexpressed, there is a likelihood of 84.6% that this patient would not completely respond to therapy.

CONCLUSION

Determining the expression levels of Mcl-1, VEGF-R2, and 14-3-3sigma may be helpful in predicting the early clinical response in head and neck tumor patients receiving primary radiotherapy and chemotherapy and may further allow a pretherapeutic selection of patients.

摘要

目的

本研究旨在探讨一组特定蛋白质的表达是否能够预测晚期头颈癌患者对放射治疗或同步放化疗的初始反应。

实验设计

在诊断性全腔镜检查期间获取43份治疗前肿瘤活检样本,通过免疫组织化学检测Mcl-1、血管内皮生长因子(VEGF)-R2、CD9和14-3-3σ的表达。43例患者接受了根治性放疗,其中29例患者接受了同步化疗(每日低剂量顺铂、丝裂霉素C推注)。主要终点是放疗结束后6个月的局部区域肿瘤控制情况。Mcl-1、VEGF-R2、CD9和14-3-3σ的表达与患者对放疗和化疗的初始反应以及既定的临床病理变量相关。

结果

在我们的患者组中观察到30例完全缓解和13例部分缓解。肿瘤活检样本中Mcl-1(P=0.021)、VEGF-R2(P=0.032)和14-3-3σ(P=0.013)的高表达水平与完全缓解相关,但CD9的高表达与完全缓解无关。治疗前活检样本中上述三种蛋白质中至少两种的过表达预测患者对放疗和化疗达到完全缓解的可能性为80%。然而,如果这些蛋白质中只有一种过表达,那么该患者不完全缓解的可能性为84.6%。

结论

确定Mcl-1、VEGF-R2和14-3-3σ的表达水平可能有助于预测接受根治性放疗和化疗的头颈肿瘤患者的早期临床反应,并可能进一步实现患者的治疗前选择。

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