Zoltan Laszló, Farkas Robert, Schally Andrew V, Pozsgai Eva, Papp Andras, Bognár Laura, Tornoczki Tamas, Mangel Laszlo, Bellyei Szabolcs
Department of Oncology, University of Pécs, Edesanyak street 17, Pécs, 7624, Hungary.
Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs, Hungary.
Pathol Oncol Res. 2019 Jan;25(1):279-288. doi: 10.1007/s12253-017-0342-z. Epub 2017 Nov 4.
The aim of the present study was to investigate the relationship between the intensity of biomarker expression and the response to radiochemotherapy in patients with advanced esophageal squamous cell cancer (ESCC). Ninety-two patients with locally advanced ESCC were examined retrospectively. Pre-treatment tumor samples were stained for proteins SOUL, Hsp 16.2, Growth Hormone-Releasing Hormone Receptor (GHRH-R) and p-Akt using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationship between intensity of expression of biomarkers and clinical parameters and 3-year OS. A significant correlation was found between high intensity staining for Hsp 16.2, p-Akt and SOUL and poor response to NRCT. Application of a higher dose of radiation and higher dose of cisplatin resulted in better clinical and histopathological responses, respectively. Among the clinical parameters, the localization of the tumor in the upper-third of the esophagus and less than 10% weight loss were independent prognostic factors for increased 3-year OS. Hsp16.2, p-Akt and SOUL are predictors of negative response to NRCT, therefore these biomarkers may become promising targets for therapy. Furthermore, level of expression of p-Akt, weight loss and the localization of the tumor are significant factors in the prediction of OS in ESCC.
本研究的目的是调查晚期食管鳞状细胞癌（ESCC）患者生物标志物表达强度与放化疗反应之间的关系。对92例局部晚期ESCC患者进行回顾性检查。采用免疫组织化学方法对治疗前肿瘤样本进行SOUL、Hsp 16.2、生长激素释放激素受体（GHRH-R）和p-Akt蛋白染色。采用Kaplan-Meier曲线显示生物标志物表达强度与临床参数及3年总生存期（OS）之间的关系。发现Hsp 16.2、p-Akt和SOUL高强度染色与新辅助放疗化疗（NRCT）反应不佳之间存在显著相关性。应用更高剂量的放疗和更高剂量的顺铂分别导致更好的临床和组织病理学反应。在临床参数中，肿瘤位于食管上三分之一处以及体重减轻少于10%是3年OS增加的独立预后因素。Hsp16.2、p-Akt和SOUL是NRCT阴性反应的预测指标，因此这些生物标志物可能成为有前景的治疗靶点。此外，p-Akt的表达水平、体重减轻和肿瘤定位是预测ESCC患者OS的重要因素。
