Yoshida Kosuke, Suzuki Shiro, Sakata Jun, Utsumi Fumi, Niimi Kaoru, Yoshikawa Nobuhisa, Nishino Kimihiro, Shibata Kiyosumi, Kikkawa Fumitaka, Kajiyama Hiroaki
Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Showa-ku, Nagoya 466-8550, Japan.
Department of Obstetrics and Gynecology, Banbuntane Hotokukai Hospital, Nakagawa-ku, Nagoya 454-8509, Japan.
Oncol Lett. 2018 Jul;16(1):515-521. doi: 10.3892/ol.2018.8610. Epub 2018 May 2.
Vascular endothelial growth factor (VEGF) inhibitors have been utilized for the treatment against advanced or recurrent cervical carcinoma as a novel therapeutic modality. However, the expression level of VEGF in post-radiotherapy relapsed/persistent cervical cancer remains to be elucidated. The aim of the present study was to investigate the expression of VEGF and associated molecules using tumor samples from patients with post-radiotherapy relapsed/persistent cervical cancer. From a database of 826 patients who were treated at our institution between 2003 and 2015, eight patients with post-radiotherapy relapsed/persistent cervical cancer were identified, and 20 patients who underwent initial surgery alone were used as a control. Using samples from these patients, the expression levels of VEGF-A, VEGF receptor-1 (VEGFR-1) and hypoxia inducible factor-1α (HIF-1α) were immunohistochemically categorized as negative or weakly, moderately, or strongly positive according to the size of the staining area, and intensity. In carcinoma cells, the expression levels of VEGF-A, VEGFR-1 and HIF-1α were significantly higher in post-radiotherapy relapsed/persistent cervical cancer compared with control patients (P=0.0003, 0.0003, and 0.0001, respectively). In stroma cells, similar tendencies with statistical significance were observed (P=0.0014 and P<0.0001, respectively). In addition, the expression levels of VEGF-A and VEGFR-1 in carcinoma cells were significantly correlated with each other (P<0.0001). A significantly higher expression of VEGF was identified in post-radiotherapy relapsed/persistent cervical cancer compared with typical specimens from cervical cancer. The findings provide a novel insight into the clinical treatment for recurrent/persistent cervical cancer using a VEGF antagonist.
血管内皮生长因子(VEGF)抑制剂已作为一种新型治疗方式用于治疗晚期或复发性宫颈癌。然而,放疗后复发/持续性宫颈癌中VEGF的表达水平仍有待阐明。本研究的目的是利用放疗后复发/持续性宫颈癌患者的肿瘤样本,研究VEGF及相关分子的表达情况。从2003年至2015年在我院接受治疗的826例患者的数据库中,确定了8例放疗后复发/持续性宫颈癌患者,并将20例仅接受初始手术的患者作为对照。使用这些患者的样本,根据染色区域大小和强度,通过免疫组织化学将VEGF-A、VEGF受体-1(VEGFR-1)和缺氧诱导因子-1α(HIF-1α)的表达水平分类为阴性或弱阳性、中度阳性或强阳性。在癌细胞中,与对照患者相比,放疗后复发/持续性宫颈癌中VEGF-A、VEGFR-1和HIF-1α的表达水平显著更高(分别为P = 0.0003、0.0003和0.0001)。在基质细胞中,观察到具有统计学意义的相似趋势(分别为P = 0.0014和P < 0.0001)。此外,癌细胞中VEGF-A和VEGFR-1的表达水平彼此显著相关(P < 0.0001)。与典型宫颈癌标本相比,放疗后复发/持续性宫颈癌中VEGF的表达明显更高。这些发现为使用VEGF拮抗剂治疗复发性/持续性宫颈癌的临床治疗提供了新的见解。