Sobajima Jun, Kumamoto Kensuke, Haga Norihiro, Tamaru Junichi, Takahashi Takeo, Miyazaki Tatsuya, Ishida Hideyuki
Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama.
Oncol Lett. 2012 Feb;3(2):287-292. doi: 10.3892/ol.2011.468. Epub 2011 Nov 2.
Chemoradiotherapy for advanced esophageal cancer is a standard treatment alongside surgical treatment. Although numerous investigators have attempted to identify the predictive markers for chemoradiosensitivity, there appear to be few candidates that can be applied in clinical use. Using biopsy specimens, we investigated the apoptotic index (AI) prior to treatment and following a radiation dose of 10 Gy to detect the early response to chemoradiotherapy in 28 patients with esophageal squamous cell carcinoma. Molecular markers, including p53, p21, bax, bcl-2, HSP27, HSP70, HSP90, Ku70, Ku86 and HIF-1α, were also examined by immunohistochemical staining. The patients were divided into two groups depending on the response to chemoradiotherapy: a responder group (RG) (n=19) that included the patients with complete or partial response, and a non-responder group (NRG) (n=9), that included patients with stable or progressive disease. In the RG and NRG, the AI of pretreatment was 4.7±5.3 (mean ± SD, cells/1,000 cells) and 5.9±3.7, respectively. The apoptotic index ratio (AIR), which was determined by dividing the AI following 10 Gy radiation by the pretreatment AI, was higher in the RG compared to the NRG (4.7±4.5 versus 1.9±1.4, p=0.03). When the cut-off value of AIR was set at 2.4, the sensitivity, specificity and accuracy were 74, 78 and 76%, respectively. Among the molecular markers we examined immunohistochemically, a positive p53 expression in the pretreatment evaluation was associated with the efficacy of chemoradiotherapy (p=0.08). Regarding the expression of other molecular markers, no significant correlations were found in RG and NRG. In the present study, the results indicated that AIR is useful for the prediction of chemoradiosensitivity in esophageal squamous cell carcinoma.
晚期食管癌的放化疗是与手术治疗并列的标准治疗方法。尽管众多研究人员试图确定放化疗敏感性的预测标志物,但似乎几乎没有可应用于临床的候选标志物。我们使用活检标本,对28例食管鳞状细胞癌患者在治疗前以及给予10 Gy辐射剂量后进行凋亡指数(AI)检测,以检测放化疗的早期反应。还通过免疫组织化学染色检查了包括p53、p21、bax、bcl-2、HSP27、HSP70、HSP90、Ku70、Ku86和HIF-1α在内的分子标志物。根据对放化疗的反应将患者分为两组:反应组(RG)(n = 19),包括完全或部分缓解的患者;无反应组(NRG)(n = 9),包括病情稳定或进展的患者。在RG组和NRG组中,治疗前的AI分别为4.7±5.3(平均值±标准差,细胞/1000个细胞)和5.9±3.7。凋亡指数比(AIR)通过将10 Gy辐射后的AI除以治疗前的AI来确定,RG组的AIR高于NRG组(4.7±4.5对1.9±1.4,p = 0.03)。当AIR的临界值设定为2.4时,敏感性、特异性和准确性分别为74%、78%和76%。在我们通过免疫组织化学检查的分子标志物中,治疗前评估中p53的阳性表达与放化疗疗效相关(p = 0.08)。关于其他分子标志物的表达,在RG组和NRG组中未发现显著相关性。在本研究中,结果表明AIR可用于预测食管鳞状细胞癌的放化疗敏感性。