Hiroishi Kazuaki, Inomata Masafumi, Kashima Kenji, Yasuda Kazuhiro, Shiraishi Norio, Yokoyama Shigeo, Kitano Seigo
Departments of Surgery I and.
Exp Ther Med. 2011 May;2(3):465-470. doi: 10.3892/etm.2011.243. Epub 2011 Mar 21.
Pre-operative chemoradiotherapy (CRT) is an important neoadjuvant therapy for locally advanced rectal cancer. In the present study, we investigated the factors that influence the efficacy of pre-operative CRT in locally advanced rectal cancer. We divided 50 patients with locally advanced rectal carcinoma treated with pre-operative CRT into two groups according to the grade of tumor response to pre-operative CRT: low-sensitivity group and high-sensitivity group. As candidates for the prediction of sensitivity to pre-operative CRT, clinicopathological factors and 12 biomarkers, including factors related to tumor growth, cell cycle, apoptosis, tumor stroma and cancer stem cells, were examined immunohistochemically in 48 resected specimens. Thirty-one tumors showed high sensitivity and 19 showed low sensitivity to pre-operative CRT. The status of stem cell-related factors, CD133 and CD24, was significantly associated respectively with sensitivity to pre-operative CRT (P=0.003, P=0.029). In 10 tumors positive for both CD133 and CD24, low sensitivity to CRT was found in 9 (90%), whereas in 16 tumors negative for both CD133 and CD24, low sensitivity was found in 3 (19%). Other pathological parameters were not associated with tumor response to pre-operative CRT. In conclusion, overexpression of cancer stem cell-related factors, CD133 and CD24, is associated with the sensitivity of locally advanced rectal cancer to pre-operative CRT.
术前放化疗(CRT)是局部晚期直肠癌的一种重要新辅助治疗方法。在本研究中,我们调查了影响局部晚期直肠癌术前CRT疗效的因素。我们将50例接受术前CRT治疗的局部晚期直肠癌患者,根据术前CRT的肿瘤反应分级分为两组:低敏感组和高敏感组。作为预测术前CRT敏感性的候选因素,对48例切除标本进行免疫组化检测了临床病理因素和12种生物标志物,包括与肿瘤生长、细胞周期、凋亡、肿瘤基质和癌症干细胞相关的因素。31例肿瘤对术前CRT表现为高敏感,19例表现为低敏感。干细胞相关因子CD133和CD24的状态分别与术前CRT的敏感性显著相关(P = 0.003,P = 0.029)。在10例CD133和CD24均阳性的肿瘤中,9例(90%)对CRT低敏感,而在16例CD133和CD24均阴性的肿瘤中,3例(19%)对CRT低敏感。其他病理参数与术前CRT的肿瘤反应无关。总之,癌症干细胞相关因子CD133和CD24的过表达与局部晚期直肠癌对术前CRT的敏感性相关。