Warnecke-Eberz Ute, Hokita Shuichi, Xi Huan, Higashi Hiroshi, Baldus Stephan E, Metzger Ralf, Brabender Jan, Bollschweiler Elfriede, Mueller Rolf P, Dienes Hans P, Hoelscher Arnulf H, Schneider Paul M
Department of Visceral and Vascular Surgery, University of Cologne, Joseph-Stelzmann-Strasse 9, 50931 Cologne, Germany.
Oncol Rep. 2005 Jun;13(6):1241-6.
Survivin is a member of the inhibitor of apoptosis (IAP) gene family known to be involved in resistance to chemo- and radiation therapy. We examined the potential of quantitative survivin mRNA expression to predict histopathologic tumor response and prognosis following neoadjuvant radiochemotherapy (cis-platinum, 5-FU, 36 Gy) in patients with locally-advanced esophageal cancer (cT2-4, Nx, M0). Tumor (T) and normal tissue (N) samples from 51 patients were collected by endoscopic biopsy prior to treatment. Survivin mRNA expression was analyzed by quantitative real-time RT-PCR assays. Histomorphologic regression was defined as a major response when resected specimens contained <10% of residual vital tumor cells or if a pathologically complete response was achieved. Some 7/51 patients had progressive disease and 44/51 proceeded to surgical resection. Of 44 resected tumors, 17 (31.4%) showed a major and 27 (61.4%) showed a minor histopathologic response; the survival rates were significantly different (p<0.01). Median absolute survivin expression was 5.1 in the tumor and 2.4 in corresponding normal tissue samples (Wilcoxon, p<0.001). Median relative (T/N ratio) survivin mRNA expression was 1.7. Survivin mRNA expression levels did not show a significant association with histomorphologic regression. Relative survivin mRNA expression of a T/N ratio >1 indicated a favorable prognosis (log-rank, p<0.003). Expression levels of survivin mRNA in pretherapeutic biopsies did not predict the extent of histomorphologic tumor regression following preoperative radiochemotherapy for esophageal cancer. However, overexpression of survivin mRNA in pretreatment biopsies (T/N ratio >1) was associated with superior survival probabilities.
生存素是凋亡抑制蛋白（IAP）基因家族的成员，已知其与化疗和放疗耐药有关。我们研究了定量生存素mRNA表达预测局部晚期食管癌（cT2 - 4，Nx，M0）患者新辅助放化疗（顺铂、5 - 氟尿嘧啶、36 Gy）后组织病理学肿瘤反应和预后的潜力。在治疗前通过内镜活检收集了51例患者的肿瘤（T）和正常组织（N）样本。通过定量实时逆转录聚合酶链反应分析生存素mRNA表达。当切除标本中残留的存活肿瘤细胞<10%或实现病理完全缓解时，组织形态学消退被定义为主要反应。约7/51例患者疾病进展，44/51例患者进行了手术切除。在44例切除的肿瘤中，17例（31.4%）显示主要组织病理学反应，27例（61.4%）显示次要组织病理学反应；生存率有显著差异（p<0.01）。肿瘤中生存素的中位绝对表达为5.1，相应正常组织样本中为2.4（Wilcoxon检验，p<0.001）。生存素mRNA的中位相对（T/N比值）表达为1.7。生存素mRNA表达水平与组织形态学消退无显著相关性。T/N比值>1的生存素mRNA相对表达提示预后良好（对数秩检验，p<0.003）。治疗前活检中生存素mRNA的表达水平不能预测食管癌术前放化疗后组织形态学肿瘤消退的程度。然而，治疗前活检中生存素mRNA的过表达（T/N比值>1）与较高的生存概率相关。
