Department of Pathology, Technical University of Munich, Munich, Germany.
Int J Colorectal Dis. 2010 Apr;25(4):515-21. doi: 10.1007/s00384-009-0867-z. Epub 2009 Dec 15.
Pretherapeutic identification of esophageal squamous cell carcinomas (ESCCs) that are likely to respond to neoadjuvant chemoradiotherapy is important in the attempt to improve the prognosis for patients. In the present study, expression of members of the transforming growth factor-beta1 (TGF-beta1) signaling pathway was investigated in pretherapeutic biopsies from 97 ESCCs (cT3, cN0/+, cM0) in patients who underwent neoadjuvant chemoradiotherapy (45 Gy plus cisplatin and 5-fluorouracil) and subsequent esophagectomy in the setting of a single-center prospective treatment trial.
Expression of TGF-beta1 and its downstream effectors Smad4 and Smad7 was assessed using quantitative reverse transcription polymerase chain reaction from RNA prepared from pretherapeutic tumor biopsies. The presence of phosphorylated Smad2 was assessed immunohistochemically.
Expression of TGF-beta1 (mean 7.8; range 0.0-25.7 arb. units), Smad4 (mean 0.1; range 0.0-0.4 arb. units), and Smad7 (mean 1.6; range 0.4-16.1 arb. units) varied substantially between the patients. Tumors with total or subtotal regression, as determined by histopathological examination after neoadjuvant chemoradiotherapy, showed significantly higher levels of Smad4 mRNA expression than tumors with minor or no regression (P = 0.032). TGF-beta1 and Smad7 mRNA expression as well as Smad2 protein expression were of no prognostic value. Expression of the four genes under analysis also showed no impact on the overall survival. In contrast, the overall survival correlated significantly with histopathological regression (P < 0.0001) and to a minor degree also with clinical regression grading (P = 0.0254).
Among the parameters analyzed, only Smad4 was found to have possible predictive value for esophageal squamous cell carcinoma in patients receiving neoadjuvant chemoradiotherapy.
在尝试改善患者预后的过程中，预测接受新辅助放化疗的食管鳞癌（ESCC）对治疗的反应非常重要。在本研究中，我们对 97 例接受新辅助放化疗（45Gy 联合顺铂和 5-氟尿嘧啶）和随后的食管切除术的 ESCC 患者（cT3、cN0/+、cM0）的治疗前活检进行了转化生长因子-β1（TGF-β1）信号通路成员的表达分析，这些患者来自一项单中心前瞻性治疗试验。
使用定量逆转录聚合酶链反应（qRT-PCR）从治疗前肿瘤活检的 RNA 中评估 TGF-β1 及其下游效应子 Smad4 和 Smad7 的表达。使用免疫组织化学方法评估磷酸化 Smad2 的存在。
TGF-β1（平均 7.8；范围 0.0-25.7 arb.单位）、Smad4（平均 0.1；范围 0.0-0.4 arb.单位）和 Smad7（平均 1.6；范围 0.4-16.1 arb.单位）在患者之间的表达差异很大。新辅助放化疗后组织病理学检查确定完全或部分消退的肿瘤的 Smad4 mRNA 表达水平明显高于部分或无消退的肿瘤（P=0.032）。TGF-β1 和 Smad7 mRNA 表达以及 Smad2 蛋白表达均无预后价值。分析的四个基因的表达也与总生存期无显著相关性。相反，总生存期与组织学消退显著相关（P<0.0001），与临床消退分级也有一定程度的相关（P=0.0254）。
在分析的参数中，只有 Smad4 被发现对接受新辅助放化疗的食管鳞癌患者具有潜在的预测价值。
