Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical Sciences, Kagoshima University, Kagoshima, Japan.
Ann Surg Oncol. 2018 Feb;25(2):449-455. doi: 10.1245/s10434-017-6271-y. Epub 2017 Nov 29.
While chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC), it is important to predict response prior to treatment by using markers because some patients respond well and others do not.
Fifty-nine patients with ESCC were treated with neoadjuvant CRT at the Kagoshima University Hospital. The expression of seven types of biomarker candidate proteins in biopsy specimens of untreated primary tumors was evaluated to determine whether it correlated with response and prognosis.
The positive expression rates were 47% for p53, 83% for CDC25B, 68% for 14-3-3sigma, 76% for p53R2, 75% for ERCC1, 32% for Gli-1, and 54% for Nrf2. In terms of histological response, tumor grade of the 59 patients was 48.8% for grade 1 as the non-responder, 29.2% for grade 2, and 22.0% for grade 3 as the responder. CRT was significantly effective in p53(-), p53R2(-), ERCC1(-), and Nrf2(-) tumors, while p53(-), p53R2(-), and ERCC1(-) were factors independently correlated with effective histological response. Their combined expression of two or three negative expressions had 100% effective response and was a significant prognostic factor.
Our results suggest that two or three negative expressions of p53, p53R2, and ERCC1 in biopsy specimens of primary tumors were associated with a favorable response to CRT for ESCC. Assessment of tumor suppressor and DNA repair protein expressions in biopsy specimens may be useful for the potential utility of CRT therapy for patients with ESCC prior to treatment.
放化疗(CRT)是治疗食管鳞癌(ESCC)最有效的方法之一,但由于并非所有患者均对治疗有反应,因此在治疗前使用标志物预测反应很重要。
在鹿儿岛大学医院,59 例 ESCC 患者接受了新辅助 CRT 治疗。评估未经治疗的原发肿瘤活检标本中七种生物标志物候选蛋白的表达情况,以确定其是否与反应和预后相关。
p53、CDC25B、14-3-3sigma、p53R2、ERCC1、Gli-1 和 Nrf2 的阳性表达率分别为 47%、83%、68%、76%、75%、32%和 54%。就组织学反应而言,59 例患者的肿瘤分级为 48.8%的 1 级为无反应者,29.2%的 2 级和 22.0%的 3 级为反应者。p53(-)、p53R2(-)、ERCC1(-)和 Nrf2(-)肿瘤对 CRT 有明显疗效,而 p53(-)、p53R2(-)和 ERCC1(-)是与有效组织学反应相关的独立因素。它们的两个或三个阴性表达的联合表达具有 100%的有效反应,是一个显著的预后因素。
我们的结果表明,原发肿瘤活检标本中 p53、p53R2 和 ERCC1 的两个或三个阴性表达与 ESCC 对 CRT 的良好反应相关。评估肿瘤抑制蛋白和 DNA 修复蛋白在活检标本中的表达可能有助于预测 ESCC 患者 CRT 治疗的潜在疗效。