p53 蛋白表达异常与 Barrett 食管患者肿瘤进展风险增加相关。
Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus.
机构信息
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, , Rotterdam, The Netherlands.
出版信息
Gut. 2013 Dec;62(12):1676-83. doi: 10.1136/gutjnl-2012-303594. Epub 2012 Dec 20.
OBJECTIVE
The value of surveillance for patients with Barrett's oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of discriminative tests for risk stratification. Histological diagnosis of low-grade dysplasia (LGD) is the only accepted predictor for progression to date, but has a low predictive value. The aim of this study was therefore to evaluate the value of p53 immunohistochemistry for predicting neoplastic progression in patients with BO.
DESIGN
We conducted a case-control study within a prospective cohort of 720 patients with BO. Patients who developed high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) were classified as cases and patients without neoplastic progression were classified as controls. P53 protein expression was determined by immunohistochemistry in more than 12 000 biopsies from 635 patients and was scored independently by two expert pathologists who were blinded to long-term outcome.
RESULTS
During follow-up, 49 (8%) patients developed HGD or OAC. P53 overexpression was associated with an increased risk of neoplastic progression in patients with BO after adjusting for age, gender, Barrett length and oesophagitis (adjusted relative risks (RR(a)) 5.6; 95% CI 3.1 to 10.3), but the risk was even higher with loss of p53 expression (RR(a) 14.0; 95% CI 5.3 to 37.2). The positive predictive value for neoplastic progression increased from 15% with histological diagnosis of LGD to 33% with LGD and concurrent aberrant p53 expression.
CONCLUSIONS
Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with BO and appears to be a more powerful predictor of neoplastic progression than histological diagnosis of LGD.
目的
鉴于肿瘤进展的总体发生率较低,且缺乏用于风险分层的鉴别性检测手段,针对巴雷特食管(BO)患者进行监测的价值目前仍存在争议。到目前为止,组织学诊断为低级别异型增生(LGD)是唯一被接受的进展预测指标,但预测价值较低。因此,本研究旨在评估 p53 免疫组化在预测 BO 患者肿瘤进展中的价值。
设计
我们在一个前瞻性队列的 720 例 BO 患者中开展了一项病例对照研究。将发生高级别异型增生(HGD)或食管腺癌(OAC)的患者归类为病例,无肿瘤进展的患者归类为对照。对 635 例患者的 12000 多个活检样本进行了 p53 蛋白表达的免疫组化检测,两位经验丰富的病理学家独立进行评分,他们对长期结局不知情。
结果
在随访期间,有 49(8%)例患者发生了 HGD 或 OAC。调整年龄、性别、BO 长度和食管炎后,p53 过表达与 BO 患者的肿瘤进展风险增加相关(校正后的相对风险(RR(a))5.6;95%CI 3.1 至 10.3),但 p53 表达缺失的风险更高(RR(a) 14.0;95%CI 5.3 至 37.2)。与单独的 LGD 组织学诊断相比,LGD 并伴有异常 p53 表达时,肿瘤进展的阳性预测值从 15%增加至 33%。
结论
异常的 p53 蛋白表达与 BO 患者的肿瘤进展风险增加相关,并且似乎是比 LGD 组织学诊断更有力的肿瘤进展预测指标。