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指导食管胃交界部肿瘤淋巴结清扫范围的新证据:Ber-Ep4联合CD44v6染色在检测下纵隔淋巴结微转移中的应用及生存分析

New evidence guiding extent of lymphadenectomy for esophagogastric junction tumor: Application of Ber-Ep4 Joint with CD44v6 staining on the detection of lower mediastinal lymph node micrometastasis and survival analysis.

作者信息

Zheng Bin, Ni Chen-Hui, Chen Hao, Wu Wei-Dong, Guo Zhao-Hui, Zhu Yong, Zheng Wei, Chen Chun

机构信息

Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China.

出版信息

Medicine (Baltimore). 2017 Apr;96(14):e6533. doi: 10.1097/MD.0000000000006533.

DOI:10.1097/MD.0000000000006533
PMID:28383418
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5411202/
Abstract

For Siewert type II adenocarcinoma of the esophagogastric junction (AEJ), the optimal surgical approach and extent of lymph nodes dissection remain controversial. Immunohistochemistry (IHC) has been reported to be available for identifying lymph node micrometastasis (LNMM) in patients with AEJ. This was a prospective case series of patients who underwent R0 resection and lower mediastinal lymphadenectomy from January 2010 to June 2015 in Fujian Medical University Union Hospital for Siewert type II AEJ. The outcomes were analyzed retrospectively. A total of 1325 lymph nodes were collected from 49 patients, grouped into 3 groups: lower mediastinal, paracardial, and abdominal. The former 2 groups were examined by monoclonal antibodies against Ber-Ep4 and CD44v6. The incidence of LNMM in mediastinal group was 37% (18/49) for Ber-Ep4 and 33% (16/49) for CD44v6. While in routine histological diagnosis, the number of patients with the positive lymph nodes was 7 (14%). When combining IHC with histopathology (HE) staining, the incidence of positive mediastinal lymph nodes was increased to 24%, with a total number of 37 lymph nodes from 28 patients (57%). Micrometastases indicated by Ber-Ep4 and CD44v6 were associated with the depth of tumor invasion (P = 0.020 and 0.037, respectively), histopathological nodal status (P = 0.024 and 0.01, respectively), and Lauren classification (P = 0.038 and, respectively). Expression of CD44v6 and Ber-Ep4 was positively correlated (r = 0.643, P < 0.001). The 3- and 5-year survival rates for all patients were 66% and 50%, respectively. The patients with LNMM had a lower 3-year survival rate of 51%, compared to 80% from no LNMM group; 5-year survival rate was also lower in LNMM group, which is 29% versus 68% (P = 0.006) in the no LNMM group. Patients with positive Ber-Ep4 cells had a lower survival, but not statistically significant (P = 0.058). CD44v6-positive group had a significantly reduced survival (P < 0.001). In patients group with negative lower mediastinal lymph nodes, patients without LNMM obtained a significant survival benefit (P = 0.021). Our study demonstrated that routine test for LNMM is necessary for patients with negative lymph nodes. As a positive prognostic factor, thorough lower mediastinal lymphadenectomy in an invasive approach should be considered when necessary. Ber-Ep4 and CD44v6 were shown to be great markers for detecting LNMM.

摘要

对于食管胃交界部(AEJ)的Siewert II型腺癌,最佳手术方式及淋巴结清扫范围仍存在争议。据报道,免疫组织化学(IHC)可用于识别AEJ患者的淋巴结微转移(LNMM)。这是一项前瞻性病例系列研究,纳入了2010年1月至2015年6月在福建医科大学附属协和医院接受R0切除及下纵隔淋巴结清扫术的Siewert II型AEJ患者。对结果进行回顾性分析。共收集了49例患者的1325枚淋巴结,分为3组:下纵隔组、贲门旁组和腹部组。前两组采用抗Ber-Ep4和CD44v6单克隆抗体进行检测。纵隔组中,Ber-Ep4检测LNMM的发生率为37%(18/49),CD44v6为33%(16/49)。而在常规组织学诊断中,淋巴结阳性患者为7例(14%)。当IHC与组织病理学(HE)染色相结合时,纵隔淋巴结阳性发生率增至24%,28例患者共37枚淋巴结(57%)。Ber-Ep4和CD44v6所提示的微转移与肿瘤浸润深度(分别为P = 0.020和0.037)、组织病理学淋巴结状态(分别为P = 0.024和0.01)及Lauren分型(分别为P = 0.038)相关。CD44v6和Ber-Ep4的表达呈正相关(r = 0.643,P < 0.001)。所有患者的3年和5年生存率分别为66%和50%。有LNMM的患者3年生存率较低,为51%,而无LNMM组为80%;LNMM组的5年生存率也较低,分别为29%和68%(P = 0.006)。Ber-Ep4细胞阳性的患者生存率较低,但无统计学意义(P = 0.058)。CD44v6阳性组生存率显著降低(P < 0.001)。在下纵隔淋巴结阴性的患者组中,无LNMM的患者有显著的生存获益(P = 0.021)。我们的研究表明,对于淋巴结阴性的患者,常规检测LNMM是必要的。作为一个积极的预后因素,必要时应考虑采用侵入性方法进行彻底的下纵隔淋巴结清扫。Ber-Ep4和CD44v6被证明是检测LNMM的良好标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94ae/5411202/77fef3c3e3d6/medi-96-e6533-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94ae/5411202/77fef3c3e3d6/medi-96-e6533-g008.jpg

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