细胞质E-钙黏蛋白表达与转移性结直肠癌患者较高的VEGFA肿瘤水平、基于伊立替康治疗的较低缓解率及较差预后相关。

Cytoplasmic E-Cadherin Expression Is Associated With Higher Tumour Level of VEGFA, Lower Response Rate to Irinotecan-based Treatment and Poorer Prognosis in Patients With Metastatic Colorectal Cancer.

作者信息

Bendardaf Riyad, Sharif-Askari Fatemeh Saheb, Sharif-Askari Narjes Saheb, Syrjänen Kari, Pyrhönen Seppo

机构信息

Oncology Unit, University Hospital Sharjah, Sharjah, United Arab Emirates.

Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.

出版信息

Anticancer Res. 2019 Apr;39(4):1953-1957. doi: 10.21873/anticanres.13305.

DOI:10.21873/anticanres.13305

PMID:30952738

Abstract

BACKGROUND

The prognostic value of vascular endothelial growth factor-A (VEGFA) and epithelial cadherin (E-cadherin) expression in patients with metastatic colorectal cancer (mCRC) is controversial.

MATERIALS AND METHODS

In this prospective study, patients diagnosed with mCRC between August 1, 1998, and August 30, 2003, at the Turku University Hospital, Finland were included. Expression of E-cadherin (membranous and cytoplasmic pattern) and VEGFA in tumour samples was assessed by immunohistochemistry. Tumours were classified as E-cadherin expressers if they demonstrated moderate or strong cytoplasmic or membranous staining, while those positive for VEGFA expression showed a moderate or strong cytoplasmic staining. Of particular interest was the association between membranous or cytoplasmic expression of E-cadherin and VEGFA. The value of strong VEGF-A staining and membranous or cytoplasmic expression of E-cadherin as a predictor of disease outcome over a 6-year period was another point of interest in this study.

RESULTS

Of the 67 patients with mCRC, 43 (64%) had tumours positive for cytoplasmic E-cadherin, while in 24 cases (36%), E-cadherin expression was membranous. Strong VEGFA staining was present in half of the cases (n=36, 54% of all 67 mCRC cases). VEGFA expression was significantly correlated with cytoplasmic E-cadherin expression in that 28/36 cases of VEGFA-positive tumours were also positive for cytoplasmic E-cadherin (p=0.012). In addition, among the patients with intense VEGFA expression (n=36), those who had positive cytoplasmic E-cadherin in their tumours had a lower response-rate to first-line therapy with irinotecan, fluorouracil and leucovorin regimen: 5 out of 36 (14%) were chemosensitive. This is in contrast to the patients with VEGFA-positive tumours and membranous E-cadherin (8/36, 22% chemosensitive (p=0.004). The former group also had more ominous prognosis (p<0.001).

CONCLUSION

Reduced membranous expression of E-cadherin and increased cytoplasmic E-cadherin expression predict poor survival in mCRC.

摘要

背景

血管内皮生长因子 -A（VEGFA）和上皮钙黏蛋白（E - cadherin）表达在转移性结直肠癌（mCRC）患者中的预后价值存在争议。

材料与方法

在这项前瞻性研究中，纳入了1998年8月1日至2003年8月30日期间在芬兰图尔库大学医院被诊断为mCRC的患者。通过免疫组织化学评估肿瘤样本中E - cadherin（膜性和细胞质模式）和VEGFA的表达。如果肿瘤表现出中度或强细胞质或膜性染色，则将其分类为E - cadherin表达者，而VEGFA表达阳性者表现为中度或强细胞质染色。特别感兴趣的是E - cadherin的膜性或细胞质表达与VEGFA之间的关联。在本研究中，另一个感兴趣的点是强VEGF - A染色以及E - cadherin的膜性或细胞质表达作为6年疾病结局预测指标的价值。

结果

在67例mCRC患者中，43例（64%）肿瘤细胞质E - cadherin阳性，而24例（36%）E - cadherin表达为膜性。一半病例（n = 36，占所有67例mCRC病例的54%）存在强VEGFA染色。VEGFA表达与细胞质E - cadherin表达显著相关，因为36例VEGFA阳性肿瘤中有28例细胞质E - cadherin也呈阳性（p = = 0.012）。此外，在VEGFA高表达患者（n = 36）中，肿瘤细胞质E - cadherin阳性的患者对伊立替康、氟尿嘧啶和亚叶酸钙方案一线治疗的反应率较低：36例中有5例（14%）对化疗敏感。这与VEGFA阳性肿瘤且E - cadherin为膜性的患者形成对比（8/36，22%对化疗敏感，p = 0.004）。前一组的预后也更差（p < 0.001）。