Wagner Patrick L, Hyjek Elizabeth, Vazquez Madeline F, Meherally Danish, Liu Yi Fang, Chadwick Paul A, Rengifo Tatiana, Sica Gabriel L, Port Jeffrey L, Lee Paul C, Paul Subroto, Altorki Nasser K, Saqi Anjali
Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10021, USA.
J Thorac Cardiovasc Surg. 2009 Mar;137(3):615-21. doi: 10.1016/j.jtcvs.2008.07.039. Epub 2008 Sep 19.
Although the chemokine CXCL12 and its receptor CXCR4 have been implicated in metastasis of non-small cell lung carcinoma, the prognostic significance of these molecules is poorly defined. This study aimed to determine whether expression of these molecules is associated with clinicopathologic features and disease-free survival in non-small cell lung carcinoma.
Immunohistochemical staining for CXCL12 and CXCR4 was performed on 154 primary non-small cell lung carcinomas. Staining intensity was compared with tumor histotype, TNM stage, and disease-free survival; correlation was assessed by using the Fisher's exact test, and Kaplan-Meier and Cox multivariate proportional hazards regression analysis.
Intense CXCL12 immunostaining was associated with nodal metastasis, although no difference in survival was observed. The prognostic relevance of CXCR4 was dependent on its subcellular location: in univariate analysis intense nuclear staining was significantly associated with lower T classification and improved disease-free survival in patients with adenocarcinoma, whereas cytomembranous staining was associated with distant metastasis and decreased disease-free survival. On multivariate analysis, cytomembranous CXCR4 expression conferred a significantly worse disease-free survival (relative risk, 2.8; 95% confidence interval, 1.4-5.7; P = .004).
Cytomembranous expression of the chemokine receptor CXCR4 in adenocarcinoma of the lung is an independent risk factor associated with worse disease-free survival, whereas nuclear staining confers a survival benefit. These findings are consistent with a model in which CXCR4 promotes tumor cell proliferation and metastasis when present in the cytoplasm or cell membrane, whereas localization of this molecule in the nucleus prevents it from exerting these effects.
尽管趋化因子CXCL12及其受体CXCR4与非小细胞肺癌转移有关，但这些分子的预后意义仍不明确。本研究旨在确定这些分子的表达是否与非小细胞肺癌的临床病理特征及无病生存期相关。
对154例原发性非小细胞肺癌进行CXCL12和CXCR4的免疫组化染色。将染色强度与肿瘤组织学类型、TNM分期及无病生存期进行比较；采用Fisher精确检验、Kaplan-Meier法及Cox多因素比例风险回归分析评估相关性。
CXCL12免疫染色强与淋巴结转移相关，但未观察到生存期差异。CXCR4的预后相关性取决于其亚细胞定位：单因素分析中，腺癌患者细胞核染色强与较低的T分级及较好的无病生存期显著相关，而细胞膜染色与远处转移及较差的无病生存期相关。多因素分析中，细胞膜CXCR4表达导致无病生存期显著更差（相对风险，2.8；95%可信区间，1.4 - 5.7；P = 0.004）。
肺腺癌中趋化因子受体CXCR4的细胞膜表达是与较差无病生存期相关的独立危险因素，而细胞核染色则带来生存获益。这些发现与一种模型相符，即当CXCR4存在于细胞质或细胞膜时促进肿瘤细胞增殖和转移，而该分子定位于细胞核则可阻止其发挥这些作用。
