Holzer Timothy R, Fulford Angie D, Reising Leslie O'Neill, Nedderman Drew M, Zhang Xuekui, Benjamin Laura E, Schade Andrew E, Nasir Aejaz
Diagnostic and Experimental Pathology, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, U.S.A.
Oncology Statistics, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, U.S.A.
Anticancer Res. 2016 Jul;36(7):3277-88.
the vascular endothelial growth factor (VEGF) pathway plays a prominent role in the growth and progression of human cancer, including non-small cell lung carcinoma (NSCLC). The key mediators of VEGF signaling are a family of related receptor tyrosine kinases that include VEGFR1, VEGFR2, and VEGFR3. The relative expression levels, activity, and cross-talk among these receptors may contribute to response of NSCLC to anti-angiogenic therapies, and a better systematic, translatable approach to categorizing tumors is needed.
We comparatively evaluated immunohistochemical expression of the three VEGFRs in archival primary NSCLC tissues (n=96).
VEGFR1 and VEGFR2 were localized both in vessels and tumor cells, while VEGFR3 was only localized in tumor vessels. A set of eight VEGFR staining subclasses were identified: Triple VEGFR positive (n=11, 11.5%), VEGFR1 predominant (n=22, 22.9%), VEGFR2 predominant (n=9, 9.4%), VEGFR3 predominant (n=3, 3.1%), VEGFR1/2 predominant (13, 13.5%), VEGFR1/3 predominant (2, 2.1%), VEGFR2/3 predominant (n=8, 8.3%), and triple VEGFR negative (n=28, 29.2%). An objective categorization based on K-means clustering revealed four clusters, three of which showed high VEGFR2 compared to VEGFR3 (30.7% of cases), cases high in both VEGFR2 and VEGFR3 (18.2%), and cases that were negative/low for both VEGFR2 and VEGFR3 (45.4%). A positive association between VEGFR2 and VEGFR3 was found, however no associations were observed between VEGFR1 and VEGFR2, nor VEGFR1 and VEGFR3.
The proposed subclasses of NSCLC are an approach for complementing lines of investigation of anti-angiogenic therapies beginning with systematic characterization of the disease.
血管内皮生长因子（VEGF）通路在包括非小细胞肺癌（NSCLC）在内的人类癌症的生长和进展中起着重要作用。VEGF信号传导的关键介质是一组相关的受体酪氨酸激酶家族，包括VEGFR1、VEGFR2和VEGFR3。这些受体之间的相对表达水平、活性和相互作用可能有助于NSCLC对抗血管生成疗法的反应，因此需要一种更好的系统的、可转化的方法来对肿瘤进行分类。
我们比较评估了存档的原发性NSCLC组织（n = 96）中三种VEGFR的免疫组化表达。
VEGFR1和VEGFR2定位于血管和肿瘤细胞中，而VEGFR3仅定位于肿瘤血管中。确定了一组八个VEGFR染色亚类：三重VEGFR阳性（n = 11，11.5%）、VEGFR1占主导（n = 22，22.9%）、VEGFR2占主导（n = 9，9.4%）、VEGFR3占主导（n = 3，3.1%）、VEGFR1/2占主导（13，13.5%）、VEGFR1/3占主导（2，2.1%）、VEGFR2/3占主导（n = 8，8.3%）和三重VEGFR阴性（n = 28，29.2%）。基于K均值聚类的客观分类揭示了四个聚类，其中三个聚类显示VEGFR2相对于VEGFR3较高（30.7%的病例）、VEGFR2和VEGFR3均高的病例（18.2%）以及VEGFR2和VEGFR3均为阴性/低表达的病例（45.4%）。发现VEGFR2和VEGFR3之间存在正相关，然而未观察到VEGFR1与VEGFR2之间以及VEGFR1与VEGFR3之间存在关联。
所提出的NSCLC亚类是一种从疾病的系统特征开始补充抗血管生成疗法研究方向的方法。
