Department of the School of Medicine, Yale University School of Medicine, New Haven, CT, USA.
J Transl Med. 2013 Jan 14;11:15. doi: 10.1186/1479-5876-11-15.
Anti-angiogenic therapies are among the most commonly used drugs in renal cell carcinoma. Tumor vascularity, defined by microvessel area, may be associated with response to these drugs. Clinical studies suggest that metastatic sites are more responsive than primary tumors. Our purpose was to characterize microvessel area (MVA) in matched primary and metastatic samples and in samples of different histologies.
We employed a method of automated, quantitative analysis of in situ tumor components to identify the area of CD-34 staining endothelial cells within renal cell carcinoma tumors. MVA was assessed in corresponding primary and metastatic samples from 34 patients, as well as in 334 primary nephrectomy specimens with variable histologies.
MVA measurements from different parts of the same tumor correlated well (R = 0.75), indicating that MVA was fairly uniform within a tumor. While MVA was slightly higher in primary tumors than corresponding metastatic sites, the difference was not statistically significant (P = 0.1). MVA in paired primary and metastatic samples correlated moderately well (R = 0.36). MVA was higher in clear cell than papillary histology and oncocytomas (P < 0.0001 and P = 0.018, respectively).
Lack of significant differences MVA in matched primary and metastatic samples suggests that both types of tumors should respond to anti-angiogenic drugs. This should be confirmed on additional cohorts. Given the small cohort, future predictive biomarker studies entailing MVA measurements should include specimens from both sites. Clear cell carcinomas are more vascular than other histologic subtypes, which may explain the higher response rates to anti-angiogenic therapies in clear cell tumors.
抗血管生成疗法是肾细胞癌中最常用的药物之一。肿瘤血管生成，由微血管面积定义，可能与这些药物的反应相关。临床研究表明，转移部位比原发性肿瘤更有反应。我们的目的是描述匹配的原发性和转移性样本以及不同组织学样本中的微血管面积（MVA）。
我们采用了一种自动、定量分析原位肿瘤成分的方法，以确定肾细胞癌肿瘤中 CD-34 染色内皮细胞的面积。在 34 名患者的相应原发性和转移性样本中以及 334 份具有不同组织学的原发性肾切除术标本中评估了 MVA。
同一肿瘤不同部位的 MVA 测量值相关性良好（R=0.75），表明 MVA 在肿瘤内相当均匀。虽然原发性肿瘤中的 MVA 略高于相应的转移性部位，但差异无统计学意义（P=0.1）。配对的原发性和转移性样本中的 MVA 中度相关（R=0.36）。透明细胞组织学和嗜酸细胞瘤的 MVA 高于乳头状组织学（P<0.0001 和 P=0.018）。
匹配的原发性和转移性样本中 MVA 无显著差异表明这两种类型的肿瘤都应该对抗血管生成药物有反应。这应该在其他队列中得到证实。鉴于小样本量，未来涉及 MVA 测量的预测生物标志物研究应包括来自两个部位的标本。透明细胞癌比其他组织学亚型更具血管生成性，这可能解释了抗血管生成治疗在透明细胞肿瘤中更高的反应率。
