Differential expression of VEGFR2 protein in HER2 positive primary human breast cancer: potential relevance to anti-angiogenic therapies.
Differential expression of VEGFR2 protein in HER2 positive primary human breast cancer: potential relevance to anti-angiogenic therapies.
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DOI：
10.1186/s12935-017-0427-5
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发表时间：
2017
影响因子：
5.8
通讯作者：
Schade AE
中科院分区：
文献类型：
--
作者：
Nasir A;Holzer TR;Chen M;Man MZ;Schade AE
用于针对乳腺癌（BRC）患者亚群定制抗血管生成疗法的临床相关预测生物标志物的需求尚未得到满足。我们使用组织微阵列分析了原代人类 BRC 的各个亚群（186 名女性；平均年龄：59 岁；范围 33-88 岁）中的肿瘤血管密度和 VEGFR2 蛋白表达。对侵入性导管、小叶、混合导管-小叶和胶体 (N = 139、22、18、7) BRC 核心中的离散 VEGFR2+ 和 CD34+ 肿瘤血管进行手动评分。在个别病例中观察到的 CD34+ 和 VEGFR2+ 肿瘤血管计数是异质的。每个肿瘤 TMA 核心的平均 CD34+ 和 VEGFR2+ 肿瘤血管计数分别为 11 和 3.4。 186 例病例中的 89 例 (48%) 具有 >10 个 CD34+ 肿瘤血管，而 97/186 (52%) 的每个 TMA 核心中具有较少的 CD34+ 肿瘤血管。在 VEGFR2 染色 TMA 的 169 个可分析核心中，90 个 (53%) 显示 1-5 个 VEGFR2+ 肿瘤血管/TMA 核心，而 42/169 (25%) 个核心没有可检测到的 VEGFR2+ 肿瘤血管。 169 例中有 13 例 (8%) 也显示肿瘤细胞（细胞质/膜）表达 VEGFR2。与其他乳腺癌亚型相比，三阴性乳腺癌 (TNBC) 的血管似乎较少（平均 VD = 9.8，范围 0-34）。总体而言，与 HR+ (p = 0.04) 和 TNBC (p = 0.02) 组织相比，HER2+ 组织中的 VEGFR2+ 肿瘤血管计数显着更高。与 HER2− 病例相比，HER2+ 乳腺癌具有更高的 VEGFR2+ 肿瘤血管计数 (p = 0.007)。 HER2+ 乳腺癌病理性血管生成的表征为未来研究针对这种临床侵袭性乳腺癌亚型的 VEGF/VEGFR2 轴靶向药物的临床活性提供了科学依据。
Clinically relevant predictive biomarkers to tailor anti-angiogenic therapies to breast cancer (BRC) patient subpopulations are an unmet need. We analyzed tumor vascular density and VEGFR2 protein expression in various subsets of primary human BRCs (186 females; Mean age: 59 years; range 33–88 years), using a tissue microarray. Discrete VEGFR2+ and CD34+ tumor vessels were manually scored in invasive ductal, lobular, mixed ductal-lobular and colloid (N = 139, 22, 18, 7) BRC cores. The observed CD34+ and VEGFR2+ tumor vascular counts in individual cases were heterogeneous. Mean CD34+ and VEGFR2+ tumor vessel counts were 11 and 3.4 per tumor TMA core respectively. Eighty-nine of 186 (48%) cases had >10 CD34+ tumor vessels, while 97/186 (52%) had fewer CD34+ vessels in each TMA core. Of 169 analyzable cores in the VEGFR2 stained TMA, 90 (53%) showed 1–5 VEGFR2+ tumor vessels/TMA core, while 42/169 (25%) cores had no detectable VEGFR2+ tumor vessels. Thirteen of 169 (8%) cases also showed tumor cell (cytoplasmic/membrane) expression of VEGFR2. Triple-negative breast cancers (TNBCs) appeared to be less vascular (Mean VD = 9.8, range 0–34) than other breast cancer subtypes. Overall, VEGFR2+ tumor vessel counts were significantly higher in HER2+ as compared to HR+ (p = 0.04) and TNBC (p = 0.02) tissues. Compared to HER2− cases, HER2+ breast cancers had higher VEGFR2+ tumor vessel counts (p = 0.007). Characterization of pathologic angiogenesis in HER2+ breast cancer provides scientific rationale for future investigation of clinical activity of agents targeting the VEGF/VEGFR2 axis in this clinically aggressive breast cancer subtype.