期刊
CANCER CELL INTERNATIONAL
卷 17, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s12935-017-0427-5
关键词
Breast cancer; HER2; Angiogenesis; VEGFR2; Ramucirumab; Antiangiogenic therapy
类别
资金
- Eli Lilly and Company, USA
Background: Clinically relevant predictive biomarkers to tailor anti-angiogenic therapies to breast cancer (BRC) patient subpopulations are an unmet need. Methods: 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. Results: 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). Conclusion: 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.
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