Differential Expression Of Vegfr2 Protein In Her2 Positive Primary Human Breast Cancer: Potential Relevance To Newer Anti-Angiogenic Therapies

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PAPreviously, we demonstrated immunohistochemical expression of VEGFR2 protein and vascular phenotypes in human breast carcinomas (Holzer, Nasir et al AACR 2014). Here, we carried out a large-scale immunopathologic analysis of tumor vascular density and differential expression of VEGFR2 protein in various subsets of primary human breast carcinomas from 186 females (Mean age: 59 years; range 33-88 years). Sections from a primary breast cancer tissue microarray (Yale University), were stained for a sensitive tumor vascular marker (CD34) and for VEGFR2 protein using a novel VEGFR2 IHC assay developed and standardized in our laboratory (Holzer, Nasir et al PLOS One 2013). Discrete VEGFR2+ and CD34+ tumor vessels were counted in each analyzable TMA core by an experienced breast pathologist, excluding any suboptimal/inadequate cores or any areas of tumor necrosis. Histologic subtypes of primary breast carcinomas included invasive ductal, lobular, mixed ductal-lobular and colloid (N = 139, 22, 18, 7) respectively. Based on hormone receptor (HR) and Her2 status, cases were grouped into HR+, Her2+ and triple-negative subsets. Pathologic assessments of vascular density (CD34 counts) and imunohistochemical expression of VEGFR2 protein were made only in the viable invasive carcinoma tissue. The observed CD34+ and VEGFR2+ tumor vascular counts in individual cases were heterogeneous, ranging from high vascular density and high VEGFR2 expression to minimal vascular density and/or minimal or no VEGFR2 expression. Among all histologies, mean CD34+ and VEGFR2+ tumor vascular counts were 11 and 3.4 per tumor TMA core respectively. Eighty-nine of 186 (48%) cases had u003e10 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 to 5 VEGFR2+ tumor vessels/TMA core, while 42/169 (25%) cores had no VEGFR2+ tumor vessels. Thirteen of 169 (8%) cases also showed tumor cell (cytoplasmic and/or membrane) expression of VEGFR2 protein. 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 = 0.03) and TNBC (p = 0.01) tissues. Compared to Her2- cases, Her2+ breast cancers had higher VEGFR2+ tumor vessel counts (p = 0.006). These data provide insights about tumor vascular density and vascular VEGFR2 expression in primary human breast cancer subtypes, especially Her2 positive breast cancer, and offer a pathobiologic hypothesis for the patterns of clinical response of breast cancer patients to newer anti-angiogenic therapies.Citation Format: Aejaz Nasir, Timothy R. Holzer, Michael Man, Laura E. Benjamin, Allen S. Melemed, Andrerw E. Schade. Differential expression of VEGFR2 Protein in HER2 positive primary human breast cancer: Potential relevance to newer anti-angiogenic therapies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4161. doi:10.1158/1538-7445.AM2015-4161