Abstract 3004: VEGFR2 expression and vascular phenotyping demonstrate different patterns of tumor angiogenesis in human gastric and breast cancers
Authors: Holzer Timothy R. , Falcon Beverly L. , Fulford Angie D. , McDonald Sook A. , Ray Andy L. , Finnegan Patrick , Uhlik Mark T. , Benjamin Laura E. , Schade Andrew E. , Nasir Aejaz 
Published: May 2015

Abstract
Although some human gastric carcinomas (GCs) can have prominent tumor stroma, abundant desmoplastic tumor stroma is more typical of human invasive breast carcinomas (IBCs). Based on these pathologic differences, we hypothesized that these cancers may also have different tumor angiogenic response and tumor vascular phenotypes. We used a reference CD34 IHC assay and a novel VEGFR2 IHC assay to stain sections from customized human gastric (n=38) and breast (n=40) cancer tissue microarrays (TMAs). The absolute numbers of discrete VEGFR2+ and CD34+ tumor vessels were quantified in each TMA core. We also normalized the absolute VEGFR2 positive tumor vessel counts with the corresponding CD34-positive vessel counts, as VEGFR2 vascular positivity index (VEGFR2-VPI). Any case with &lt;50% tissue in TMA core, no invasive carcinoma tissue or any technical issue with accurate vascular vessel counts was excluded. Gastric adenocarcinomas (38 evaluable cores; 33 intestinal type, 4 diffuse, 1 mucinous): mean patient age was 58.4 years (range 35-81), mean VEGFR2 and CD34+ vascular counts were 42 (0-145) and 109 (11-216) respectively, and mean VEGFR2-vascular positivity index was 41 (0-97). Invasive breast carcinomas (40 evaluable cores; 33 invasive ductal, 7 invasive lobular): mean patient age was 67.9 years (40-76), mean VEGFR2 and CD34+ vascular counts were 20 (0-81) and 58 (8-162) respectively, and mean VEGFR2-vascular positivity index was 39 (0-97). Invasive ductal carcinomas: mean VEGFR2 and CD34+ vascular counts were 21 (3-81) and 55 (8-152) respectively, and mean VEGFR2-vascular positivity index was 41 (7-97). Invasive lobular carcinomas: mean VEGFR2 and CD34+ vascular counts were 17 (0-33) and 74 (39-162) respectively, and mean VEGFR2-vascular positivity index was 31 (0-62). Based on quantitative analysis of CD31+ and CD34+ tumor blood vessels on a fluorescence-based platform (iCys), we found more immature vascular phenotypes in human GCs, while many tumor blood vessels in IBCs exhibited a more mature vascular phenotype. Using a vascular contouring analyses, we found higher CD31+, CD34+ vascular counts and higher CD34/CD31 ratio in GCs compared to IBCs. Overall, human gastric carcinomas show more pronounced tumor angiogenesis than invasive breast carcinomas. Although we found more tumor blood vessels expressing VEGFR2 in gastric than breast cancer tissues, the ratio of VEGFR2 vessels normalized with CD34+ vascular counts were comparable. However, based on CD34 staining, gastric cancer tissues showed more of an immature vascular phenotype, as compared to breast cancer tissues which contained more mature vascular phenotypes. These findings merit further validation in independent cohorts.
Citation Format: Timothy R. Holzer, Beverly L. Falcon, Angie D. Fulford, Sook A. McDonald, Andy L. Ray, Patrick Finnegan, Mark T. Uhlik, Laura E. Benjamin, Andrew E. Schade, Aejaz Nasir. VEGFR2 expression and vascular phenotyping demonstrate different patterns of tumor angiogenesis in human gastric and breast cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3004. doi:10.1158/1538-7445.AM2014-3004