Canine mammary carcinomas: influence of histological grade, vascular invasion, proliferation, microvessel density andVEGFR2expression on lymph node status and survival time

Abstract

Spontaneous invasive non-inflammatory canine mammary carcinomas (CMC) and their regional lymph nodes (LN) were analysed (n = 136). Histological grade (HG) and vascular invasion (VI) in the tumours and lymph node status were recorded. Proliferation index (PI), microvessel density (MVD) and vascular endothelial growth factor receptor 2 (VEGFR2) expression were estimated using anti-proliferating cell nuclear antigen (PCNA), anti-von Willebrand factor and anti-Flk-1, respectively. Eighteen months follow-up was performed (34 bitches). Tumours of different grades showed differences regarding PI, Flk-1/integrated optical density (Flk-1/IOD) and MVD. Every feature showed significant association with LN status through bivariate analyses. From multivariate analyses, VI and Flk-1/IOD were selected to predict LN status. Data revealed that the probability of a CMC-bearing bitch to remain alive at 1, 4, 5 and 14-18 months was 0.91, 0.87, 0.81 and 0.77, respectively. Besides LN status, VI was the only feature positively correlated with survival time, although a trend to shorter survival of animal patients bearing high expressing VEGFR2 CMC was noted.

Pilot assessment of vascular endothelial growth factor receptors and trafficking pathways in recurrent and metastatic canine subcutaneous mast cell tumours

“…Neoplastic cells from a variety of cancer types use VEGFR2 as an autocrine growth factor, and may employ a similar process to that observed in endothelial cells (von Marschall et al 2000;Strizzi et al 2001;Sher et al 2009;Adamcic et al 2012;Darrington et al 2012). Levels of neoplastic cell VEGFR2 expression were positively associated with lymph node status and a trend towards shorter survival time in canine mammary carcinoma (Diessler et al 2016). Here, we found a significant positive correlation between neoplastic cell expression of VEGFR2 and of pVEGFR2.…”

“…Levels of neoplastic cell VEGFR2 expression were positively associated with lymph node status and a trend towards shorter survival time in canine mammary carcinoma (Diessler et al . ). Here, we found a significant positive correlation between neoplastic cell expression of VEGFR2 and of pVEGFR2.…”

Canine invasive mammary carcinomas as models of human breast cancer. Part 1: natural history and prognostic factors

“…There was, however, a relative uncertainty of predictability of this spontaneous cancer as a translational model, as the natural history and prognostic factors have been described in relatively small cohorts [ 19 – 25 , 27 – 41 ]. The present study is of particular interest because (1) mammary carcinomas in situ have been carefully excluded from analysis, using p63 immunohistochemistry when necessary, which is rarely, if ever, performed in veterinary studies, but of paramount importance in human breast oncology; (2) the cases were reviewed blindly by veterinary and medical pathologists, until consensus diagnoses were achieved, which permitted interpretation of canine samples using the criteria used for human breast cancer; (3) this is the largest cohort of CMCs described so far, which allowed for multivariate survival analyses with sufficient statistical power; (4) this study is one of the rare reports [ 14 , 15 , 17 , 30 , 37 ] of locoregional recurrence, distant metastasis-free interval, and specific survival in dogs with CMCs, as most previous studies focused on disease-free survival and overall survival only [ 18 – 21 , 23 – 25 , 28 , 29 , 31 , 32 , 35 , 38 , 39 ].…”

Assessment of postoperative adjuvant treatment using toceranib phosphate against adenocarcinoma in dogs

“…The membranes were incubated for 1 hour at room temperature in a blocking solution: 10 mM Tris‐HCl (pH 7.4), 0.15 M NaCl, 0.1% Tween 20, 1% BSA, and 0.05% NaN 3 . The membranes then were incubated overnight at 4°C with the primary antibodies, including anti‐β‐actin mouse monoclonal antibody (G043; Abcam, Cambridge, Massachusetts) and anti‐mouse VEGFR2 (Flk‐1‐A/3‐: sc‐6251, Santa Cruz Biotechnology Inc, Santa Cruz, California), and diluted 1 : 100 in phosphate‐buffered saline (PBS) 18 . The membranes then were washed 3 times for 5 minutes with Tween‐Tris‐buffered saline (TBS; 10 mM Tris‐HCl, 0.15 M NaCl, and 0.1% Tween 20), and then incubated with a horseradish‐peroxidase‐conjugated anti‐rabbit‐IgG secondary antibody (Fischer Scientific Thermo, Pittsburgh, Pennsylvania) in Tween‐TBS for 1 hour at room temperature.…”