Immunohistochemical Expression of Angiogenic Factors by Neoplastic Epithelial Cells Is Associated With Canine Prostatic Carcinogenesis

Abstract

The dog is the only species, other than humans, in which spontaneous prostatic cancer occurs; therefore, dogs are a valuable model for the study of factors that regulate tumor progression. Angiogenesis is important in the development and spread of a variety of cancers, including prostate cancer. To better define the role of cancer epithelial cells in prostate cancer neovascularization, immunohistochemical staining for angiogenic factors (vascular endothelial growth factor [VEGF], platelet endothelial cell adhesion molecule-1 [PECAM-1], Tie-2, and fibroblast growth factor-2 [FGF-2]) was performed on formalin-fixed, paraffinembedded tissues from 10 normal prostates, 15 hyperplastic prostates, and 11 prostatic carcinomas from dogs. Normal and hyperplastic epithelial cells were negative for PECAM-1, VEGF, and Tie-2, while the same markers were expressed with a variable intensity of cytoplasmic staining by neoplastic cells. Mild to moderate FGF-2 staining was detected in all normal prostates with less than 10% of positive cells, mainly distributed in the basal layer. The percentage of FGF-2-positive hyperplastic cells was variable, with both basal and secretory cells exhibiting a perinuclear to diffuse cytoplasmic staining. The mean number of positive cells and the intensity of staining were higher in prostatic carcinomas than normal and hyperplastic prostates. Moreover, microvessel density analyzed on PECAM-1-stained slides was increased in prostate cancer compared with normal and hyperplastic prostates. Therefore, prostatic neoplastic cells are capable of simultaneous expression of various angiogenic factors and may increase tumor proliferation and angiogenesis in a paracrine and autocrine fashion.Keywords angiogenesis, carcinoma, dog, hyperplasia, immunohistochemistry, prostate Prostate cancer is the second leading cause of cancer-related death after lung cancer in men, and its incidence is steadily increasing in almost all countries.9 Prostate cancer progression occurs in 2 stages, the first being androgen responsive and the second androgen independent with a high metastatic rate.

Seasonal expressions of VEGF and its receptors VEGFR1 and VEGFR2 in the prostate of the wild ground squirrels (<em>Spermophilus dauricus</em>)

“…35 In the present study, VEGF, VEGFR1 and VEGFR2 were presented in epithelial and stromal cells during both the breeding and non-breeding seasons, which suggested that the prostate of the wild male ground squirrels potentially possessed the ability to synthesize VEGF and its receptors, and it was concluded that VEGF might affect the physiological functions of the prostate. Similar results also were observed in other breeding mammals, including human, 36 mice 37 and dogs, 38 which showed that VEGF and its receptors regulated a series of physiological responses, such as proliferation and migration of prostatic endothelial cells and vascular permeability, in the form of paracrine or autocrine. Our previous studies showed that COX-1, COX-2, prostaglandin E synthase (PTGES) and prostaglandins E2 receptors (PTGERs) were expressed in the epithelial and stromal cells of the prostate during the breeding and non-breeding seasons, thus suggesting that PGE2 synthesis and signaling might play an important autocrine or paracrine role in the regulation of seasonal changes in the prostatic function of the wild ground squirrels.…”

Outcome and prognostic factors in medically treated canine prostatic carcinomas: A multi‐institutional study

“…Expression of angiogenic factors such as vascular endothelial growth factor has been detected in dogs with PC . While numbers in this study were too small and combination therapy with NSAIDs was used, drugs targeting these receptors may be a strategy for therapy in future research . Other potential targets could be the BRAF V595E mutation .…”

“…43 While numbers in this study were too small and combination therapy with NSAIDs was used, drugs targeting these receptors may be a strategy for therapy in future research. 44 Other potential targets could be the BRAF V595E mutation. 18 Ten more dogs treated with metronomic chemotherapy plus NSAIDs were assessed together with those patients receiving toceranib phosphate as a separate group and compared to dogs treated with NSAIDs alone.…”

Tyrosine Kinase Receptor Expression in Canine Liposarcoma

“…Most LPs examined were characterized by high FGF2 expression, chiefly in well-differentiated and pleomorphic LP histotypes. FGF2 expression has been reported in several canine neoplasms, including epithelial tumors such as prostatic carcinoma, 41 endocrine and thyroid carcinoma, 43 and mesenchymal neoplasms such as hemangiosarcoma 55 and fibrosarcoma. 14 FGF2 expression has also been investigated in human STS where FGF2 plasma levels were higher than in healthy controls.…”