Canine classical seminoma: a specific malignant type with human classifications is highly correlated with tumor angiogenesis

Abstract

Background: Human seminoma is classified as classical seminoma (SE) and spermatocytic seminoma (SS). Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD) being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels.

Methods: Twenty-three cases of canine seminomas (2 intratubular, 9 diffuse, and 12 intratubular/diffuse seminomas showing both intratubular and diffuse patterns) were classified as SE or SS by immunohistochemistry (IHC) using monoclonal antibody against PLAP and by PAS stain. The histopathological data were then compared to see if there was a correlation with SE or SS. Angiogenesis of seminomas were evaluated by immunohistochemical assay using polyclonal antibody against Von Willebrand factor (vWF) and by calculating the means of MVD, vessels area and perimeters using computerized image analysis. Statistical Package for Social Sciences (SPSS) program was used for various statistical analyses.

Results: The numbers of PLAP+/PAS+ canine SEs were 8/23 (34.8%) and PLAP-/PAS- SSs were 15/23 (61.2%). All SE cases (8/8, 100%) were intratubular/diffuse types. SS types included 2 intratubular (2/15, 13.3%), 9 diffuse (9/15, 60%), and 4 intratubular/diffuse (4/15, 26.7%) types. MVD and vascular parameters in SEs were significantly higher than in SSs, showing the highest value in the intratubular/diffuse type. Seminomas observed with neoplastic cells invasion of vessels presented higher perimeter and area values than seminomas without conformed neoplastic cells invasion.

Conclusion: In this study, we demonstrated a positive relationship between canine SE and tumor angiogenesis. Furthermore, we also showed that a tumor cells invasion of vessels were a correlated vascular parameter. Although metastasis of canine seminomas has rarely been reported, our results support that canine SE could have high metastatic potential similar to the human counterpart. Further studies are required to clarify the relationship between canine SE and clinical data with metastatic factors.

Figure 1

Canine classical intratubular/diffuse seminoma. Tumor cells in classical seminoma show PLAP-positive membranous and cytoplasmic immunostain and PAS-positive granule in cytoplasm. A. Immunoreaction of PLAP is brown with envision system-HRP. B. PAS-positive staining. Scale bar = 36 μm.

Figure 2

Immunohistochemical staining with vWF to detect microvessels and tumor cells invasion into vessels in canine seminomas. A. Microvessels in canine normal testis. B. Abundant microvessels were seen in intratubular/diffuse seminoma. C. Tumor cells invasion into lymphatic vessel is confirmed (arrow). D. Tumor emboli were seen in blood vessel (arrow). vWF is stained with envision system-HRP. Scale bar = 70 μm. BV = blood vessel; LV = lymphatic vessel.