Centrosome Overduplication in Canine Hemangioma and Hemangiosarcoma

Abstract

Centrosome overduplication (more than 2; >2C) is commonly associated with aneuploidy in many human cancers and is theorized to contribute to malignant transformation via increased chromosomal instability. >2C is not been described in endothelial cell (EC) tumors such as hemangioma (HA) and hemangiosarcoma (HSA). HAs are common, benign canine tumors that may undergo malignant transformation to HSA through unknown cellular mechanisms. To characterize the possible contribution of >2C to the development of HSA, archived formalin‐fixed paraffin‐embedded canine tissue (5‐8 uM thick) with a previous diagnosis of HA (n=4) or HSA (n=6) from the subcutis, spleen or liver were labeled with EC (isolectin) and centrosome (gamma‐tubulin) markers by immunofluorescence. Samples were imaged via confocal microscopy and quantified as % of neoplastic EC with >2C. HSAs had significantly greater >2C compared with HAs (20.1+/‐ 1.4% vs 4.4 +/‐ 2.3%; p<0.001). HA and control tissues did not demonstrate differences in >2C (controls 2.8 +/‐ 1.0%; p=0.24). Percentage of >2C cells in subcutaneous or visceral HSA was not different (18.2 +/‐ 1.1 vs 23.6 +/‐ 2.8; p=0.11). A subset of subcutaneous tissues (n=2) demonstrated regions of both HA and HSA morphology (HSA: increased mitotic rate, pleomorphism, solid growth); within the same tissue, areas of HSA morphology had significantly greater >2C compared with areas of HA morphology (27.6 +/‐ 3.0% vs 5.9 +/‐ 4.9%; p=0.003). These results support an association of >2C with phenotypic malignancy in canine endothelial cell neoplasms; thus, centrosome overduplication may contribute to transformation of neoplastic endothelial cells in canine HSA.