Extensive necrosis of spontaneous canine mammary adenocarcinoma after extracorporeal perfusion over Staphylococcus aureus Cowans I. I. Description of acute tumoricidal response: morphologic, histologic, immunohistochemical, immunologic, and serologic findings.

Abstract

Abstract Morphologic, histologic, immunohistochemical, and serologic changes were recorded in dogs with spontaneous breast adenocarcinoma after extracorporeal perfusion of plasma over heat-killed and formalin-stabilized Staphylococcus aureus Cowans I (SAC), which was embedded in a membrane filtration system. Whole blood was passaged into a continuous flow cell-separator in which plasma and formed elements were partitioned, and plasma was selectively circulated over SAC, 1 g/kg body weight, at a flow rate of 15 to 30 ml/min. In 12 dogs, gross and microscopic tumor necrosis was observed beginning 4 hr after perfusion. By 24 hr after perfusion, multiple visible lesions in six of six dogs exhibited extensive necrosis, but there was no reaction in uninvolved normal mammary tissue. In eight dogs, healing of large ulcerated areas of cutaneous tumor was observed within 8 to 18 days after perfusion. Microscopically, tumor cell necrosis with minimal leukocytic elements was observed 4 hr after extracorporeal perfusion associated with immunohistochemical deposits of IgG and C3 and ultrastructural evidence of lytic lesions on tumor cell membranes. Extensive infiltration of necrotic areas of tumor by leukocytes was noted 48 hr after perfusion. Toxicity of the procedure included mild fever in 6 of 12 dogs and leukocytosis, which were transient and abated spontaneously. No tumoricidal effects were observed after perfusion over Staphylococcus aureus Woods (SAW) (nonprotein A bearing) in three dogs that previously or subsequently responded to SAC perfusion. SAC but not SAW perfusion was followed by increases in circulating tumor-specific antibodies (TSA) for up to 48 hr after perfusion. Serum IgG and C3 levels declined after SAC perfusion. IgG subsequently rebounded above preperfusion levels, whereas C3 values were sustained below pretreatment levels for up to 48 hr. Immune complexes rose after perfusion and remained elevated for 72 hr. There was no significant release of 125I SAC from the extracorporeal circulation system. Findings taken together suggest that the acute tumoricidal response may be initiated by TSA that are rendered operational or freshly generated after extracorporeal perfusion over SAC. Finally, the rapidity, specificity, and magnitude of the observed tumoricidal effects with minimal host toxicity suggests that this extracorporeal modality may represent a potentially effective therapeutic instrument in canine breast adenocarcinoma.