Assessment of P-Glycoprotein Expression in Canine Soft Tissue Sarcomas

Caroline Hohlman

doi:10.7273/000006398

Objective: Determine the level of P-glycoprotein (P-gp) expression via Western blots of protein extracts of soft tissue sarcomas (STS) in chemotherapy-naïve dogs sampled at the Washington State University Veterinary Teaching Hospital from July 2021 until October 2022. Procedures: STS samples were obtained via excisional biopsy performed by the Washington State University Veterinary Teaching Hospital Surgery service on 22 cases. Samples were selected based on the following criteria: 1) pre-operative diagnosis or suspicion of STS 2) adequate tumor volume and 3) clients willing to pursue attempted surgical excision or surgical biopsy for definitive diagnosis of an STS and thus P-gp testing. Information regarding histopathologic grade was obtained in all 22 of the excisional biopsy samples. All samples were obtained fresh at the time of surgery and flash frozen in liquid nitrogen for 20 minutes prior to being stored in an –80°C freezer until Western blot processing. Western blots on protein extracts from STS samples were run in conjunction with beta actin Western blots to confirm consistent loading of the wells. This project utilized tissue samples obtained in the clinical staging or treatment of the affected patient, so interventions solely to acquire samples for this study were not needed. Results: Twenty-two canine patients met the inclusion criteria with one patient having had two tumors removed from different locations in a single surgery. Histopathologic evaluation was available for 22/23 tissue samples with the 23rd having been lost post-operatively. However, this sample was consistent with a spindle cell neoplasia on cytology prior to removal and thus was still included in this study. Histologic grade within the STS umbrella included 9 grade 1 tumors, 7 grade 2 tumors, and 4 grade 3 tumors. Two tumors were classified as oral fibrosarcomas and one sample classified as a spindle cell neoplasm via two cytology reports. The remaining samples were STS under the umbrella use of the term STS (n = 16) without a diagnosis of specific type of STS, and 4 samples were given a diagnosis of a specific tumor type under the STS umbrella: hemangiopericytoma (n=2), liposarcoma (n=1) and myxosarcoma (n=1). Western blots identified P-gp expression in samples from 7 STS with the remaining 16 having no visible P-gp expression. Conclusions and clinical relevance: These results indicate that a subset of chemotherapy-naïve canine STS constitutively express P-gp prior to chemotherapy administration. The clinical significance of this finding should be explored further to determine if P-gp expression by STS correlates with inherent chemotherapy resistance of STS, particularly regarding P-gp substrates (e.g. doxorubicin) or if P-gp expression correlates with prognosis.

Assessment of P-Glycoprotein Expression in Canine Soft Tissue Sarcomas

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