Comparative Pathology of Canine Soft Tissue Sarcomas: Possible Models of Human Non-rhabdomyosarcoma Soft Tissue Sarcomas

Milovancev, Milan; Hauck, Marlene; Keller, Charles; Stranahan, Lauren W.; Mansoor, Atiya; Malarkey, David E.

doi:10.1016/j.jcpa.2014.09.005

Cited by 26 publications

(32 citation statements)

References 13 publications

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“…Previous reports have demonstrated high histologic, immunohistochemical, and genetic similarity between human and canine STS (12, 47, 48). One drawback to the canine setting, particularly for our evaluation of the prognostic potential of CIVO, is that almost all patients are treated by surgery alone with very few receiving adjunct chemotherapy.…”

Section: Discussionmentioning

confidence: 91%

Multidrug Analyses in Patients Distinguish Efficacious Cancer Agents Based on Both Tumor Cell Killing and Immunomodulation

et al. 2017

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The vision of a precision medicine–guided approach to novel cancer drug development is challenged by high intratumor heterogeneity and interpatient diversity. This complexity is rarely modeled accurately during preclinical drug development, hampering predictions of clinical drug efficacy. To address this issue, we developed Comparative In Vivo Oncology (CIVO) arrayed microinjection technology to test tumor responsiveness to simultaneous microdoses of multiple drugs directly in a patient’s tumor. Here, in a study of 18 canine patients with soft tissue sarcoma (STS), CIVO captured complex, patient-specific tumor responses encompassing both cancer cells and multiple immune infiltrates following localized exposure to different chemotherapy agents. CIVO also classified patient-specific tumor resistance to the most effective agent, doxorubicin, and further enabled assessment of a preclinical autophagy inhibitor, PS-1001, to reverse doxorubicin resistance. In a CIVO-identified subset of doxorubicin-resistant tumors, PS-1001 resulted in enhanced antitumor activity, increased infiltration of macrophages, and skewed this infiltrate toward M1 polarization. The ability to evaluate and cross-compare multiple drugs and drug combinations simultaneously in living tumors and across a diverse immunocompetent patient population may provide a foundation from which to make informed drug development decisions. This method also represents a viable functional approach to complement current precision oncology strategies.

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Section: Discussionmentioning

confidence: 91%

Multidrug Analyses in Patients Distinguish Efficacious Cancer Agents Based on Both Tumor Cell Killing and Immunomodulation

et al. 2017

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“…8 In contrast, another recent article reported that 2 poorly differentiated canine liposarcomas were immunoreactive to a muscle marker (ie, desmin), but these poorly differentiated tumors were not confirmed to be liposarcoma with lipid stains. 19 Potential misdiagnosis of liposarcoma as rhabdomyosarcoma has prognostic significance as rhabdomyosarcomas have a particularly poor prognosis. Further, liposarcoma is graded using the scheme for canine STS, whereas rhabdomyosarcoma is excluded from this grading scheme.…”

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confidence: 99%

Immunoreactivity of Canine Liposarcoma to Muscle and Brown Adipose Antigens

LaDouceur

Stevens

Wood³

et al. 2017

Vet Pathol

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Liposarcoma, rhabdomyosarcoma, and hibernoma share some overlapping histologic and immunohistochemical features. Although immunohistochemistry (IHC) is commonly used in the diagnosis of these neoplasms, expression of muscle markers has been reported in human liposarcoma and canine hibernoma in addition to rhabdomyosarcoma. Thus, these neoplasms are a diagnostic challenge but important to distinguish because of differences in prognosis and treatment. Rhabdomyosarcoma and liposarcoma are both malignant, but rhabdomyosarcoma has a higher potential for metastasis. In contrast, hibernomas are benign with low risk of recurrence. This study investigated expression of the muscle markers desmin, myogenin, and α-smooth muscle actin (α-SMA) and the brown fat marker uncoupling protein 1 (UCP1) in 25 cases of canine liposarcoma using IHC. Oil red O histochemistry was performed to confirm the presence of lipid and the diagnosis of liposarcoma in cases that were not well-differentiated. The 25 cases included 15 well-differentiated, 5 pleomorphic, 3 myxoid, and 2 dedifferentiated subtypes of liposarcoma. By IHC, 23 of 25 expressed UCP1, 7 of 25 expressed α-SMA, 7 of 25 expressed desmin, and 3 of 25 expressed myogenin with no clear relationship of antigen expression and tumor subtype. These findings clarify the immunohistochemical profile of canine liposarcoma and suggest overlap in the expression of several muscle antigens and UCP1 between liposarcoma, hibernoma, and rhabdomyosarcoma.

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“…Current identification of specific molecular markers (or panels of markers) with clinical prognostic significance might be limited by individual tumour‐ and patient‐specificity . Although there is a paucity of literature that is directly applicable to veterinary molecular margins, close parallels between human and canine cancers suggest that these concepts might also be applicable to veterinary patients …”

Section: Future Directionsmentioning

confidence: 99%

Surgical margins in the veterinary cancer patient

Milovancev

Russell

2017

Vet Comparative Oncology

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In veterinary oncologic specimens, histopathology is the gold standard for determining adequacy of excision. Despite limitations of this technique, the pathologist's interpretation of margin status significantly impacts patient management, including indications for adjuvant therapy. This article aims to summarize peer-reviewed literature as it relates to histologic margin evaluation in veterinary cancer patients. The value of histologic tumour-free margins and technical factors influencing histopathologic margin outcomes are also discussed. We review alternative strategies for determining excisional status, and discuss how an evolving understanding of tumour biology might inform clinical and research perspectives on surgical margins. In doing so, we aim to provide context and a stimulus for future investigations into this important yet incompletely understood topic.

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Comparative Pathology of Canine Soft Tissue Sarcomas: Possible Models of Human Non-rhabdomyosarcoma Soft Tissue Sarcomas

Cited by 26 publications

References 13 publications

Multidrug Analyses in Patients Distinguish Efficacious Cancer Agents Based on Both Tumor Cell Killing and Immunomodulation

Multidrug Analyses in Patients Distinguish Efficacious Cancer Agents Based on Both Tumor Cell Killing and Immunomodulation

Immunoreactivity of Canine Liposarcoma to Muscle and Brown Adipose Antigens

Surgical margins in the veterinary cancer patient

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