Dataset Information

Investigation of Prognostic Value of Claudin-5, PSMA, and Ki67 Expression in Canine Splenic Hemangiosarcoma.

ABSTRACT: Splenic hemangiosarcoma (HSA) is a malignant tumor of endothelial cells that affects middle-aged and elderly dogs and is characterized by the formation of new blood vessels, commonly associated with necrotic and hemorrhagic areas. Despite its importance in veterinary medicine, few studies have identified markers with prognostic value for canine HSA. Thus, this study aimed to associate the clinicopathological findings (prostate-specific membrane antigen [PSMA], Claudin-5, and Ki67 gene and protein expression) with overall survival in HSA-affected patients. Fifty-three formalin-fixed and paraffin-embedded canine splenic HSA samples, previously diagnosed by histopathological examination, were used in this study. Claudin-5, PSMA, and Ki67 protein expression levels were evaluated by immunohistochemistry, and gene expression was evaluated by quantitative polymerase chain reaction. Claudin-5 protein overexpression was observed in patients with metastasis (p = 0.0078) and with stage III tumors compared to those with stage I and II tumors (p = 0.0451). In patients treated with surgery alone, low PSMA gene and protein expression (p = 0.05 and p = 0.0355, respectively) were associated with longer survival time. Longer survival time was observed in patients with a low Ki67 index (p = 0.0488). Our results indicate that Claudin-5 protein expression is associated with metastatic status, and PSMA gene and protein expression, and Ki67 index are associated with survival time.

SUBMITTER: Rozolen JM

PROVIDER: S-EPMC8388721 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Investigation of Prognostic Value of Claudin-5, PSMA, and Ki67 Expression in Canine Splenic Hemangiosarcoma.

Rozolen Juliana Moreira JM Teodoro Tamires Goneli Wichert TGW Sobral Renata Afonso RA Sueiro Felipe Augusto Ruiz FAR Laufer-Amorim Renee R Elias Fabiana F Fonseca-Alves Carlos Eduardo CE

Animals : an open access journal from MDPI 20210814 8

Splenic hemangiosarcoma (HSA) is a malignant tumor of endothelial cells that affects middle-aged and elderly dogs and is characterized by the formation of new blood vessels, commonly associated with necrotic and hemorrhagic areas. Despite its importance in veterinary medicine, few studies have identified markers with prognostic value for canine HSA. Thus, this study aimed to associate the clinicopathological findings (prostate-specific membrane antigen [PSMA], Claudin-5, and Ki67 gene and protei ...[more]

PMID: 34438863

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Project description:Canine splenic hemangiosarcoma (HSA) is an aggressive tumor with a short overall survival time (OST) despite treatment with splenectomy and adjuvant doxorubicin. Modulation of the immune system has been shown to be effective for a variety of human tumors, and may be effective for canine tumors, including HSA. Immunocidin® is a non-specific immunotherapy based on a mycobacterial cell wall fraction. Preliminary work suggests Immunocidin® is safe to give intravenously (IV) in tumor-bearing dogs. This work aimed to evaluate the safety of doxorubicin and Immunocidin® combination in dogs with naturally occurring splenic HSA. A secondary aim of this study was to collect preliminary efficacy data to support a subsequent comprehensive, prospective clinical trial in canine patients with HSA, if the combination of doxorubicin and Immunocidin® was found to be safe. Eighteen dogs with stage II-III splenic HSA were recruited to receive 5 doses of sequential IV doxorubicin and Immunocidin® at two-week intervals following splenectomy. Adverse events (AEs) were graded according to the Veterinary Cooperative Oncology Group v1.1 (VCOG) scheme. Overall survival time was calculated from the date of splenectomy to date of death or loss to follow-up. AEs during administration were infrequent, the most common being hypertension. One patient developed limb and facial twitching and was removed from the study. After infusion, common AEs included lethargy, hyporexia, and diarrhea. One patient developed VCOG grade 5 diarrhea, thrombocytopenia, and anemia. Modifications in the treatment regimen were made to prevent these signs in subsequent patients. The median OST in dogs treated with the combination therapy was estimated at 147 days (range: 39-668 days). Although generally safe, the combination of doxorubicin and Immunocidin® appeared to cause more gastrointestinal effects than doxorubicin alone, and no apparent improvement in OST was noted in this population of dogs.

Project description:The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease.We first investigated mutations of VHL and Ras family genes that might drive hemangiosarcoma by sequencing tumor DNA and mRNA (cDNA). Protein expression was examined using immunostaining. Next, we evaluated genome-wide gene expression profiling using the Affymetrix Canine 2.0 platform as a global approach to test the hypothesis. Data were evaluated using routine bioinformatics and validation was done using quantitative real time RT-PCR.Each of 10 tumor and four non-tumor samples analyzed had wild type sequences for these genes. At the genome wide level, hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on a robust signature that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. This signature did not simply reflect a cancer-associated angiogenic phenotype, as it also distinguished hemangiosarcoma from non-endothelial, moderately to highly angiogenic bone marrow-derived tumors (lymphoma, leukemia, osteosarcoma).The data show that inflammation and angiogenesis are important processes in the pathogenesis of vascular tumors, but a definitive ontogeny of the cells that give rise to these tumors remains to be established. The data do not yet distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that cells which give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. We propose that the frequent occurrence of canine hemangiosarcoma in defined dog breeds, as well as its similarity to homologous tumors in humans, offers unique models to solve the dilemma of stem cell plasticity and whether angiogenic endothelial cells and hematopoietic cells originate from a single cell or from distinct progenitor cells.

Dataset Information

Investigation of Prognostic Value of Claudin-5, PSMA, and Ki67 Expression in Canine Splenic Hemangiosarcoma.

Publications

Investigation of Prognostic Value of Claudin-5, PSMA, and Ki67 Expression in Canine Splenic Hemangiosarcoma.

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