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.

Diagnosis, Prognosis, and Treatment of Canine Hemangiosarcoma: A Review Based on a Consensus Organized by the Brazilian Association of Veterinary Oncology, ABROVET

“…The prognosis of splenic HSA in dogs is unfavorable [ 1 , 15 , 86 , 87 , 144 , 172 , 173 , 174 , 175 ] because of the high metastatic capacity of the tumor and the high rate of metastasis at the time of diagnosis. The prognostic factors with the most significant impact should be evaluated as follows: Clinical staging: patients with TI and TII staging have a longer average survival time than patients with TIII staging; the possibility of administering a chemotherapy or adjuvant protocol increases the survival time of patients who are only subjected to splenectomy.…”

“… Mitotic index (MI) of less than 11 is associated with a higher survival rate and is correlated with a slower tumor growth rate [ 176 ]. Immunohistochemical evaluation: a low expression of Ki67 (below 16%) and PSMA is associated with better survival, while CLAUDIN 5 expression is associated with an increased risk of metastasis [ 175 ]. …”

“…Immunohistochemical evaluation: a low expression of Ki67 (below 16%) and PSMA is associated with better survival, while CLAUDIN 5 expression is associated with an increased risk of metastasis [ 175 ].…”

Hemangiosarcoma in dogs as a potential non-rodent animal model for drug discovery research of angiosarcoma in humans

“…Canine HSA exhibits similar histological characteristics to human AS. The histologic features include the proliferation of immature, pleomorphic endothelial cells with expression of von Willebrand factor, CD31, claudin-5, CD117, and VEGF (57)(58)(59)(60)(61). Similarly, von Willebrand factor and CD31 are the most commonly used markers for distinguishing HSA from other malignancies.…”

Identification of genomic alterations with clinical impact in canine splenic hemangiosarcoma

“…[3][4][5][6][7][8] With respect to prognostic indicators, several have been identified for splenic HSA including tumour stage 9,10 and mitotic index. 11 More recently, other factors have been linked to outcome including expression levels of CD31, 12 expression of Claudin-5, 13 and a gene expression profile indicative of an inflammatory/immune component. 14 In the era of precision medicine, understanding the genomic landscape of HSA could facilitate identification and implementation of new, more effective therapeutic strategies with the goal of improving patient outcomes.…”