Comparative Analysis of mRNA Expression of Surface Antigens between Histiocytic and Nonhistiocytic Sarcoma in Dogs

Abstract

Background: Definitive diagnosis of histiocytic sarcoma (HS) in dogs is relatively difficult by conventional histopathological examination because objective features of HS are not well defined.Hypothesis: Quantitative analysis of mRNA expression of selected cellular surface antigens (SAs) specific to HS in dogs can facilitate objective and rapid diagnosis.Animals: Dogs with HS (n = 30) and dogs without HS (n = 36), including those with other forms of lymphoma (n = 4), inflammatory diseases (n = 6), and other malignant neoplasias (n = 26).Methods: Retrospective clinical observational study. Specimens were collected by excisional biopsy, needle core biopsy, or fine needle aspiration. To determine HS detection efficacy, mRNA expression levels of selected SAs specific to HS in dogs, including MHC class IIa, CD11b, CD11c, and CD86, were quantitatively analyzed using real-time quantitative polymerase chain reaction.Results: Each SA mRNA expression level was significantly higher in HS dogs than in non-HS dogs (P = .0082). Cutoff values for discriminating between HS and non-HS dogs based on these expression levels were calculated on the basis of receiver-operating characteristic analysis. Accuracy of the cutoff values, including MHC class IIa, CD11b, CD11c, and CD86, was 87.9, 86.4, 86.4, and 84.8%, respectively. Conclusions and Clinical Importance: Our results suggest that quantitative analysis of mRNA expression of the selected SAs could be an adjunctive diagnostic technique with high diagnostic accuracy for HS in dogs. Substantial investigation is required for exclusion of diseases with similar cell types of origin to lymphoma.

Survivin suppressor (YM155) enhances chemotherapeutic efficacy against canine histiocytic sarcoma in murine transplantation models

“…Hemophagocytic HS originating from macrophages arises from splenic tissue. Dogs with HS (hereafter referred to as HS dogs) exhibit generally poor treatment outcomes because of the tumor's aggressive biological behavior, including its high cell proliferation, multidrug resistance, and metastatic potential (Yamazaki et al, 2013(Yamazaki et al, , 2014. Lomustine (CCNU) or doxorubicin have been commonly used as antitumor agents for HS dogs (Rassnick et al, 2010); however, the therapeutic benefit on the disseminated and hemophagocytic HS is insufficient because of resistance to these drugs (Klahn et al, 2011;Rassnick et al, 2010).…”

Influence of a survivin suppressor YM155 on the chemoresistance of canine histiocytic sarcoma cells

“…Enhanced survivin expression may play a role in the mechanism underlying chemoresistance acquisition (Rödel et al, 2012). We previously reported that suppressing survivin expression enhanced growth inhibition and CCNU sensitivity of canine HS cells (Yamazaki et al, 2013). These findings supported the hypothesis that survivin inhibition enhanced antitumor effects and chemotherapy efficacy.…”

“…For qRT-PCR assay, primers for survivin (5′-TCGAAGAGACCGCAAAGAAAGTGC-3′ and 5′-GAATTGTGGCCGTTCTCCTTTCCT-3′, 181 bp, GenBank accession number AY741504) (Yamazaki et al, 2013) and its internal reference hypoxanthine phosphoribosyltransferase 1 (HPRT; 5′-TGCTCGAGATGTGATGAAGG-3′ and 5′-TCCCCTGTTGACTGGTCATT-3′, amplicon size 192 bp, GenBank accession number NM001003357) were used. We performed qRT-PCR assays using a Rotor-Gene Q (Qiagen) and KAPA SYBR FAST qPCR Master Mix (KAPA Biosystems) according to the manufacturer's instructions.…”

“…Lomustine (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea; CCNU) is a commonly used antitumor agent for treating HS in dogs (Rassnick et al, 2010). Clinically, most HS dogs acquire chemoresistance during early stages of chemotherapy, resulting in poor survival outcomes (Yamazaki et al, 2013). It has been suggested that chemoresistance is enhanced by the expression and function of chemoresistance-related genes, including inhibitor of apoptosis protein (IAP) and ATP-binding cassette (ABC) transporters (Nakagawa et al, 2006).…”

“…Histiocytic sarcoma (HS) in dogs is a malignant tumor that is characterized by aggressive local infiltration and an extremely high metastatic rate (Yamazaki et al, 2014). Lomustine (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea; CCNU) is a commonly used antitumor agent for treating HS in dogs (Rassnick et al, 2010).…”