Elsevier

Journal of Comparative Pathology

Volume 165, November 2018, Pages 72-81
Journal of Comparative Pathology

Neoplastic disease
Evaluation of Histological, Immunohistochemical, Clinical and Genetic Prognostic Factors Associated with the Response of Canine Mast Cell Tumours to Glucocorticotherapy

https://doi.org/10.1016/j.jcpa.2018.10.001Get rights and content

Summary

Mast cell tumours (MCTs) are one of the most frequent neoplasms in dogs. Glucocorticoids (GCs) are widely used in the management of this disease, although no guidelines for their use have been established. The aim of this study was to evaluate the correlation of MCT prognostic factors with measurable response to GCs. This retrospective study included 60 dogs treated with prednisone or prednisolone prior to surgical biopsy of MCT. Incisional or excisional biopsy was performed 7–14 days after initiation of GC therapy. Histopathology, immunohistochemical labelling for Ki67 and KITr, and polymerase chain reaction for the c-KIT gene were performed. Partial response occurred in 63.3% of cases (38/60), while 36.7% (22/60) did not respond. A response to GCs was correlated with lower stage of the disease, low histological grade, lower pattern of KITr expression and Ki67 score. Response to GCs was positively correlated with well-established favourable prognostic factors.

Introduction

Corticosteroids are natural or synthetic cholesterol-derived hormones, physiologically produced by the adrenal gland cortex, to regulate metabolism, water and electrolyte homeostasis (Kadmiel and Cidlowski, 2013, Oppong et al., 2013). In the mid-19th century Addison described the fatal outcomes of adrenal destruction (Addison, 1855). In the 1930s, adrenocortical substances were extracted and used to treat Addison's disease (Mason et al., 1936). Studies of Steiger, Reichstein, Hench and Kendall revealed mineralocorticoid (fluid retention) and glucocorticoid (anti-inflammatory) properties and allowed the first laboratory synthesis of a corticosteroid compound, desoxycorticosterone acetate, which was successfully used to treat a patient with rheumatoid arthritis in 1948 (Steiger and Reichstein, 1937, Hench et al., 1950).

Corticosteroids are classified into mineralocorticoids, which control mineral/electrolyte and water homeostasis and glucocorticoids (GCs), named for their glucose metabolism activity, together with multiple systemic effects (Spoelhoef and Ray, 2014). Some GCs also have some mineralocorticoid activity, in addition to functions involving the immune system, cell growth and development, reproduction, haemostasis and the gastrointestinal and cardiovascular systems (Kadmiel and Cidlowski, 2013, Oppong et al., 2013, Spoelhoef and Ray, 2014).

GCs are recognized for their potent anti-inflammatory and immunosuppressive properties (Kadmiel and Cidlowski, 2013, Oppong et al., 2013) and they have also been used in the treatment of cancer for over half a century (Walsh and Avashia, 1992, Wooldridge et al., 2001, Lin and Wang, 2016). Nevertheless, most of their application in clinical oncology is the result of the clinicians' experience, rather than controlled clinical trials (Wooldridge et al., 2001, Lin and Wang, 2016).

Mast cell tumour (MCT) is one of the most frequent neoplasms in dogs. GCs are widely used in the management of this disease, but no guidelines concerning indications for their use have been established (O'Keefe, 1990; Dobson and Scase, 2007; Stanclift and Gilson, 2008). Anecdotally, it has been reported that well-differentiated MCTs show a better response to GC treatment (Rogers, 1996, Takahashi et al., 1997). The correlation between MCT response to prednisolone and other established prognostic factors has not been previously investigated.

The aim of this study was to evaluate the correlation between established prognostic factors for canine MCT with measurable clinical response to glucocorticotherapy.

Section snippets

Patient Selection and Treatment

This retrospective study included dogs treated with prednisone or prednisolone prior to surgical excision or biopsy of MCTs diagnosed through fine needle aspiration cytology. For inclusion in this study, surgery needed to be performed 7–14 days after initiation of glucocorticotherapy.

All patients underwent clinical staging by abdominal ultrasonography and cytological evaluation of regional lymph nodes when these were palpable (Blackwood et al., 2012). Cytoreductive treatment was conducted, at

Results

This study included 60 dogs aged between 4 and 16 years (mean 9.8 ± 2.9 years). Most were treated with prednisone (n = 52), but eight were treated with prednisolone. No dog had complete response, but there was partial response in 63.3% of cases (38/60) (Figs. 1a and b), while 36.7% (22/60) had no response during the short course of GCs.

Surgical excision was performed, after the short course of GCs, in 83.3% (50/60) of the dogs, 92.1% (35/38) of those with partial remission and 76.2% (15/22) of

Discussion

The lympholytic effect of GCs was first revealed in mice in 1943 (Dougherty and White, 1943), but it was soon demonstrated in people with lymphoid tumours, and in the late 1940s GCs were already available for clinical use (Stickney et al., 1950). Since then, GCs have largely been used to treat haemopoietic malignancies, such as lymphomas, lymphoblastic or lymphocytic leukaemia and multiple myeloma, in man and animals, but also solid neoplasms such as human breast and prostate cancer (Walsh and

Acknowledgments

We thank FEPMVZ (Fundacão de Estudo e Pesquisa em Medicina Veterinária e Zootecnia; Belo Horizonte, MG – Brazil), Vetpat Laboratory and Progen Biotecnologia (São Paulo, SP – Brazil), CAPES (Coordination for the Improvement of Higher Education Personnel) and CNPq (National Council for Scientific and Technological Development).

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