Evaluation of prognostic markers for canine mast cell tumors treated with vinblastine and prednisone

Abstract

Background: Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease associated with a variable biologic behavior. Surgery remains the primary treatment for canine MCT; however, radiation therapy (RT) and chemotherapy are commonly used to treat aggressive MCT. The goals of this study were to evaluate the prognostic utility of histologic grade, c-KIT mutations, KIT staining patterns, and the proliferation markers Ki67 and AgNORs in dogs postoperatively treated with vinblastine and prednisone +/-RT, and to compare the outcome of dogs treated with post-operative chemotherapy +/-RT to that of a prognostically matched group treated with surgery alone. Associations between prognostic markers and survival were evaluated. Disease-free intervals (DFI) and overall survival times (OS) of dogs with similar pretreatment prognostic indices postoperatively treated with chemotherapy were compared to dogs treated with surgery alone.

c-KIT messenger RNA and protein expression and mutations in canine cutaneous mast cell tumors

“…20,22,27 The presence of aberrant cytoplasmic KIT localization has been correlated with a reduced post-surgical survival. 10,25 A large number of c-KIT mutations have been identified in canine MCTs, mostly localized in exon 11, 8,15,19,29,38,40,42 occasionally in exons 8 and 9, 15 and sometimes in exon 17.…”

“…41 To improve concordance among pathologists and to provide better prognostic significance, a 2-tier histologic grading system has been proposed. 9 Other prognostic markers including microvessel density, 27 mitotic index, 27,30 and markers of cellular proliferation and growth rate, such as argyrophilic nucleolar organizer regions, proliferating cell nuclear antigen, and MKi-67 immunoreactivity 31,32,40 have been investigated in canine MCT. The study of the c-KIT receptor (KIT or cluster of differentiation [CD]117) has been recently done to explain the pathogenesis of canine cutaneous MCTs.…”

Proposal of a 2-Tier Histologic Grading System for Canine Cutaneous Mast Cell Tumors to More Accurately Predict Biological Behavior

“…17 However, a recent study documented that high-grade MCTs lacking mutations or aberrant KIT expression responded to a chemotherapy protocol composed of vinblastine and prednisone. 19 The proposed 2-tier grading system should be applied as an initial screening tool at the time of routine histologic examination and diagnosis of a cutaneous MCT. With this grading system, those tumors that pose a high risk of aggressive behavior can be immediately identified, which would allow the owner and veterinary clinician to request supplemental testing (eg, expression of KIT or screening for c-KIT mutations) to select the most appropriate therapy.…”

Outcome of adjuvant chemotherapy with lomustine, vinblastine and chlorambucil on management of canine mast cell tumour of high to intermediate risk

“…Despite the many proposed drugs for chemotherapy in dogs with MCT, their use remains empirical (Dobson and Scase, 2007;London and Thamm, 2013) and the combination of vinblastine and prednisone appears to have become the protocol of choice (Dobson and Scase, 2007;Webster et al, 2008). In the study conducted by Thamm et al (2006), 61 high-risk patients (intermediate to high grade MCT, located in mucocutaneous junctions or with regional lymph node involvement), received adjuvant treatment with intravenous vinblastine at a dosage of 2 mg/m 2 every seven or 14 days, combined with prednisone, resulting in a median survival of 1374 days for grade 3 MCT, whereas all patients with grade 2 MCT reached the survival of three years.…”

“…Other prognostic factors, may also be important for disease progression, such as tumour location (scrotum, prepuce, perineum or vulva), breed (London and Thamm, 2013) and KITr pattern expression (Kiupel et al, 2004). Specific gainof-function genetic mutations are also largely associated with worse prognosis (Zemke et al, 2002;Webster et al, 2006;Webster et al, 2008;Avery, 2012).…”