Prognostic value of immunohistochemical markers in canine cutaneous mast cell tumours: A systematic review and meta‐analysis

Abstract

Histological grading systems remain cornerstones in the prognosis of canine cutaneous mast cell tumours (MCTs), but the distinct biological behaviour of each tumour often necessitates the use of complementary markers. Although a plethora of immunohistochemical markers have been proposed as prognostic factors, few are presently applied in routine diagnosis. This systematic review and meta‐analysis was designed to establish which immunohistochemical markers have verifiable prognostic value for cutaneous MCTs in dogs. A Boolean search of five databases identified 200 articles for screening, of which 73 were selected for full‐text assessment and 24 ultimately included in the systematic review. Odds Ratio (OR) was adopted as the summary measure for subsequent meta‐analysis but only 15 articles, relating to the immunomarkers Ki‐67 (9), KIT (5), and BAX (2), provided either a value for OR or sufficient data to calculate this statistic. Meta‐analysis verified that canine cutaneous MCTs with elevated expression of Ki‐67 or BAX, as well aberrant immuno‐expression of KIT, showed an increased odds of death, with respective OR values of 11.2 (95% CI 6.3‐20.0; p < .01), 9.9 (95% CI 1.3‐73.6; p = .03), and 4.1 (95% CI 1.1‐15.3; p = .03). Despite KIT, Ki67, and BAX arise as suitable prognostic factor for canine MCTs, this study highlighted the lack of important clinical and statistical data in many published articles, rendering it impossible to complete the meta‐analysis of several potentially valuable immunohistochemical markers.

Diagnosis, Prognosis and Treatment of Canine Cutaneous and Subcutaneous Mast Cell Tumors

“…However, in the study by Scase and colleagues [ 107 ], although AgNOR and Ki-67 levels had prognostic value, PCNA expression showed no correlation with prognosis. Freytag et al [ 146 ] carried out an extensive review and meta-analysis aiming to identify the immunohistochemical markers that have the greatest prognostic value in this context to date. They observed that Ki-67 and KIT expression have prognostic value, and the pro-apoptotic immunomarker BAX also showed promising application as a prognostic factor in MCTs.…”

Evaluation of Tumor Grade and Proliferation Indices before and after Short-Course Anti-Inflammatory Prednisone Therapy in Canine Cutaneous Mast Cell Tumors: A Pilot Study

“…Mast cell tumors (MCTs) are the most common skin tumor affecting dogs, and the tumor grade is the most consistent and clinically relevant prognostic factor [1][2][3][4]. There are two MCT grading systems: the Patnaik system and the Kiupel system [3].…”

“…Ki67 is a nuclear protein that is expressed in all phases of the cell cycle except G0 and represents the tumor growth fraction. The relative number of cells expressing Ki67 is an established prognostic factor in canine MCTs and other malignancies in several species [2,11]. There are multiple variants of Ki67, with species, cell-type, and cell-cycle specificity, and it forms the perichromosomal layer during mitosis, preventing chromosomes from sticking together and maintaining chromosomal structural integrity.…”

“…A silver-based staining method is used to identify and quantify NORs, termed argyrophilic nucleolar organizing regions (AgNOR), and represents how quickly the cells progress through the cell cycle. Together, AgNOR and Ki67 further refine the anticipated biological behavior and can provide the clinician with information to guide treatment decisions for patients with tumors with the intermediate tumor grades of G2/LG and G2/HG [2].…”

“…The prognosis and subsequent management of the patient after definitive local therapy is dichotomized by the MCT grade. Typically, low-grade tumors require no further treatment, even if incompletely excised, and patients are expected to have good to excellent outcomes, while patients with high-grade tumors are expected to succumb to their disease and require intensive multi-modal therapeutic strategies [1,2,6,[35][36][37][38][39]48,[52][53][54][59][60][61][62][63][64][65][66][67]. This then raises the question of how preoperative glucocorticoid treatment may impact the histological parameters and criteria for grade determination and the immunohistochemical detection of proliferation indices in canine MCTs.…”