Evaluating the Histologic Grade of Digital Squamous Cell Carcinomas in Dogs and Copy Number Variation of KIT Ligand—A Correlation Study

Abstract

Dark-haired dogs are predisposed to the development of digital squamous cell carcinoma (DSCC). This may potentially suggest an underlying genetic predisposition not yet completely elucidated. Some authors have suggested a potential correlation between the number of copies KIT Ligand (KITLG) and the predisposition of dogs to DSCC, containing a higher number of copies in those affected by the neoplasm. In this study, the aim was to evaluate a potential correlation between the number of copies of the KITLG and the histological grade of malignancy in dogs with DSCC. For this, 72 paraffin-embedded DSCCs with paired whole blood samples of 70 different dogs were included and grouped according to their haircoat color as follow: Group 0/unknown haircoat color (n = 11); Group 1.a/black non-Schnauzers (n = 15); group 1.b/black Schnauzers (n = 33); group 1.c/black and tan dogs (n = 7); group 2/tan animals (n = 4). The DSCCs were histologically graded. Additionally, KITLG Copy Number Variation (CNV) was determined by ddPCR. A significant correlation was observed between KITLG copy number and the histological grade and score value. This finding may suggest a possible factor for the development of canine DSCC, thus potentially having an impact on personalized veterinary oncological strategies and breeding programs.

KITLG Copy Number Germline Variations in Schnauzer Breeds and Their Relevance in Digital Squamous Cell Carcinoma in Black Giant Schnauzers

“…A KITLG copy number value >4 was found to be correlated with a predisposition to dSCC in black standard poodles compared with light-coloured standard poodles [ 35 ]. In a recent study, we found that 55 black-coated and black and tan dogs with dSCC had mean copy number values ranging from 5.5 to 5.8 in contrast to four light-coated animals with dSCC that had a mean copy number value of 4.5 [ 16 ]. Interestingly, this study has shown that there is a predictive correlation between higher germline KITLG copy number values and increased histological aggressiveness of digital SCC in dogs (mainly black-coated breeds and black and tan breeds) [ 16 ].…”

“…Dark coat colour is correlated to the development and aggressiveness of squamous cell carcinoma [ 1 , 2 , 3 , 4 , 5 , 6 , 13 , 16 ]. A predisposition for squamous cell carcinoma in standard schnauzers (SS) and giant schnauzers (GS) has been identified by various authors [ 1 , 4 , 5 , 6 , 17 ].…”

Comparative Study of Digital Squamous Cell Carcinoma in Giant, Standard, and Miniature Schnauzers

“…A copy number variation (CNV) at the KITLG gene is responsible for coat colour intensity [ 27 ]. Furthermore, the CNV at the KITLG gene is associated with the predisposition to digital SCC in black poodles [ 28 ] and black giant schnauzers [ 29 ], as well as with the degree of the digital SCC’s histological aggressiveness [ 30 ]. However, other genetic factors may play a role, suggesting that there are multiple pathways leading to the final oncogenesis of digital SCC [ 28 ].…”

“…However, in the literature on digital SCC, there is only one study on 38 cases of digital SCC in schnauzers, which included 12 GSs (32%), 24 SSs (63%), and 2 MSs (5%) [ 31 ]. Most other publications made no distinction of the schnauzer size variants for specific clinical or pathological parameters [ 3 , 9 , 12 , 30 ]. Thus, the aim of the present study is to compare the clinical and macroscopic findings of digital SCC in giant, standard, and miniature schnauzers based on a high number of cases.…”