Evaluation and analysis of canine digital cell carcinoma - Histological grading correlation to microscopic features of malignancy in the invasive front and copy number variation of the KIT ligand | Digitales Plattenepithelkarzinom des Hundes und seine genetische Faktoren – Eine histologische Bewertung von digitalen Plattenepithelkarzinomen bei Hunden unter Berücksichtigung der Fellfarbe und der Korrelation mit der Kopienzahlvariation des KIT-Liganden-Gens

Canine digital squamous cell carcinomas (CDSCC) tend to behave more aggressively than other areas of the skin. Furthermore, CDSCC in dark-haired animals are more biologically aggressive than in light-haired animals. However, up to date there is no standardized histological evaluation and comparison of DSCC morphology between dark and light breeds. In addition, dark-haired dogs have a known predisposition to develop DSCC. Additionally, some studies have suggested that dogs with a copy number > 4 in the KITLG locus, which is associated with melanogenesis, have an increased susceptibility to the development of DSCC. However, if the KITLG copy number had an effect on the morphology and histopathological features of DSCC still remains largely unknown. Study 1 included the histological evaluation of DSCC from 94 dogs, divided into two groups, (1) dark-haired (n = 76) and (2) light-haired breeds (n = 18). Group 1 was further subdivided into three subgroups, (1a) various black-haired breeds (n = 11), (1b) black Schnauzers (n = 34) and (1c) black & tan breeds (n = 31). For an objective evaluation, two known grading schemes for squamous cell carcinomas were used comparatively. As a result, both histological grading systems exhibited significant differences between groups 1 and 2. Digital SCC of the light-haired dogs were consistently better differentiated than those of group 1. There were no significant differences between the different dark-haired breeds in any of the individual characteristics assessed (invasive front, degree of invasion, nuclear pleomorphism, tumor cell buds, smallest tumor nest size and amount of tumor stroma). For study 2, 70 blood samples were collected from dogs with DSCC (partially overlapping with study 1). This study was designed to test whether and to what extent the previously evaluated histologic grades correlated with the number of copies KITLG locus determined by ddPCR. For the second study, the grouping was established as follows; 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 & tan dogs (n = 7); group 2/light-haired animals (n = 4). The results showed a significant correlation between increased KITLG copy number and more malignant histologic grading. This suggests that KITLG may have a role in the development of DSCC by causing different, more aggressive morphologic features. The compilation of these two studies may help to better characterize and understand canine squamous cell carcinoma of the toe. By taking genetic predispositions into account, a better and individualized assessment of the risk of disease in black dogs and thus earlier treatment is possible.