Association between ultraviolet-related TP53 mutations and immune microenvironment in equine ocular squamous cell carcinoma

This study investigates the molecular and immune characteristics of equine ocular squamous cell carcinoma (eoSCC). Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to detect protein expression and TP53 mutations, respectively. T lymphocytes (CD3(+)), regulatory T cells (FoxP3(+)), B lymphocytes (CD20(+)), and macrophages (IBA-1(+)) were quantified. A total of 29 cases of eoSCC were evaluated, consisting of 3/29 carcinomas in situ (CISs) and 26/29 squamous cell carcinomas (SCCs). p53 positivity by IHC was detected in 19/29 cases while by NGS, 21 TP53 mutations were found in 13/29 cases (44.83%), of which 18/21 were C > T base substitutions, typical of ultraviolet (UV)-induced DNA damage. In tumors with TP53 mutations, IBA-1(+) macrophages were significantly increased (p = 0.001) and CD3(+) T lymphocytes were also more abundant (p = 0.028) than in wild type TP53 cases, whereas CD20(+) B lymphocytes and FoxP3(+) regulatory T lymphocytes showed no significant differences. Equus caballus papillomavirus type 2 positivity was detected in 6/29 cases (20.69%) via in situ hybridization (ISH), but viral presence did not impact immune cell infiltration. Ki67 scores were higher in SCCs/CISs withTP53 mutations, but the difference was not statistically significant. Overall, TP53 mutations appear to contribute to eoSCC development, potentially as a consequence of UV-light exposure, and to influence immune cell infiltration.