<p>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 <i>TP53</i> mutations, respectively. T lymphocytes (CD3<sup>+</sup>), regulatory T cells (FoxP3<sup>+</sup>), B lymphocytes (CD20<sup>+</sup>), and macrophages (IBA-1<sup>+</sup>) 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 <i>TP53</i> mutations were found in 13/29 cases (44.83%), of which 18/21 were C &gt; T base substitutions, typical of ultraviolet (UV)-induced DNA damage. In tumors with <i>TP53</i> mutations, IBA-1⁺ macrophages were significantly increased (<i>p</i> = 0.001) and CD3⁺ T lymphocytes were also more abundant (<i>p</i> = 0.028) than in wild type <i>TP53</i> cases, whereas CD20⁺ B lymphocytes and FoxP3⁺ regulatory T lymphocytes showed no significant differences. <i>Equus caballus</i> 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 with<i>TP53</i> mutations, but the difference was not statistically significant. Overall, <i>TP53</i> mutations appear to contribute to eoSCC development, potentially as a consequence of UV-light exposure, and to influence immune cell infiltration.</p>

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

  • Ginevra Martinoli,
  • Dario De Biase,
  • Lorenzo Ressel,
  • Barbara Brunetti,
  • Giancarlo Avallone,
  • Alessia Grillini,
  • Tania Franceschini,
  • Michelangelo Fiorentino,
  • Giuseppe Sarli,
  • Barbara Bacci

摘要

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.