PDGFRβ Expression Across Canine AGASAC Subtypes and Metastases: Morphologic Insights and Possible Therapeutic Implications

Canine apocrine gland anal sac adenocarcinoma (AGASAC) is an aggressive malignancy with a high incidence of regional lymph node metastasis at diagnosis. Platelet-derived growth factor receptor beta (PDGFRβ) is a receptor tyrosine kinase involved in oncogenic signaling and angiogenesis, representing a potential therapeutic target. Its expression in different AGASAC histotypes has not been fully defined. This study evaluated microscopic patterns and PDGFRβ immunohistochemical expression in three normal anal gland sacs, 51 primary AGASACs (12 non-metastatic, 39 metastatic), and 33 corresponding nodal metastases. PDGFRβ expression was semi-quantitatively scored and statistically analyzed. Histotypes included 26 mixed with solid prevalence, 11 pure solid (including 1 comedo-carcinoma), 9 mixed with tubular prevalence, 4 tubular, and 1 neuroendocrine-like. PDGFRβ was expressed in normal anal sac glands and in 43/51 tumors (5-100% positive cells): 19/26 mixed with solid prevalence, 10/11 solid, 9/9 mixed with tubular prevalence, 4/4 tubular, and 1 neuroendocrine-like. PDGFRβ labeled 27/33 nodal metastases. PDGFRβ expression was highest and more intense in tumors with a tubular pattern. The statistical trend indicated a correlation of AGASAC dedifferentiation to reduced PDGFRβ expression, but no statistical significance was found. Rare AGASAC variants (solid comedo-carcinoma and neuroendocrine-like) were described for the first time. PDGFRβ expression was higher in tubular tumors and commonly detected in primary and metastatic lesions. These findings support exploring TKI therapy for specific AGASAC histotypes. Further studies integrating receptor activation and treatment outcomes are warranted to clarify predictive and prognostic relevance.