Published in Veterinary Pathology–Supplement, this study by B. Knight, G. Wood, R. Foster, and B. Coomber addresses the challenge of accurately predicting the clinical behavior of canine mast cell tumors (MCTs)—the most common skin tumor in dogs. While grading systems offer prognostic value, they cannot fully account for the wide variability in tumor behavior, highlighting the need for molecular biomarkers.
The researchers hypothesized that immunolabeling of tumor-associated biomarkers would correlate with morbidity, mortality, and treatment response. They constructed a clinically annotated tissue microarray (TMA) containing primary, recurrent, and lymph-node–metastatic dermal and subcutaneous MCTs. Dogs represented in the TMA had received either no adjunctive therapy after surgical removal or various combinations of chemotherapy, radiation therapy, or toceranib.
Immunohistochemistry for Beclin-1—a key autophagy-related protein—revealed a clear pattern: • Recurrent tumors showed higher Beclin-1 expression (mean H-score 110.8) than primary tumors (mean H-score 73.5). • Lymph node metastases had the highest expression levels (mean H-score 138.5). These differences were statistically significant (P < .001), suggesting increasing autophagy-related activity with tumor progression.
Although Beclin-1 level was not prognostic for overall disease behavior, it emerged as a strong predictive marker for survival following adjunctive therapy. Dogs with high Beclin-1–expressing tumors had markedly poorer survival than those with low expression (HR = 5.7, P = .02). The effect was even more pronounced in Kiupel high-grade MCTs (HR = 16.3, P = .01). In multivariable analysis, Beclin-1 was the only significant predictive factor (P = .04).
These findings suggest that elevated Beclin-1 expression may reflect an autophagy-dependent resistance mechanism that reduces the effectiveness of adjunctive therapies. As a result, the authors propose that autophagy inhibitors could enhance therapeutic responses for dogs with high-grade, high–Beclin-1 tumors.
Overall, this study provides compelling evidence that Beclin-1 is a valuable predictive biomarker for canine MCT treatment outcomes. Its integration into diagnostic workflows could improve clinical decision-making and guide the development of biologically targeted therapies for aggressive mast cell tumors.
Source: Knight, B., Wood, G., Foster, R., & Coomber, B. (2021). Beclin-1 is a novel predictive biomarker for canine cutaneous and subcutaneous mast cell tumors. Veterinary Pathology–Supplement. Published September 14, 2021.
