For which Kiupel histological group is beclin-1 most useful as a predictive biomarker, and why?

• A. Kiupel high-grade MCTs. Because beclin-1 identifies which high-grade tumors are resistant to treatment, guiding intensive adjunctive therapy
• B. Kiupel low-grade MCTs, which are rarely resistant
• C. All Kiupel groups equally, since beclin-1 is universally predictive
• D. Kiupel intermediate-grade MCTs, which are the most variable

Answer: (A)

Beclin-1 is a key regulator of autophagy, a cellular recycling process that cancer cells can harness to survive stress from therapy. In canine mast cell tumors, the Kiupel high-grade group represents tumors that are most aggressive and most prone to treatment resistance. When beclin-1 activity signals autophagy-driven survival, it helps identify which high-grade tumors are likely to resist standard treatment, guiding the use of more intensive adjunctive therapies. In contrast, low-grade tumors are typically already responsive, and intermediate-grade tumors are more variable, so the predictive value of beclin-1 is less robust in those groups. Therefore, beclin-1 is most useful as a predictive biomarker in high-grade MCTs, where knowing resistance risk has the greatest impact on management.