A tumor expressing strong nuclear positivity for beta-catenin on immunohistochemistry most likely harbors a mutation in which signaling pathway component?

• A KRAS
• B APC or CTNNB1 (beta-catenin itself) ✓
• C TP53
• D SMAD4

Explanation

Nuclear accumulation of beta-catenin indicates activation of the Wnt/beta-catenin signaling pathway. In the absence of Wnt signaling, the destruction complex (APC, Axin, GSK3beta) phosphorylates beta-catenin, targeting it for proteasomal degradation. Loss-of-function mutations in APC or gain-of-function mutations in CTNNB1 (encoding beta-catenin) prevent degradation, causing nuclear translocation and transcriptional activation of proliferation genes. This is the hallmark of colorectal adenomas/carcinomas and hepatoblastomas.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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