The classic nuclear features of papillary thyroid carcinoma (PTC) include Orphan Annie eye nuclei and nuclear grooves. The molecular mechanism underlying most sporadic PTCs involves constitutive activation of which signalling pathway?
- A PI3K-AKT-mTOR pathway via PIK3CA mutation
- B MAPK (RAF-MEK-ERK) pathway via BRAF V600E mutation or RET/PTC rearrangement ✓
- C Wnt-beta-catenin pathway via CTNNB1 mutation
- D JAK2 V617F mutation activating the JAK-STAT pathway
Explanation
Approximately 70% of sporadic PTCs harbour BRAF V600E point mutation, which constitutively activates the MAPK (RAF-MEK-ERK) signalling cascade, driving thyroid epithelial proliferation and dedifferentiation. RET/PTC chromosomal rearrangements (especially common in radiation-induced PTCs) also activate the same MAPK pathway. These two oncogenic alterations (BRAF V600E and RET/PTC) are mutually exclusive, suggesting they converge on the same pathway. PI3K-AKT pathway alterations (PTEN loss, PIK3CA mutation) are more characteristic of follicular carcinoma. CTNNB1 mutations occur in anaplastic thyroid carcinoma.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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