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Molecular Profile and Clinical-Pathologic Features of the Follicular Variant of Papillary Thyroid Carcinoma
An Unusually High Prevalence of ras Mutations

Zhaowen Zhu MD, PhD, Manoj Gandhi MD, Marina N. Nikiforova MD, Andrew H. Fischer MD, Yuri E. Nikiforov MD, PhD
DOI: http://dx.doi.org/10.1309/ND8D9LAJTRCTG6QD 71-77 First published online: 1 July 2003


The follicular variant (FV) of papillary thyroid carcinoma is characterized by a follicular growth pattern and cytologic features of papillary carcinoma. ret/PTC rearrangements are common in classic papillary thyroid carcinoma (PTC) and PAX8-PPARγ and ras mutations in follicular thyroid carcinoma. Their prevalence in FV has not been established. We studied these genetic alterations and clinical-pathologic features in 30 FV cases and compared those with 46 non-FV papillary carcinomas. FV cases revealed 1 ret/PTC rearrangement (3%) and 13 ras mutations (43%). Non-FV cases harbored 13 ret/PTC (28%) (P = .006) and no ras mutations (P = .0002). No PAX8-PPARγ was found in either group. FV cases demonstrated a significantly higher prevalence of tumor encapsulation, angiovascular invasion, and poorly differentiated areas and a lower rate of lymph node metastases. These data indicate that the FV of papillary carcinoma has a distinct set of molecular alterations and is characterized by a high frequency of ras point mutations.

Key Words:
  • Papillary thyroid carcinoma
  • Follicular variant
  • ras mutations
  • ret/PTC rearrangement
  • PAX8-PPARγ rearrangement