Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas

Adebowale J. Adeniran, Zhaowen Zhu, Manoj Gandhi, David L. Steward, James P. Fidler, Thomas J. Giordano, Paul Williams Biddinger, Yuri E. Nikiforov

Research output: Contribution to journalArticle

357 Citations (Scopus)

Abstract

Papillary carcinoma is the most common type of thyroid malignancy. It has been recently shown that these tumors commonly have one of three genetic alterations: BRAF point mutations, RET/PTC rearrangements, or RAS point mutations. In this study, we analyze the relationship between these alterations and the microscopic features of papillary carcinomas, their clinical features, and prognostic characteristics. Ninety-seven papillary carcinomas were studied; in all cases, frozen tissue was available for nucleic acid extraction. Of 96 unselected cases, 42% were positive for BRAF, 18% for RET/PTC, and 15% for RAS mutations. Morphologic features were evaluated in detail in 61 cases and 6 characteristic nuclear features and 3 additional microscopic features were assessed quantitatively. At least 4 nuclear features were found in each tumor, with nuclear pseudoinclusions being the least frequent finding in all mutation groups. BRAF mutations were associated with older patient age, typical papillary appearance or the tall cell variant, a higher rate of extrathyroidal extension, and more advanced tumor stage at presentation. RET/PTC rearrangements presented at younger age and had predominantly typical papillary histology, frequent psammoma bodies, and a high rate of lymph node metastases. Tumors with RAS mutations were exclusively the follicular variant of papillary carcinoma and correlated with significantly less prominent nuclear features and low rate of lymph node metastases. These findings demonstrate that BRAF, RET/PTC, and RAS mutations are associated with distinct microscopic, clinical, and biologic features of thyroid papillary carcinomas.

Original languageEnglish (US)
Pages (from-to)216-222
Number of pages7
JournalAmerican Journal of Surgical Pathology
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2006
Externally publishedYes

Fingerprint

Factor IX
Papillary Carcinoma
Mutation
Neoplasms
Point Mutation
Lymph Nodes
Carcinoma, Papillary, Follicular
Neoplasm Metastasis
Nucleic Acids
Histology
Thyroid Gland
Papillary Thyroid cancer

Keywords

  • BRAF
  • Nuclear features
  • RAS
  • RET/PTC
  • Thyroid papillary carcinoma

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. / Adeniran, Adebowale J.; Zhu, Zhaowen; Gandhi, Manoj; Steward, David L.; Fidler, James P.; Giordano, Thomas J.; Biddinger, Paul Williams; Nikiforov, Yuri E.

In: American Journal of Surgical Pathology, Vol. 30, No. 2, 01.02.2006, p. 216-222.

Research output: Contribution to journalArticle

Adeniran, Adebowale J. ; Zhu, Zhaowen ; Gandhi, Manoj ; Steward, David L. ; Fidler, James P. ; Giordano, Thomas J. ; Biddinger, Paul Williams ; Nikiforov, Yuri E. / Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. In: American Journal of Surgical Pathology. 2006 ; Vol. 30, No. 2. pp. 216-222.
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