BRAF in papillary thyroid carcinoma of ovary (struma ovarii)

Jason Schmidt, Victoria Derr, Michael Heinrich, Christopher P. Crum, Jonathan A. Fletcher, Christopher Corless, Vânia Nosé

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

BACKGROUND: Malignant struma ovarii (MSO) are rare tumors that arise from ectopic thyroid tissue in the ovary, benign struma ovarii (BSO). Most MSO are histologically classified as papillary thyroid carcinomas (PTC). Oncogenic activation of BRAF (35% to 69%), RAS (10%), or RET (5% to 30%) is common in PTC, and the mutations correlate with tumor subtype, patient age, and clinical behavior. In this study, we explored the possible role of these genes in the development of BSO and MSO. DESIGN: Six paraffin-embedded cases of MSO with histopathologic features of PTC (4 follicular variants, 1 classic, and 1 metastasis of a classic) and 9 BSO were identified. BRAF, NRAS, and KRAS mutations were evaluated using a combination of polymerase chain reaction, denaturing high performance liquid chromatography, and automated sequencing. RET alterations were screened by fluorescence in situ hybridization with multicolor probes. Corresponding benign tissues were evaluated when available. RESULTS: BRAF mutations were present in 4 of 6 MSO and none of 9 BSO. The BRAF mutations included V600E (2 cases), K601E, and a novel deletion/substitution TV599-600M. Neither MSO nor BSO contained alterations in NRAS, KRAS, or RET. CONCLUSIONS: The development of MSOs with PTC features is associated with BRAF mutations of the type commonly observed in PTC, suggesting a common pathogenesis for all PTCs regardless of location. In contrast, mutations in the RET/RAS/RAF pathway are not found in BSO. The prognostic significance of BRAF mutation status in MSO remains to be determined.

Original languageEnglish (US)
Pages (from-to)1337-1343
Number of pages7
JournalAmerican Journal of Surgical Pathology
Volume31
Issue number9
DOIs
StatePublished - Sep 2007

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Struma Ovarii
Ovary
Mutation
Papillary Thyroid cancer
Thyroid Dysgenesis
Choristoma
Factor IX

Keywords

  • BRAF
  • Malignant struma ovarii
  • Papillary thyroid carcinoma
  • RAS
  • RET

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

Cite this

BRAF in papillary thyroid carcinoma of ovary (struma ovarii). / Schmidt, Jason; Derr, Victoria; Heinrich, Michael; Crum, Christopher P.; Fletcher, Jonathan A.; Corless, Christopher; Nosé, Vânia.

In: American Journal of Surgical Pathology, Vol. 31, No. 9, 09.2007, p. 1337-1343.

Research output: Contribution to journalArticle

Schmidt, Jason ; Derr, Victoria ; Heinrich, Michael ; Crum, Christopher P. ; Fletcher, Jonathan A. ; Corless, Christopher ; Nosé, Vânia. / BRAF in papillary thyroid carcinoma of ovary (struma ovarii). In: American Journal of Surgical Pathology. 2007 ; Vol. 31, No. 9. pp. 1337-1343.
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abstract = "BACKGROUND: Malignant struma ovarii (MSO) are rare tumors that arise from ectopic thyroid tissue in the ovary, benign struma ovarii (BSO). Most MSO are histologically classified as papillary thyroid carcinomas (PTC). Oncogenic activation of BRAF (35{\%} to 69{\%}), RAS (10{\%}), or RET (5{\%} to 30{\%}) is common in PTC, and the mutations correlate with tumor subtype, patient age, and clinical behavior. In this study, we explored the possible role of these genes in the development of BSO and MSO. DESIGN: Six paraffin-embedded cases of MSO with histopathologic features of PTC (4 follicular variants, 1 classic, and 1 metastasis of a classic) and 9 BSO were identified. BRAF, NRAS, and KRAS mutations were evaluated using a combination of polymerase chain reaction, denaturing high performance liquid chromatography, and automated sequencing. RET alterations were screened by fluorescence in situ hybridization with multicolor probes. Corresponding benign tissues were evaluated when available. RESULTS: BRAF mutations were present in 4 of 6 MSO and none of 9 BSO. The BRAF mutations included V600E (2 cases), K601E, and a novel deletion/substitution TV599-600M. Neither MSO nor BSO contained alterations in NRAS, KRAS, or RET. CONCLUSIONS: The development of MSOs with PTC features is associated with BRAF mutations of the type commonly observed in PTC, suggesting a common pathogenesis for all PTCs regardless of location. In contrast, mutations in the RET/RAS/RAF pathway are not found in BSO. The prognostic significance of BRAF mutation status in MSO remains to be determined.",
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