BRAF in papillary thyroid carcinoma of ovary (struma ovarii).
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.


METHODS
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.
Schmidt
Jason
J
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. jschmidt@partners.org
Derr
Victoria
V
Heinrich
Michael C
MC
Crum
Christopher P
CP
Fletcher
Jonathan A
JA
Corless
Christopher L
CL
Nosé
Vânia
V
D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D013330:Struma Ovarii / Q000235:genetics* / Q000473:pathology
D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf