Analysis of differential BRAF(V600E) mutational status in multifocal papillary thyroid carcinoma: evidence of independent clonal origin in distinct tumor foci.
BACKGROUND
Papillary thyroid cancers often occur as multiple foci. Multifocal cancers have been considered to have a poor prognosis because they are thought to be the consequence of intrathyroidal spread of the papillary cancer. However, to the authors' knowledge there has been little investigation into whether multifocal thyroid papillary carcinomas arise from the intrathyroidal spread of a single carcinoma or from independent primary tumors. To answer this question, the BRAF(V600E) mutational status of individual tumor foci was examined. This approach was justified because in the Korean population a high proportion (65%) of papillary carcinomas harbor the BRAF mutation.


METHODS
DNA was isolated from paraffin-embedded tissue samples of multifocal papillary thyroid carcinoma and the BRAF exon 15 was amplified by the polymerase chain reaction (PCR). The PCR product was digested with restriction endonuclease TspRI to test for the presence of the BRAF(V600E) (T1799A) mutation.


RESULTS
In all, 140 cancers from 61 patients diagnosed with multifocal papillary carcinoma were examined. The BRAF mutation was found in all the individual cancers in 29 (47.5%) of the patients (all-positive group) and the mutation was absent in all the individual cancers in 8 (13.1%) patients (all-negative group). However, in 24 (39.3%) patients, some of the individual cancers contained the BRAF mutation, whereas others did not (mixed group).


CONCLUSIONS
At least 39.3% of the multifocal papillary cancers in the Korean population that were examined could be attributed to independently arising papillary cancers rather than to intrathyroidal spread of single cancers.
Park
So Yeon
SY
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.
Park
Young Joo
YJ
Lee
Yu Jin
YJ
Lee
Hyun Sook
HS
Choi
Sung Hee
SH
Choe
Gheeyoung
G
Jang
Hak-Chul
HC
Park
Seong Hoe
SH
Park
Do Joon
DJ
Cho
Bo Youn
BY
D000328:Adult; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf