Clonal analysis of bilateral, recurrent, and metastatic papillary thyroid carcinomas.
Papillary thyroid carcinoma usually presents as a multifocal disease; and tumors often recur in the contralateral thyroid lobe, raising questions concerning their clonal origins. The clonality of tumors appearing simultaneously in both lobes or recurring in the contralateral lobe remains unknown. Accordingly, we examined 25 pairs of bilateral papillary thyroid carcinomas (synchronous or metachronous) and 15 matched metastatic lymph nodes. BRAF gene mutation analysis combined with X-chromosome inactivation was used to evaluate these tumors' clonal origins. Genomic DNA was prepared from paraffin-embedded tissues after microdissection. In total, 62 tumors yielded DNA of adequate quality. Eighteen (18/21, 85.7%) of 21 informative cases showed concordant BRAF status in tumors from both thyroid lobes, being either BRAF mutation positive (12 patients) or BRAF mutation negative (6 patients). Metastatic lymph nodes in 12 patients (12/15, 80%) had a complete concordance of BRAF state with their primaries. Of the 18 studied female patients, 11 were suitable for X-chromosome inactivation assay. Nine cases (9/11, 81.1%) showed the same pattern of inactivation in bilateral tumors. A close correlation was found between BRAF mutation and X-chromosome inactivation analysis. In conclusion, our data provide evidence that bilateral, recurrent, and metastatic papillary thyroid carcinomas often arise from a single clone and that intrathyroidal metastasis may play an important role in the development of bilateral tumors, as well as in the recurrence of this malignancy.
Wang
Weibin
W
Cancer Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Wang
Haiyong
H
Teng
Xiaodong
X
Wang
Haohao
H
Mao
Chenyu
C
Teng
Rongyue
R
Zhao
Wenhe
W
Cao
Jiang
J
Fahey
Thomas J
TJ
Teng
Lisong
L
D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000556:secondary* / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D041321:Chromosomes, Human, X / Q000235:genetics; D002999:Clone Cells; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology*; D009367:Neoplasm Staging; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D013965:Thyroidectomy; D049951:X Chromosome Inactivation / Q000235:genetics; D055815:Young Adult
D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf