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- Title
Multicentric occurrence of multiple papillary thyroid carcinomas - HUMARA and BRAF mutation analysis.
- Authors
Nakazawa, Tadao; Kondo, Tetsuo; Tahara, Ippei; Kasai, Kazunari; Inoue, Tomohiro; Oishi, Naoki; Mochizuki, Kunio; Kubota, Takeo; Katoh, Ryohei
- Abstract
Papillary thyroid carcinomas ( PTCs) occasionally form multiple tumor foci in different sites of the same thyroid gland. However, it is controversial whether discrete nodules of PTC arise independently (multicentric occurrence) or are seeded from a single tumor via lymphatic channels (intraglandular metastasis). In order to determine the clonal origin of multiple PTCs, we examined X-chromosome inactivation patterns using a human androgen receptor gene-based assay ( HUMARA) and the BRAF mutation using allele-specific PCR ( AS- PCR) in 32 microdissected cancerous tissues from 14 Japanese women with multifocal PTC. All tumor foci were greater than 3 mm in size and met the criteria for microscopic classical PTC. Samples from 13 of the 14 patients were informative based on HUMARA. Tumor foci from two cases (15.4%) displayed a discordant X-chromosome inactivation pattern. Foci from the other 11 cases (84.6%) showed a concordant inactivation pattern of the X-chromosome. AS- PCR indicated that BRAF mutational status between the tumor foci was discordant in three (25%) and concordant in nine (75%) of 12 available cases. When the results of these two molecular analyses were combined, 28.6% of the cases were discordant in X-chromosome inactivation pattern and/or BRAF mutation, suggesting multicentric origin. Some of the remaining concordant cases also may be of multicentric origin. These results support a hypothesis that multicentric occurrence in multiple PTCs may be common, possibly greater than 30%. Although the exact mechanism of multicentric occurrence is still unclear, our findings contribute to the understanding the histogenesis of papillary thyroid carcinoma.
- Subjects
BRAF genes; METASTASIS; PAPILLARY carcinoma; X chromosome; ANDROGEN receptors
- Publication
Cancer Medicine, 2015, Vol 4, Issue 8, p1272
- ISSN
2045-7634
- Publication type
Article
- DOI
10.1002/cam4.466