Clonal analysis of bilateral, recurrent, and metastatic papillary thyroid carcinomas.

Area of Science:

• Oncology
• Genetics
• Endocrinology

Background:

• Papillary thyroid carcinoma frequently presents as multifocal disease.
• Tumor recurrence in the contralateral lobe raises questions about clonal origins.
• The clonality of synchronous or metachronous bilateral tumors is not well understood.

Purpose of the Study:

• To investigate the clonal origins of bilateral papillary thyroid carcinomas.
• To determine if bilateral tumors and metastatic lymph nodes arise from a single clone.
• To correlate BRAF mutation status and X-chromosome inactivation patterns.

Main Methods:

• Analysis of BRAF gene mutation status in bilateral tumors.
• X-chromosome inactivation assay on tumor samples from female patients.
• Microdissection and DNA extraction from paraffin-embedded tissues.
• Examination of 25 pairs of bilateral tumors and 15 matched lymph nodes.

Main Results:

• 85.7% of informative cases showed concordant BRAF status between bilateral tumors.
• 80% of metastatic lymph nodes had concordant BRAF status with primary tumors.
• 81.1% of suitable female patients exhibited identical X-chromosome inactivation patterns in bilateral tumors.
• Strong correlation observed between BRAF mutation and X-chromosome inactivation analyses.

Conclusions:

• Bilateral, recurrent, and metastatic papillary thyroid carcinomas frequently originate from a single clone.
• Intrathyroidal metastasis is a significant factor in the development of bilateral tumors.
• Findings support a common clonal origin for multifocal and recurrent thyroid cancers.