Xingyun Su1, Shitu Chen1, Kuifeng He1, Zhuochao Mao1, Jiaying Ruan1, Jie Zhou2, Xiaodong Teng2, Judy Jin3, Thomas J Fahey4, Weibin Wang5, Lisong Teng6. 1. Cancer Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 2. Department of Pathology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 3. Department of Endocrine Surgery, Cleveland Clinic, Cleveland, OH, USA. 4. Department of Surgery, New York Presbyterian Hospital and Weill Medical College of Cornell University, New York, NY, USA. 5. Cancer Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. wbwang@zju.edu.cn. 6. Cancer Center, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. lsteng@zju.edu.cn.
Abstract
INTRODUCTION: Bilaterality is a newly identified indicator for aggressive tumor behavior and poor outcome in papillary thyroid cancer. However, the clonal origin of these bilateral tumors remains unclear. METHODS: Here we analyzed 28 pairs of early-stage papillary thyroid cancers (stage I-II without extra-thyroidal extension, lymph node metastasis or distant metastasis) that underwent surgery at First Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China). Genomic DNA was extracted from paraffin-embedded tissues after microdissection and analyzed for BRAF mutation and X-chromosome inactivation. RESULTS: A total of 16 patients (16/28, 57.1%) harbored different BRAF status in bilateral tumors. Fourteen patients were available for X-chromosome inactivation assay and 10 of them achieved informative results. Bilateral tumors from four cases had distinct patterns of X-chromosome inactivation. Combining the results of X-chromosome inactivation and BRAF analysis, we demonstrated that at least 64.3% (18/28) cases harbored discordant X-chromosome inactivation or BRAF status, indicating their independent clonal origin in bilateral tumors. CONCLUSIONS: The present study confirms "field cancerization" in early-stage bilateral thyroid cancers, suggesting that these subtype papillary thyroid cancers should be treated as independent and localized tumors.
INTRODUCTION: Bilaterality is a newly identified indicator for aggressive tumor behavior and poor outcome in papillary thyroid cancer. However, the clonal origin of these bilateral tumors remains unclear. METHODS: Here we analyzed 28 pairs of early-stage papillary thyroid cancers (stage I-II without extra-thyroidal extension, lymph node metastasis or distant metastasis) that underwent surgery at First Affiliated Hospital of Zhejiang University School of Medicine (Hangzhou, China). Genomic DNA was extracted from paraffin-embedded tissues after microdissection and analyzed for BRAF mutation and X-chromosome inactivation. RESULTS: A total of 16 patients (16/28, 57.1%) harbored different BRAF status in bilateral tumors. Fourteen patients were available for X-chromosome inactivation assay and 10 of them achieved informative results. Bilateral tumors from four cases had distinct patterns of X-chromosome inactivation. Combining the results of X-chromosome inactivation and BRAF analysis, we demonstrated that at least 64.3% (18/28) cases harbored discordant X-chromosome inactivation or BRAF status, indicating their independent clonal origin in bilateral tumors. CONCLUSIONS: The present study confirms "field cancerization" in early-stage bilateral thyroid cancers, suggesting that these subtype papillary thyroid cancers should be treated as independent and localized tumors.
Entities:
Keywords:
Bilaterality; Clonal origin; Early stage; Field cancerization; Papillary thyroid cancer
Authors: Ryan P McCarthy; Mingsheng Wang; Timothy D Jones; Randall W Strate; Liang Cheng Journal: Clin Cancer Res Date: 2006-04-15 Impact factor: 12.531