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This Article Accepted manuscript (PDF) All Versions of this Article: JME-08-0063v1 41/4/195    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lin, X. Articles by Silverman, J. Search for Related Content PubMed PubMed Citation Articles by Lin, X. Articles by Silverman, J.

X Lin, Pathology, Northwestern University, Chicago, 60611, United States
S Finklestein, RedPath Integrated Pathology, Inc, Pittsburgh, United States
B Zhu, Pathology, Northwestern University, Chicago, United States
J Silverman, Pathology, Allegheny General Hospital, Pittsburgh, United States

Correspondence: Xiaoqi Lin, Email: xlin{at}northwestern.edu

Abstract

Papillary thyroid carcinoma (PTC) frequently presents as a multifocal process. To study importance of separating independent primary (IP) from intrathyroid metastatic (ITM) PTC, we examined 19 molecular markers on 42 separate tumors from 18 multifocal PTC cases. In 12/18 (66.7%) cases, including 6/12 (50%) papillary microcarcinoma cases, the same or similar profile of loss of heterozygosities (LOH) and B-RAF mutation was demonstrated, indicating that they were from the same primary and represented ITM. Different profiles of LOHs and B-RAF mutation were detected in separate tumors of 6/18 cases, indicating that they represented IP. Patients with ITM, including papillary microcarcinoma, had significantly increased lymph node metastasis. The frequencies of LOHs of 17q21, 17p13, 10q23 and 22q13 were higher in tumors with lymph node metastasis, suggesting that these LOHs may be important in increased lymph node metastasis. LOH of 9p21 was found the highest frequency in PTC (53.8%), followed by 1p36 (46.2%), 10q23 (34.6%), and 22q13 (34.6%). Papillary microcarcinoma had acquired similar genomic mutations as conventional PTC, but higher frequencies of mutations of B-RAF, 1p36, 18q and 22q13 were found in the larger PTC, suggesting that they might play a role in the aggressiveness of PTC. Different profiles of mutations were observed in conventional, follicular variant and diffuse sclerosing variant of PTC, which might influence the different morphological appearances and clinical courses. In conclusion, molecular analysis can separate multifocal IP PTC from ITM PTC, and may be more important than tumor size in predicting lymph node metastasis, aggressiveness and prognosis of PTC.