Molecular analysis of multifocal papillary thyroid carcinoma.
Papillary thyroid carcinoma (PTC) frequently presents as a multifocal process. To study the 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 of 18 (66.7%) cases, including 6 of 12 (50%) papillary microcarcinoma cases, the same or similar profile of loss of heterozygosities (LOH) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation was demonstrated, indicating that they were from the same primary and represented ITM. Different profiles of LOHs and BRAF mutation were detected in separate tumors of 6 of 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 at 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 BRAF, 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 variants, 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.
Lin
Xiaoqi
X
Department of Pathology, Feinberg School of Medicine, Northwestern Memorial Hospital, Northwestern University, 251 East Huron Street, Feinberg Building 7-209C, Chicago, Illinois 60611, USA. xlin@northwestern.edu
Finkelstein
Sydney D
SD
Zhu
Bing
B
Silverman
Jan F
JF
D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002879:Chromosomes, Human, Pair 10; D002886:Chromosomes, Human, Pair 17; D002892:Chromosomes, Human, Pair 22; D004252:DNA Mutational Analysis; D018740:Genetic Heterogeneity; D006801:Humans; D019656:Loss of Heterozygosity; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf