Molecular analysis of multifocal papillary thyroid carcinoma

Abstract

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.

Predictive Factors for Incidental Contralateral Carcinoma in Patients with Unilateral Micropapillary Thyroid Carcinoma

“…But other studies reported that there was no significant association between multifocality and LN metastasis or recurrence [17]. One explanation for this observation is that multifocality most often is the result of the development of multiple independent tumors and not a manifestation of intraglandular dissemination, as demonstrated by recent molecular investigations of multifocal PTC [17][18][19][20]. Each of the different microtumors seems to have the limited growth potential.…”

Clinical Workup of Nodular and Mass Lesions of the Endocrine Organs

“…Follicular adenomas and Hürthle cell adenomas have similar gene expression profile as malignant tumors (Arora, Scognamiglio et al 2008). By detection of BRAF mutation and loss of heterozygosities (LOH), 66.7% papillary thyroid carcinomas (PTC), including 50% papillary microcarcinoma cases (<1 cm), were proved to be intrathyroid metastasis (Lin, Finkelstein et al 2008). Patients with intrathyroid metastasis, including papillary microcarcinoma, had significantly increased lymph node metastasis (Lin, Finkelstein et al 2008).…”

“…By detection of BRAF mutation and loss of heterozygosities (LOH), 66.7% papillary thyroid carcinomas (PTC), including 50% papillary microcarcinoma cases (<1 cm), were proved to be intrathyroid metastasis (Lin, Finkelstein et al 2008). Patients with intrathyroid metastasis, including papillary microcarcinoma, had significantly increased lymph node metastasis (Lin, Finkelstein et al 2008). LOHs of 17q21, 17p13, 10q23 and 22q13 may be important in predicting increased risk of lymph node metastasis (Lin, Finkelstein et al 2008).…”

“…Patients with intrathyroid metastasis, including papillary microcarcinoma, had significantly increased lymph node metastasis (Lin, Finkelstein et al 2008). LOHs of 17q21, 17p13, 10q23 and 22q13 may be important in predicting increased risk of lymph node metastasis (Lin, Finkelstein et al 2008). 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%) (Lin, Finkelstein et al 2008).…”

“…LOHs of 17q21, 17p13, 10q23 and 22q13 may be important in predicting increased risk of lymph node metastasis (Lin, Finkelstein et al 2008). 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%) (Lin, Finkelstein et al 2008). Papillary microcarcinoma had acquired similar genomic mutations as conventional PTC (>1 cm), 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 (Lin, Finkelstein et al 2008).…”