BRAFV600E Mutation and p27kip1 Expression in Papillary Carcinomas of the Thyroid ≤1 cm and Their Paired Lymph Node Metastases

BACKGROUND. BRAFV600E mutation and p27kip1 expression have been introduced as novel indicators that may predict prognosis in different tumors, as well as in papillary thyroid carcinomas. METHODS. Tissue samples from 214 consecutive patients who underwent total or near-total thyroidectomy with histological diagnosis of papillary thyroid carcinoma (PTC) ≤1 cm were analyzed for BRAFV600E mutation by a real-time, allele-specific amplification and for p27kip1 expression by immunohistochemistry. RESULTS. The BRAFV600E mutation was detected in 88 of the tumors examined, with significant differences between groups with and without lymph node (LN) metastases; the mean age of patients with BRAFV600E mutation was significantly higher than that of patients without mutations. A significant association was found between low p27Kip1 protein expression and multifocality, bilaterality, and extrathyroidal extension, in addition to LN metastasis. In 42 cases with LN metastases, 23 harbored the BRAFV600E mutation in the metastatic tumor and presented a wider diameter of the largest metastatic area, a higher number of involved LNs, and a higher percentage of metastatic lesions with extracapsular extension of LN (ECE-LN). A significantly lower mean value of p27Kip1 was observed in LNs harboring the BRAFV600E mutation and in ECE-LN; an inverse correlation was found between p27Kip1 and the number of metastatic LNs, as well as the diameter of the largest metastatic area in LN. CONCLUSIONS. The authors' data suggested that BRAFV600E mutation and p27Kip1 down-regulation in cancer cells of PTC ≤1 cm may be factors that facilitate tumor-cell growth and progression once these are seeded in the LNs. Cancer 2007. © 2007 American Cancer Society.