BRAF V600E mutation and p27 kip1 expression in papillary carcinomas of the thyroid Vito Rodolico 1 , Daniela Cabibi, Giuseppe Pizzolanti, Pierina Richiusa, Nicola Gebbia, Anna Martorana, Antonio Russo, Marco C Amato, Aldo Galluzzo, Carla Giordano Affiliations Expand Affiliation 1 Department of Human Pathology, University of Palermo, Palermo, Italy. rodolico@unipa.it PMID: 17685465 DOI: 10.1002/cncr.22912 Free article Item in Clipboard
Vito Rodolico, Daniela Cabibi, Giuseppe Pizzolanti, Pierina Richiusa, Nicola Gebbia, Anna Martorana, Antonio Russo, Marco C Amato, Aldo Galluzzo, Carla Giordano, Vito Rodolico, Daniela Cabibi, Giuseppe Pizzolanti, Pierina Richiusa, Nicola Gebbia, Anna Martorana, Antonio Russo, Marco C Amato, Aldo Galluzzo, Carla Giordano
Abstract
Background: BRAF(V600E) mutation and p27(kip1) 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) <or=1 cm were analyzed for BRAF(V600E) mutation by a real-time, allele-specific amplification and for p27(kip1) expression by immunohistochemistry.
Results: The BRAF(V600E) 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 BRAF(V600E) mutation was significantly higher than that of patients without mutations. A significant association was found between low p27(Kip1) protein expression and multifocality, bilaterality, and extrathyroidal extension, in addition to LN metastasis. In 42 cases with LN metastases, 23 harbored the BRAF(V600E) 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 p27(Kip1) was observed in LNs harboring the BRAF(V600E) mutation and in ECE-LN; an inverse correlation was found between p27(Kip1) and the number of metastatic LNs, as well as the diameter of the largest metastatic area in LN.
Conclusions: The authors' data suggested that BRAF(V600E) mutation and p27(Kip1) down-regulation in cancer cells of PTC <or=1 cm may be factors that facilitate tumor-cell growth and progression once these are seeded in the LNs.
(c) 2007 American Cancer Society.
Source: PubMed