BRAF V600E mutation and p27 kip1 expression in papillary carcinomas of the thyroid <or=1 cm and their paired lymph node metastases.
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.
Department of Human Pathology, University of Palermo, Palermo, Italy. rodolico@unipa.it
Vito
V
Rodolico
Daniela
D
Cabibi
Giuseppe
G
Pizzolanti
Pierina
P
Richiusa
Nicola
N
Gebbia
Anna
A
Martorana
Antonio
A
Russo
Marco C
MC
Amato
Aldo
A
Galluzzo
Carla
C
Giordano
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D002291:Carcinoma, Papillary / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018698:Glutamic Acid; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D014633:Valine
D014408:Biomarkers, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018698:Glutamic Acid; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine