The V109G polymorphism of the p27 gene CDKN1B indicates a worse outcome in node-negative breast cancer patients.
Although p27 plays a central role in cell cycle regulation, its role in breast cancer prognosis is controversial. Furthermore, the p27 gene CDKN1B carries a polymorphism with unknown functional relevance. This study was designed to evaluate p27 expression and p27 genotyping with respect to early breast cancer prognosis. 279 patients with infiltrating metastasis-free breast cancer were included in this study. p27 expression was determined in tumor tissue specimens from 261 patients by immunohistochemistry. From 108 patients, the CDKN1B genotype was examined by PCR and subsequent direct sequencing. 55.2% of the tumors were considered p27 positive. p27 expression did not correlate with any of the established parameters except for nodal involvement but significantly correlated to prolonged disease-free survival. In 35% of the tumors analyzed, the CDKN1B gene showed a polymorphism at codon 109 (V109G). The V109G polymorphism correlated with greater nodal involvement. In the node-negative subgroup, V109G correlated significantly with a shortened disease-free survival. In conclusion, the determination of the CDKN1B genotype might be a powerful tool for the prognosis of patients with early breast cancer.
Schöndorf
Thomas
T
Department of Natural Sciences, University of Applied Sciences Bonn-Rhein-Sieg, DE-53359 Rheinbach, Germany. thomas.schoendorf@fh-bonn-rhein-sieg.de
Eisele
Lewin
L
Göhring
Uwe-Jochen
UJ
Valter
Markus M
MM
Warm
Mathias
M
Mallmann
Peter
P
Becker
Martina
M
Fechteler
Roland
R
Weisshaar
Maria-Paz
MP
Hoopmann
Markus
M
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002453:Cell Cycle; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D012189:Retrospective Studies
C436291:CDKN1B protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27