Nuclear karyopherin alpha2 expression predicts poor survival in patients with advanced breast cancer irrespective of treatment intensity.

Abstract

Intensive lymph node involvement indicates poor prognosis in breast cancer patients. The significance of other molecular prognostic factors in this subgroup is unclear. Karyopherin alpha2 (KPNA2) has been reported as an important factor of tumorgenesis and progression of breast cancer. The aim of present study was to evaluate the impact of KPNA2 expression on prognosis of patients with high risk breast cancer (HRBC) and response intensive chemotherapy within the randomized WSG-AM-01 trial. KPNA2 nuclear expression (>10% vs. <10% of nuclei) was measured by immunohistochemistry on tissue arrays of 191 patients randomized to tandem high dose vs. conventional dose-dense chemotherapy in HRBC with >9 positive lymph nodes and correlated with clinical outcome (median follow-up of 63.3 months) by Kaplan-Meier and multivariate Cox hazard model analysis, including, molecular subtypes determined by k-clustering (k = 5). KPNA2 overexpression (n = 74, 39%) significantly correlated with shorter event-free and overall survival (OS) in both therapy arms by univariate analysis. Multivariate analysis showed that the overexpression of KPNA2 was an independent prognostic factor of decreased OS HR = 1.86 [95% CI: 1.07-3.23, p = 0.03]. This predictive value was independent of basal-like/Her-2/neu subtypes, significantly associated with KPNA2 and was addressed particularly to G2 tumors. Our data suggest the use of KPNA2 nuclear expression as novel prognostic marker in node-positive patients, especially in determination of G2 tumors in 2 subgroups of different prognosis. KPNA2 expression may be also considered as a marker for global chemoresistance, which can not be overcome by conventional dose-modification of chemotherapy in advanced breast cancer.

• Authors: Oleg Gluz, Peter Wild, Robert Meiler, Raihana Diallo-Danebrock, Evelyn Ting, Svjetlana Mohrmann, Gerhart Schuett, Edgar Dahl, Thomas Fuchs, Alexander Herr, Andreas Gaumann, Markus Frick, Christopher Poremba, Ulrike Anneliese Nitz, Arndt Hartmann
• Journal: International journal of cancer (Int J Cancer) Vol. 123 Issue 6 Pg. 1433-8 (Sep 15 2008) ISSN: 1097-0215 [Electronic] United States
• PMID: 18561322 (Publication Type: Journal Article)
• Copyright: Copyright 2008 Wiley-Liss, Inc.

Chemical References

• Biomarkers, Tumor
• KPNA2 protein, human
• alpha Karyopherins
• Receptor, ErbB-2

Topics

• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Biomarkers, Tumor (analysis)
• Breast Neoplasms (drug therapy, metabolism, mortality)
• Cell Nucleus (metabolism)
• Dose-Response Relationship, Drug
• Female
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Lymphatic Metastasis (pathology)
• Middle Aged
• Prognosis
• Randomized Controlled Trials as Topic
• Receptor, ErbB-2 (genetics, metabolism)
• Tissue Array Analysis
• alpha Karyopherins (biosynthesis)