Abstract
The aim of this study was to evaluate protein expression of Karyopherin alpha 2 (KPNA2) in invasive breast cancer and matched ductal carcinoma in situ (DCIS) and to correlate it with clinicopathological data, including patient survival. KPNA2 protein expression was assessed by immunohistochemistry in breast tissue samples, containing invasive carcinomas, DCIS, and adjacent histologically benign breast tissues. A polyclonal goat KPNA2 antibody was used for immunostaining of 83 clinicopathologically characterized cases. For statistical analysis, staining of at least 10% of nuclei was considered KPNA2 positive. Immunohistochemical detection of KPNA2 in invasive carcinoma showed a significant correlation with higher tumor stage, positive lymph node status, higher tumor grade, and negative ER status. Concordantly, KPNA2-positive tumors (31.3%) showed significantly shorter disease-free survival times (69 months vs 118 months; p = 0.007). KPNA2 protein expression was also detected in DCIS (21.3%) adjacent to invasive tumor and correlated with nuclear grade (p = 0.013). Expression of KPNA2 in invasive breast cancer correlates with conventional prognostic parameters and shorter disease-free survival. Additionally, KPNA2 is overexpressed in DCIS, particularly high grade lesions, which emphasizes its potential role in carcinogenesis of invasive breast carcinomas.
MeSH Terms
Adult
Aged
Aged, 80 and over
Breast Neoplasms/metabolism
Carcinoma in Situ/pathology
Carcinoma, Ductal, Breast/pathology
Female
Humans
Immunohistochemistry
Middle Aged
Prognosis
Survival Analysis
alpha Karyopherins/biosynthesis
Chemicals
alpha Karyopherins
karyopherin alpha 2
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Dankof Anja
Institute of Pathology, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Charitéplatz 1, 10098 Berlin, Germany.
Fritzsche Florian R
Dahl Edgar
Pahl Stefan
Wild Peter
Dietel Manfred
Hartmann Arndt
Kristiansen Glen
References (20)
20 references, click to expand
-
High Ep-CAM expression is associated with poor prognosis in node-positive breast cancer.
Breast Cancer Res Treat. 2004 Aug;86(3):207-13
PMID: 15567937
-
Human kallikrein gene 5 (KLK5) expression by quantitative PCR: an independent indicator of poor prognosis in breast cancer.
Clin Chem. 2002 Aug;48(8):1241-50
PMID: 12142380
-
Truncated form of importin alpha identified in breast cancer cell inhibits nuclear import of p53.
J Biol Chem. 2000 Jul 28;275(30):23139-45
PMID: 10930427
-
Comparison of gene expression data from human and mouse breast cancers: identification of a conserved breast tumor gene set.
Int J Cancer. 2007 Aug 1;121(3):683-8
PMID: 17410534
-
Enhanced mRNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in breast carcinomas is correlated with adverse prognosis.
J Pathol. 2002 Jul;197(3):307-13
PMID: 12115876
-
Regulation of nuclear transport: central role in development and transformation?
Traffic. 2005 Mar;6(3):173-86
PMID: 15702986
-
Loss of SFRP1 is associated with breast cancer progression and poor prognosis in early stage tumors.
Int J Oncol. 2004 Sep;25(3):641-9
PMID: 15289865
-
Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up.
Histopathology. 1991 Nov;19(5):403-10
PMID: 1757079
-
Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1.
Ann Oncol. 2006 Apr;17(4):597-604
PMID: 16403812
-
High survivin predicts a poor response to endocrine therapy, but a good response to chemotherapy in advanced breast cancer.
Breast Cancer Res Treat. 2006 Jul;98(2):223-30
PMID: 16541327
-
Localization of BRCA1 and a splice variant identifies the nuclear localization signal.
Mol Cell Biol. 1997 Jan;17(1):444-52
PMID: 8972225
-
CD24 expression is a new prognostic marker in breast cancer.
Clin Cancer Res. 2003 Oct 15;9(13):4906-13
PMID: 14581365
-
Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer.
Cancer Res. 2002 Jun 15;62(12):3417-27
PMID: 12067984
-
Complex of urokinase-type plasminogen activator with its type 1 inhibitor predicts poor outcome in 576 patients with lymph node-negative breast carcinoma.
Cancer. 2004 Aug 1;101(3):486-94
PMID: 15274061
-
Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer.
Lancet. 2005 Feb 19-25;365(9460):671-9
PMID: 15721472
-
TNM Classification of Malignant Tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer.
Cancer. 1997 Nov 1;80(9):1803-4
PMID: 9351551
-
Karyopherins and nuclear import.
Curr Opin Struct Biol. 2001 Dec;11(6):703-15
PMID: 11751052
-
Molecular profiling of laser-microdissected matched tumor and normal breast tissue identifies karyopherin alpha2 as a potential novel prognostic marker in breast cancer.
Clin Cancer Res. 2006 Jul 1;12(13):3950-60
PMID: 16818692
-
Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis.
J Natl Cancer Inst. 2006 Feb 15;98(4):262-72
PMID: 16478745
-
Cancer statistics, 2007.
CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66
PMID: 17237035