Polo-like kinase isoforms in breast cancer: expression patterns and prognostic implications.
Polo-like kinase (PLK) family members are known to be functionally involved in mitotic signaling and in cytoskeletal reorganization in both normal and malignant cells. In this study, expression of PLK1 and PLK3 was determined immunohistochemically in tissue specimens of 135 breast carcinomas, and expression was correlated with clinicopathological parameters and patient prognosis. Strong PLK isoform overexpression was observed in 42.2% (PLK1) and 47.4% (PLK3) of breast carcinomas when compared with non-transformed breast tissue. A positive correlation of PLK isoform expression with tumor grade, vascular invasion, erbB2/HER-2 expression and markers of proliferative activity was evident. Additionally, an inverse correlation of PLK isoform expression and estrogen receptor status was observed. Overexpression of PLK3 but not of PLK1 was significantly linked to reduced median overall (P<0.001) and relapse-free (P=0.021) survival time. PLK3 expression remained an independent prognostic factor for overall (RR=3.2, P=0.002) and relapse-free (RR=2.9, P=0.049) survival in multivariate survival analysis. These results suggest PLK3 as a novel independent prognostic marker in breast cancer and hint toward a role for PLK isoform overexpression in disease progression. Therefore, in vivo inhibition of PLK family members might represent a rewarding approach in the development of new anticancer drugs for this tumor entity.
Weichert
Wilko
W
Institute of Pathology, Charité University Hospital, Schumannstrasse 20/21, 10117, Berlin, Germany. wilko.weichert@charite.de
Kristiansen
Glen
G
Winzer
Klaus-Jürgen
KJ
Schmidt
Mathias
M
Gekeler
Volker
V
Noske
Aurelia
A
Müller
Berit-Maria
BM
Niesporek
Silvia
S
Dietel
Manfred
M
Denkert
Carsten
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000201:enzymology / Q000401:mortality / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016019:Survival Analysis; D015996:Survival Rate; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; D000097868:Polo-like Kinases
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D007527:Isoenzymes; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; C486256:PLK3 protein, human; D000097868:Polo-like Kinases