title: Polo-like kinase isoforms in breast cancer: expression patterns and prognostic implications.
abstract: 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.
authors.affiliation: Institute of Pathology, Charité University Hospital, Schumannstrasse 20/21, 10117, Berlin, Germany. wilko.weichert@charite.de
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Klaus-Jürgen
authors.initials: KJ
authors.lastname: Winzer
authors.forename: Mathias
authors.initials: M
authors.lastname: Schmidt
authors.forename: Volker
authors.initials: V
authors.lastname: Gekeler
authors.forename: Aurelia
authors.initials: A
authors.lastname: Noske
authors.forename: Berit-Maria
authors.initials: BM
authors.lastname: Müller
authors.forename: Silvia
authors.initials: S
authors.lastname: Niesporek
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
mesh_terms: 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
chemical_list: 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