Weichert W, Denkert C, Schmidt M, Gekeler V, Wolf G, Köbel M, Dietel M, Hauptmann S
Institute of Pathology, Charité Hospital, Humboldt University, Schumannstrasse 20/21, Berlin 10117, Germany.
Br J Cancer. 2004 Feb 23;90(4):815-21. doi: 10.1038/sj.bjc.6601610.
The Polo-like kinase (PLK) family comprises three serine/threonine kinases, functionally involved in signal transduction pathways essential for the accomplishment of mitosis in both normal and malignant cells. Moreover, certain PLKs have been functionally linked to cytoskeletal reorganisation. In this study, the expression of PLK1 and PLK3 was determined immunohistochemically in tissue specimen of normal ovaries (n=9), cystadenomas (n=17), borderline tumours (n=13) and ovarian carcinomas (n=77). PLK 1 and PLK3 expression was low in normal ovarian surface epithelium and borderline tumours, with moderately higher expression levels in cystadenomas. In ovarian carcinomas, 26% of cases were PLK1 positive and 50.6% of cases were PLK3 positive. A positive correlation of both PLK1 and PLK3 expression with indicators of mitotic frequency could be established. The overexpression of either isoenzyme had an impact on patient prognosis with shortened survival time for patients with tumours positive for PLK1 (P=0.02) and PLK3 (P=0.02), but only PLK1 expression remained a prognostic factor in multivariate survival analysis (P=0.03). The results of this study, if interpreted in the context of recently published functional data, suggest that inhibition of PLKs might represent an interesting new targeted approach for chemotherapy of epithelial ovarian cancer. Furthermore, this study suggests that PLK1 is a novel independent prognostic marker in ovarian carcinomas.
Polo样激酶(PLK)家族由三种丝氨酸/苏氨酸激酶组成,在正常细胞和恶性细胞完成有丝分裂所必需的信号转导途径中发挥功能作用。此外,某些PLK与细胞骨架重组存在功能联系。在本研究中,采用免疫组织化学方法检测了正常卵巢组织标本(n = 9)、囊腺瘤(n = 17)、交界性肿瘤(n = 13)和卵巢癌(n = 77)中PLK1和PLK3的表达。PLK 1和PLK3在正常卵巢表面上皮和交界性肿瘤中的表达较低,在囊腺瘤中的表达水平略高。在卵巢癌中,26%的病例PLK1呈阳性,50.6%的病例PLK3呈阳性。PLK1和PLK3的表达与有丝分裂频率指标均呈正相关。两种同工酶的过表达均对患者预后有影响,PLK1阳性(P = 0.02)和PLK3阳性(P = 0.02)的肿瘤患者生存时间缩短,但在多因素生存分析中只有PLK1表达仍然是一个预后因素(P = 0.03)。如果结合最近发表的功能数据来解释本研究结果,提示抑制PLK可能是上皮性卵巢癌化疗一种有趣的新靶向方法。此外,本研究提示PLK1是卵巢癌一种新的独立预后标志物。