Talvinen K, Tuikkala J, Nevalainen O, Rantanen A, Hirsimäki P, Sundström J, Kronqvist P
Department of Pathology, Turku University Hospital, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland.
Br J Cancer. 2008 Jul 22;99(2):335-40. doi: 10.1038/sj.bjc.6604475. Epub 2008 Jul 1.
We introduce a new proliferation marker, securin (pituitary tumour-transforming 1 (PTTG1)), analysed in invasive ductal breast carcinomas by cDNA microarrays and immunohistochemistry. In cDNA microarray of a total of 4000 probes of genes, securin was revealed with a significant change in expression among the several proliferation-related genes studied. The value of securin as a proliferation marker was verified immunohistochemically (n=44) in invasive ductal breast cancer. In follow-up analyses of the sample of patients, the prognostic value of securin was compared with the established markers of breast cancer proliferation, Ki-67 and mitotic activity index (MAI). Our results of a small sample of patients suggest that low securin expression identifies a distinct subgroup of more favourable outcome among patients with high Ki-67 immunoexpression or high MAI. In univariate analysis of Cox's regression, 10-unit increment of securin immunopositivity was associated with a 2.3-fold overall risk of death due to breast cancer and a 7.1-fold risk of death due to breast cancer in the sample of patients stratified according to the cutoff points of 10 and 20% of securin immunopositivity. We suggest that securin immunostaining is a promising and clinically applicable proliferation marker. The finding urges further prognostic studies with a large sample of patients.
我们引入了一种新的增殖标志物——分离酶(垂体肿瘤转化基因1,PTTG1),通过cDNA微阵列和免疫组织化学方法对浸润性导管乳腺癌进行分析。在总共4000个基因探针的cDNA微阵列中,在所研究的几个增殖相关基因中,分离酶的表达出现了显著变化。在浸润性导管乳腺癌中通过免疫组织化学方法(n = 44)验证了分离酶作为增殖标志物的价值。在对患者样本的随访分析中,将分离酶的预后价值与已确立的乳腺癌增殖标志物Ki-67和有丝分裂活性指数(MAI)进行了比较。我们对一小部分患者的研究结果表明,在Ki-67免疫表达高或MAI高的患者中,分离酶低表达可识别出预后更有利的一个独特亚组。在Cox回归单因素分析中,根据分离酶免疫阳性率10%和20%的截断点分层的患者样本中,分离酶免疫阳性率每增加10个单位,因乳腺癌导致的总体死亡风险增加2.3倍,因乳腺癌导致的死亡风险增加7.1倍。我们认为分离酶免疫染色是一种有前景且临床适用的增殖标志物。这一发现促使对大量患者进行进一步的预后研究。