Heeran Mel C, Rask Lene, Høgdall Claus K, Kjaer Susanne K, Christensen Lise, Jensen Allan, Blaakaer Jan, Jarle Christensen I B, Høgdall Estrid V S
Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark; Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
APMIS. 2015 May;123(5):401-9. doi: 10.1111/apm.12368. Epub 2015 Apr 4.
The primary objective of this study was to analyse Tetranectin (TN) expression in tumour tissues and TN serum concentration in 758 women with epithelial ovarian tumours. The second was to evaluate, whether TN tissue expression levels correlate with clinico-pathological parameters and prognosis of the disease. Using tissue arrays we analysed the expression levels in tissues from 166 women with borderline ovarian tumours (BOTs) and 592 women with ovarian cancer (OC). A panel of three antibodies was used for immunohistochemistry: a polyclonal and two monoclonal antibodies. Serum TN was measured using the polyclonal antibody A-371. Univariate survival analyses stratified for chemotherapy showed that positive tissue TN as demonstrated by the polyclonal antibody indicated a significantly longer overall survival (OS) (p = 0.0001) as well as cancer specific survival (CSS) (p < 0.0001). High serum TN was likewise found to imply longer OS (p < 0.0001) and CSS (p < 0.0001), whereas tissue staining with the two monoclonal antibodies failed to demonstrate any significant correlation with either survival type. Univariate Kaplan-Meier survival analysis performed on all OC cases showed a significantly longer OS (p = 0.0009) and CSS (p = 0.0006) for women with TN positive tumour tissue and in women with high serum TN levels (p < 0.0001 for both). However, in the multivariate Cox regression analysis, only serum TN was found to be an independent prognostic factor for OS (p = 0.01) and not for CSS (p = 0.08). In conclusion, our results predict that a positive TN expression of both tumour tissue and serum points to a more favourable outcome for OC patients.
本研究的主要目的是分析758例上皮性卵巢肿瘤女性患者肿瘤组织中的纤连蛋白(TN)表达及血清TN浓度。其次是评估TN组织表达水平是否与疾病的临床病理参数及预后相关。我们使用组织芯片分析了166例卵巢交界性肿瘤(BOT)患者和592例卵巢癌(OC)患者组织中的表达水平。免疫组化使用了一组三种抗体:一种多克隆抗体和两种单克隆抗体。血清TN使用多克隆抗体A - 371进行检测。化疗分层的单因素生存分析显示,多克隆抗体检测出的组织TN阳性表明总生存期(OS)显著延长(p = 0.0001)以及癌症特异性生存期(CSS)显著延长(p < 0.0001)。同样发现高血清TN意味着更长的OS(p < 0.0001)和CSS(p < 0.0001),而两种单克隆抗体的组织染色未能显示与任何一种生存类型有显著相关性。对所有OC病例进行的单因素Kaplan - Meier生存分析显示,TN阳性肿瘤组织的女性患者和血清TN水平高的女性患者的OS(p = 0.0009)和CSS(p = 0.0006)显著更长(两者p均< 0.0001)。然而,在多因素Cox回归分析中,仅发现血清TN是OS的独立预后因素(p = 0.01),而不是CSS的独立预后因素(p = 0.08)。总之,我们的结果预测肿瘤组织和血清中TN表达阳性表明OC患者有更有利的预后。