Abstract:
Survivin was previously associated with tumor stage and grade in ovarian cancer and interfered with the tumor\'s drug sensitivity. In addition, Survivin expression was found to be regulated by the Sonic hedgehog (Shh) pathway, Krüppel-like factor (KLF) family proteins, and p53 pathway. The main aim of this study was to assess the prognostic values of immunohistochemical expression of Survivin, Klf5, Klf11, Shh, p53, p21, and Mdm2 in a cohort of high-grade ovarian serous cancers. Other aims were comparison between high- and low-grade ovarian serous cancer and between platinum-resistant and the other cases. The last aim was to assess the correlations among the immunohistochemical expression of the studied proteins. Retrospective cohort study to assess immunohistochemical expression of Survivin, Klf5, Klf11, Shh, p53, p21, and Mdm2 in a tissue microarray of primary tumor samples among 73 women affected by high-grade ovarian serous cancer and 9 by low-grade ovarian serous cancer. Klf5 and Shh cytoplasmic staining were associated with short overall survival (HR 6.38, 95% CI 2.25-18.01, P < .05 and 2.25, 95% CI 1.19-4.23, P < .05, respectively). In addition, cytoplasmic Klf5 staining, high Klf11, and p53 nuclear staining were associated with platinum resistance (P < .05). Cytoplasmic Shh score was significantly correlated to the immunohistochemical expression of Klf5, Klf11, Mdm2, and Survivin. Our data highlight the possible role of Klf5 and Shh as prognostic markers, meanwhile confirming the role of the KLF family proteins and p53 in ovarian cancer drug resistance. Moreover, Shh appeared to play an important role in the intracellular network of ovarian neoplasia.
摘要:
Survivin与卵巢癌的分期和分级有关,并干扰肿瘤的药物敏感性。此外,发现Survivin表达受Sonichedgehog(Shh)途径调节,Krüppel样因子(KLF)家族蛋白,和p53通路。本研究的主要目的是评估Survivin的免疫组织化学表达的预后价值。Klf5,Klf11,嘘,一组高级别卵巢浆液性癌中的p53,p21和Mdm2。其他目的是比较高级别和低级别卵巢浆液性癌以及铂耐药和其他病例。最后一个目的是评估所研究蛋白质的免疫组织化学表达之间的相关性。回顾性队列研究评估Survivin的免疫组织化学表达,Klf5,Klf11,嘘,在73名受高级别卵巢浆液性癌影响的妇女和9名受低级别卵巢浆液性癌影响的原发性肿瘤样品的组织微阵列中,p53,p21和Mdm2。Klf5和Shh细胞质染色与短总生存期相关(分别为HR6.38,95%CI2.25-18.01,P<0.05和2.25,95%CI1.19-4.23,P<0.05)。此外,细胞质Klf5染色,高Klf11和p53核染色与铂耐药有关(P<0.05)。细胞质Shh评分与Klf5,Klf11,Mdm2和Survivin的免疫组织化学表达显着相关。我们的数据强调了Klf5和Shh作为预后标志物的可能作用,同时证实KLF家族蛋白和p53在卵巢癌耐药中的作用。此外,Shh似乎在卵巢肿瘤的细胞内网络中起重要作用。