Academic Unit of Obstetrics and Gynaecology; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Infant Health, University of Genoa, Genova 16132, Italy; Ennergi Research (non-profit organization), 33050 Lestizza UD, Italy.
Institute of Pathology, DAME, University Hospital of Udine, 33100 Udine UD, Italy.
Hum Pathol. 2022 Sep;127:92-101. doi: 10.1016/j.humpath.2022.06.023. Epub 2022 Jun 28.
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.
Survivin 先前与卵巢癌的肿瘤分期和分级有关，并干扰肿瘤的药物敏感性。此外，Survivin 的表达被发现受到 Sonic hedgehog (Shh) 途径、Krüppel-like factor (KLF) 家族蛋白和 p53 途径的调节。本研究的主要目的是评估 Survivin、Klf5、Klf11、Shh、p53、p21 和 Mdm2 的免疫组织化学表达在高级别卵巢浆液性癌队列中的预后价值。其他目的是比较高低级别卵巢浆液性癌之间以及铂耐药与其他病例之间的差异。最后一个目的是评估研究蛋白的免疫组织化学表达之间的相关性。回顾性队列研究，评估 73 例高级别卵巢浆液性癌和 9 例低级别卵巢浆液性癌患者的原发性肿瘤样本组织微阵列中 Survivin、Klf5、Klf11、Shh、p53、p21 和 Mdm2 的免疫组织化学表达。细胞质 Klf5 染色与总生存期缩短相关（HR 6.38，95%CI 2.25-18.01，P<.05 和 2.25，95%CI 1.19-4.23，P<.05）。此外，细胞质 Klf5 染色、高 Klf11 和核 p53 染色与铂耐药相关（P<.05）。细胞质 Shh 评分与 Klf5、Klf11、Mdm2 和 Survivin 的免疫组织化学表达显著相关。我们的数据强调了 Klf5 和 Shh 作为预后标志物的可能作用，同时证实了 KLF 家族蛋白和 p53 在卵巢癌耐药中的作用。此外，Shh 似乎在卵巢肿瘤发生的细胞内网络中发挥重要作用。
Zotero 插件