Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway.
Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0310 Oslo, Norway; University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, N-0316 Oslo, Norway.
Gynecol Oncol. 2014 Oct;135(1):118-24. doi: 10.1016/j.ygyno.2014.07.102. Epub 2014 Aug 2.
Wee1-like kinase (Wee1) is a tyrosine kinase which negatively regulates entry into mitosis at the G2 to M-phase transition and has a role in inhibition of unscheduled DNA replication in S-phase. The present study investigated the clinical role of Wee1 in advanced-stage (FIGO III-IV) ovarian serous carcinoma.
Wee1 protein expression was analyzed in 287 effusions using immunohistochemistry. Expression was analyzed for association with clinicopathologic parameters, including survival. Forty-five effusions were additionally studied using Western blotting. Wee1 was further silenced in SKOV3 and OVCAR8 cells by siRNA knockdown and proliferation was assessed.
Nuclear expression of Wee1 in tumor cells was observed in 265/287 (92%) and 45/45 (100%) effusions by immunohistochemistry and Western blotting, respectively. Wee1 expression by immunohistochemistry was significantly higher in post-chemotherapy disease recurrence compared to pre-chemotherapy effusions obtained at diagnosis (p=0.002). Wee1 silencing in SKOV3 and OVCAR8 cells reduced proliferation. In univariate survival analysis of the entire cohort, a trend was observed between high (>25% of cells) Wee1 expression and poor overall survival (p=0.083). Survival analysis for 109 patients with post-chemotherapy effusions showed significant association between Wee1 expression and poor overall survival (p=0.004), a finding which retained its independent prognostic role in Cox multivariate analysis (p=0.003).
Wee1 is frequently expressed in ovarian serous carcinoma effusions, and its expression is significantly higher following exposure to chemotherapy. The present study is the first to report that Wee1 is an independent prognostic marker in serous ovarian carcinoma.
Wee1 样激酶（Wee1）是一种酪氨酸激酶，可在 G2 期到 M 期过渡时负调控进入有丝分裂，并在 S 期抑制非计划的 DNA 复制中发挥作用。本研究探讨了 Wee1 在晚期（FIGO III-IV 期）卵巢浆液性癌中的临床作用。
使用免疫组织化学法分析 287 份积液中的 Wee1 蛋白表达。分析表达与临床病理参数的关系，包括生存情况。另外用 Western blot 法对 45 份积液进行了研究。通过 siRNA 敲低沉默 SKOV3 和 OVCAR8 细胞中的 Wee1，并评估增殖情况。
免疫组织化学和 Western blot 法分别在 287 份和 45 份积液中观察到肿瘤细胞的核表达 Wee1，阳性率分别为 92%和 100%。与诊断时获得的化疗前积液相比，化疗后疾病复发的积液中免疫组化检测到的 Wee1 表达明显更高（p=0.002）。沉默 SKOV3 和 OVCAR8 细胞中的 Wee1 可降低增殖。在整个队列的单因素生存分析中，高表达（>25%的细胞）Wee1 与总生存不良之间存在趋势（p=0.083）。对 109 例化疗后积液的生存分析显示，Wee1 表达与总生存不良之间存在显著关联（p=0.004），这一发现在 Cox 多因素分析中保留了其独立的预后作用（p=0.003）。
Wee1 在卵巢浆液性癌积液中频繁表达，且在接触化疗后表达显著升高。本研究首次报道 Wee1 是浆液性卵巢癌的独立预后标志物。
