Differential Expression of Hypoxia-Inducible Protein 2 Among Different Histological Types of Epithelial Ovarian Cancer and in Clear Cell Adenocarcinomas
Differential Expression of Hypoxia-Inducible Protein 2 Among Different Histological Types of Epithelial Ovarian Cancer and in Clear Cell Adenocarcinomas
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DOI：
10.1111/igc.0b013e3181ca1e16
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发表时间：
2010-02-01
影响因子：
4.8
通讯作者：
Aoki, Daisuke
中科院分区：
文献类型：
--
作者：
Nishimura, Sadako;Tsuda, Hiroshi;Aoki, Daisuke
目的：上皮性卵巢癌（Epithelial ovarian cancer，EOC）可分为5种主要的组织学类型.其中，透明细胞腺癌（CCC）与其他组织学类型相比，对化疗反应差，预后差。以前，我们报道了低氧诱导蛋白2（HIGH 2）基因可能是一个新的生物标志物的CCC，基于其表达谱。在这项研究中，我们产生了一个多克隆抗血清，以探讨使用的HIG 2作为一个预测性生物标志物在EOC。方法：采用免疫组化法检测254例卵巢上皮性癌、17例子宫内膜癌和29例肾性癌组织中缺氧诱导蛋白2的表达，并与175例正常卵巢组织进行比较。细胞质中的HIGH 2表达在卵巢CCC中（83.1%）显著高于浆液性（54.9%，P = 0.0001）、粘液性（40%，P = 0.00002）或类囊腺癌（58.1%，P = 0.003）。24例胞浆有HIG 2表达的CCC患者化疗有效率高于6例胞浆无HIG 2表达的CCC患者（62.5% [15/24] vs 0% [0/6]，P = 0.02）。与此相反，有没有核HIG 2表达和化疗反应之间的关系。结论：缺氧诱导蛋白2可作为卵巢CCC的早期诊断和化疗疗效的预测指标，但不能预测CCC患者的生存率。
Objectives: Epithelial ovarian cancer (EOC) can be classified into 5 major histological types. Among them, clear cell adenocarcinoma (CCC) has a poor response to chemotherapy and poor prognosis compared with other histological types. Previously, we reported that the hypoxia-inducible protein 2 (HIG2) gene might be a new biomarker for CCCs, based on its expression profile. In this study, we generated a polyclonal antiserum to HIG2 to explore the use of HIG2 as a predictive biomarker in EOC. In addition, HIG2 expression was evaluated in uterine endometrial and renal CCCs.Methods: Hypoxia-inducible protein 2 expression was analyzed by immunohistochemistry in formalin-fixed surgical samples from 254 EOC, 17 endometrial, and 29 renal CCC patients.Results: Hypoxia-inducible protein 2 is expressed in 175 of 254 ovarian cancer cases. Cytoplasmic HIG2 expression is significantly more frequent in ovarian CCC (83.1%) than in serous (54.9%, P = 0.0001), mucinous (40%, P = 0.00002), or endometrioid (58.1%, P = 0.003) adenocarcinoma. The chemoresponse rate was higher in 24 ovarian CCC patients with cytoplasmic HIG2 expression than in 6 CCC patients without HIG2 expression (62.5% [15/24] vs 0% [0/6], P = 0.02). In contrast, there was no relationship between nuclear HIG2 expression and chemoresponse. Cytoplasmic and nuclear HIG2 expressions are significantly more frequent in ovarian and uterine than renal CCC (P = 0.04).Conclusions: Hypoxia-inducible protein 2 may be used as a marker for early detection of ovarian CCCs or for prediction of response to chemotherapy, but HIG2 expression does not predict survival of patients with CCC.