Department of Gynecology and Obstetrics, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, People's Republic of China,
Virchows Arch. 2014 Apr;464(4):443-52. doi: 10.1007/s00428-014-1536-3. Epub 2014 Jan 24.
Overexpression of GOLPH3 (Golgi phosphoprotein 3, 34 kDa) is associated with the progression of many solid tumor types leading to an unfavorable clinical outcome. The present study examined the association between GOLPH3 expression and tumor development, clinicopathological factors, and prognosis of epithelial ovarian carcinoma. GOLPH3 expression was examined by immunohistochemistry in 18 normal ovarian samples, 28 benign tumors, 55 serous borderline ovarian tumors, and 135 epithelial ovarian carcinomas. The association of GOLPH3 expression with clinical characteristics, response to chemotherapy, and overall survival of epithelial ovarian carcinoma patients was analyzed on fresh tissue samples. GOLPH3 mRNA and protein expression in ovarian cancer and normal ovarian tissues were detected by real-time quantitative RT-PCR and Western blotting, respectively. The results are the following: (1) GOLPH3 immunostaining localized to the cytoplasm in two patterns, condensed into large granules with perinuclear distribution, and dispersed in the cytoplasm as fine granules. (2) GOLPH3 expression was higher in epithelial ovarian carcinoma than in normal ovarian tissues at the mRNA and protein level. The frequency of high-level expression of GOLPH3 increased progressively from benign (cystadenoma) to borderline neoplasms to malignant lesions. (3) Dispersed cytoplasmic GOLPH3 expression in epithelial ovarian carcinoma patients was highly correlated with FIGO stage (p < 0.001), tumor histological grade (p = 0.003), lymph node involvement (p = 0.001), and chemotherapy response (p = 0.034). (4) A dispersed pattern of GOLPH3 expression was an independent prognostic factor for poor overall survival. Patients with low dispersed cytoplasmic GOLPH3 expression had significantly longer overall survival than patients with high dispersed cytoplasmic expression. In contrast, GOLPH3 condensed expression was not correlated with clinicopathological features, chemotherapy response, or prognosis. GOLPH3 gene expression might play a role in tumorigenesis in epithelial ovarian carcinoma as upregulation of GOLPH3 expression is associated with a more aggressive tumor phenotype. GOLPH3 immunohistochemistry may be of value to predict the outcome of ovarian carcinoma patients.
高尔基体磷蛋白 3(Golgi phosphoprotein 3,34 kDa)过表达与许多实体肿瘤类型的进展相关,导致临床结局不佳。本研究探讨了 GOLPH3 表达与上皮性卵巢癌的肿瘤发生、临床病理因素和预后的关系。采用免疫组织化学方法检测 18 例正常卵巢组织、28 例良性肿瘤、55 例交界性浆液性卵巢肿瘤和 135 例上皮性卵巢癌中 GOLPH3 的表达。在上皮性卵巢癌患者的新鲜组织标本上分析了 GOLPH3 表达与临床特征、化疗反应和总生存的关系。采用实时定量 RT-PCR 和 Western blot 检测卵巢癌和正常卵巢组织中 GOLPH3 mRNA 和蛋白的表达。结果如下:(1)GOLPH3 免疫染色定位于细胞质中,呈两种模式:浓缩成具有核周分布的大颗粒和分散成细胞质中的细颗粒。(2)上皮性卵巢癌中 GOLPH3 的 mRNA 和蛋白表达均高于正常卵巢组织。高水平 GOLPH3 表达的频率从良性(囊腺瘤)到交界性肿瘤再到恶性病变逐渐增加。(3)上皮性卵巢癌患者细胞质中分散的 GOLPH3 表达与 FIGO 分期(p<0.001)、肿瘤组织学分级(p=0.003)、淋巴结受累(p=0.001)和化疗反应(p=0.034)高度相关。(4)分散的 GOLPH3 表达模式是总生存不良的独立预后因素。低分散细胞质 GOLPH3 表达的患者总生存时间明显长于高分散细胞质表达的患者。相比之下,GOLPH3 浓缩表达与临床病理特征、化疗反应或预后无关。GOLPH3 基因表达可能在上皮性卵巢癌的肿瘤发生中起作用,因为 GOLPH3 表达的上调与更具侵袭性的肿瘤表型相关。GOLPH3 免疫组化可能有助于预测卵巢癌患者的预后。