High GOLPH3 expression is associated with a more aggressive behavior of epithelial ovarian carcinoma

Abstract

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.