It was suggested that the enhancer of zeste homolog 2 (EZH2) gene is a putative candidate oncogene in several types of human cancer. The potential oncogenic role of EZH2 and its clinical/prognostic significance, however, in ovarian carcinoma are unclear. In this study, EZH2 expression was examined by immunohistochemistry (IHC) in cohorts of normal and tumorous ovarian tissues. High expression of EZH2 was examined in none of the normal ovaries, in 3% of the cystadenomas, in 23% of the borderline tumors and in 50% of the ovarian carcinomas, respectively. In the ovarian carcinomas, high expression of EZH2 was positively correlated with an ascending histological grade and/or advanced stage of the disease (P < 0.05). Moreover, high expression of EZH2 in ovarian carcinoma was determined to be a strong and an independent predictor of short overall survival (P < 0.05). In ovarian carcinoma HO-8910 and UACC-326 cell lines, EZH2 knockdown by RNA interference led to a G(1) phase cell cycle arrest, reduced cell growth/proliferation and inhibited cell migration and/or invasion in vitro. In addition, EZH2 knockdown was found to reduce transforming growth factor-beta1 (TGF-beta1) expression and increase E-cadherin expression either in the transcript or in the protein levels. Furthermore, a significant positive correlation between overexpression of EZH2 and TGF-beta1 in ovarian carcinoma tissues was observed (P < 0.001). These findings suggest a potential important role of EZH2 in the control of cell migration and/or invasion via the regulation of TGF-beta1 expression, and the high expression of EZH2, as detected by IHC, is an independent molecular marker for shortened survival time of patients with ovarian carcinoma.

Human interacting protein X1 (PinX1) has been identified as a critical telomerase inhibitor and proposed to be a putative tumor suppressor gene. Loss of PinX1 has been found in a large variety of malignancies, but the expression status in epithelial ovarian tumors has not been investigated. In this study, immunohistochemistry for PinX1 protein was performed on a tissue microarray (TMA) of epithelial ovarian tumors (informatively containing 25 cystadenomas, 29 borderline tumors, and 157 invasive carcinomas) and 12 normal ovaries. Receiver-operator curve (ROC) analysis was used to determine cut-off scores for tumor positivity and to evaluate patients' survival status. The threshold for PinX1 positivity was determined to be above 60% (area under the curve = 0.856, P < 0.001) based on the area under the ROC. Positive expression of PinX1 was observed in 100% of normal ovarian tissues, in 84% of cystadenomas, in 75.9% borderline tumors, and 66.2% of ovarian carcinomas. Decreased expression of PinX1 was strongly related to patients with poor prognostic factors regarding presence of lymph node metastasis (P = 0.024), distant metastasis (P < 0.001), and late International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001). In univariate survival analysis, a highly significant correlation between loss of PinX1 and shortened patient survival (mean, 48.2 months vs 99.2 months, P < 0.001) was displayed. Multivariate analysis demonstrated PinX1 expression (P = 0.027) was evaluated as an independent parameter. Our findings suggest that loss of PinX1 is an adverse independent molecular marker for epithelial ovarian carcinoma patients. PinX1 may be a novel target for telomerase-based anticancer therapy due to inhibiting telomerase activity. (Cancer Sci 2010; 101: 1543-1549 O varian cancer is the leading cause of death from a gynecological malignancy worldwide, with increasing incidence recently in Asian countries such as China and Singapore.(1) Due to the lack of reliable methods of early detection and the absence of specific symptoms, the majority of ovarian cancer patients (70%) were diagnosed at late stage, and the prognosis is very poor with a 5-year survival rate of <20%.(2)

The purpose of this study was to evaluate the association of expression level of α5β1-integrin and MMP-14 with clinicopathologic features and prognosis in colorectal cancer (CRC). The expressions of α5β1-integrin and MMP-14 in normal colorectal mucosa and CRC tissue were detected with immunohistochemistry. We estimated the five-year survival rate by the Kaplan-Meier method. The positive expressions rates of α5β1-integrin and MMP-14 in CRC tissue were 60.6% and 63.3% respectively, and there were significant differences on their positive expression rates between in CRC tissue and in normal colorectal mucosa(P<0.05). The expression rates of α5β1-integrin and MMP-14 in patients with poor histological differentiation, lymph node metastasis and high clinical staging were heightened. There was a significant difference (P<0.05) on the five-year survival rate for α5β1-integrin expression, which was 44.6% in positive groups and 75.5% in negative groups. And there was a significant difference (P<0.05) on the five-year survival rate for MMP-14 expression, which was 48.2% in positive group and 73.1% in negative group. The expression of α5β1-integrin and MMP-14 is correlated with the progression and metastasis of CRC, and α5β1-integrin and MMP-14 may be used as prognostic markers in CRC.Key words: CRC, immunohistochemistry, prognosis, survival CRC is the third most common cancer worldwide [1]. CRC is a cause of significant morbidity and cancer-related mortality in China both men and women. More than 17 million new cases of CRC were reported every year in China mainland. Despite recent treatment options and prognosis for patients with advanced CRC have improved through the development of novel drugs, progress in the treatment of CRC has been limited [2,3]. Most newly diagnosed patients will present with incurable disease, and have a median survival of less than 1 year. If metastasis has occurred, patient five-year survival rate after surgery falls dramatically from 90% to less than 10% [4]. It is, therefore, important to increase our understanding of the molecular changes leading to development, spread and metastasis of CRC and to identify potentially prognostic and predictive biomarkers for the disease.The conspicuous characteristic of malignant tumor is invasion and metastasis. To date, it is now clear that adhesive interaction play a critical role in the process of metastatic tumor dissemination [5].Cell adhesion molecules (CAMs) are involved in cell-cell and cell-extracellular matrix(ECM) binding, a highly complex process [6]. Integrins are the major adhesive molecules in cells and have been associated with metastasis of cancer cells. The integrins , a superfamily of heterodimer cell surface glycoprotein receptors composed of distinct α and β subunits [7], were originally described as cell adhesion receptors, but their functions in cell behavior including motility and invasion and their interactions with classical growth factor receptor signaling pathways have been increasingly recognized in the past few years [8]. Inte...