Open AccessDecreased expression of PinX1 protein is correlated with tumor development and is a new independent poor prognostic factor in ovarian carcinoma
Author(s) -
Cai MuYan,
Zhang Bin,
He WeiPeng,
Yang GuoFen,
Rao HuiLan,
Rao ZhiYue,
Wu QiuLiang,
Guan XinYuan,
Kung HsiangFu,
Zeng YiXin,
Xie Dan
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01560.x
Subject(s) - immunohistochemistry , univariate analysis , medicine , ovarian carcinoma , tissue microarray , pathology , metastasis , biology , oncology , ovarian cancer , cancer , multivariate analysis
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)