Loss of SerpinA5 protein expression is associated with advanced-stage serous ovarian tumors

Abstract

Epithelial ovarian cancer, the most lethal neoplasm of the female genital tract, is usually diagnosed at an advanced stage as obvious symptoms are absent at early stages. This disease is believed to originate from malignant transformation of the ovarian surface epithelium or fallopian tube. Histologically, several subtypes are being recognized, with serous histology accounting for the majority of cases. Serous tumors include serous borderline tumors and serous carcinomas. A better understanding of the tumor biology and molecular mechanisms involved in these tumors is needed, as both patient management and prognosis differ substantially. Previous microarray analysis identified SerpinA5, a uPA inhibitor, as key regulator for indolent borderline behavior. As carcinomas are characterized by loss of SerpinA5 mRNA expression, we hypothesized that SerpinA5 protein expression is reduced or lost in carcinomas when compared with borderline tumors. We performed SerpinA5 immunohistochemical staining on 32 serous borderline tumors, 187 primary serous carcinomas and 62 serous omental metastases. Reduced or absent SerpinA5 protein staining was observed in carcinomas when compared with borderline tumors (Po0.001). SerpinA5 protein expression was significantly lowered in the omental metastases (Po0.001) when compared with the matching primary carcinoma. Interestingly, SerpinA5 protein expression was reduced in advanced-stage borderline tumors, often characterized by micropapillary growth and/or microinvasion, when compared with early-stage borderline tumors (P ¼ 0.015). In conclusion, SerpinA5 expression is significantly reduced in advanced-stage serous borderline tumors and serous carcinomas when compared with the early-stage counterparts, and reduction of expression is linked to more aggressive features of borderline tumors.

Ovarian cyst fluid is a rich proteome resource for detection of new tumor biomarkers

“…PCI is expressed in various human fluids and tissues but has not previously been described in ovarian cyst fluids. Gene and protein expression analysis revealed SERPINA5, the gene encoding PCI, as down-regulated in serous ovarian carcinomas compared with serous borderline tumors, which is consistent with our MS results [30,31]. SERPINA5 expression is decreased in renal and prostate cancer and elevated levels have been related to better survival in breast cancer [29,32,33].…”

Identification of CpG Sites of SERPINA5 Promoter with Opposite Methylation Patterns in Benign and Malignant Prostate Cells

“…Several studies indicated a protective role of SERPINA5 against tumor development, invasiveness, and metastasis (3,10,11,15,21). Elevated protein levels were detected in normal prostatic epithelia compared to tumor tissue, with a subpopulation of high-grade tumor cells having undetectable amounts of SERPINA5.…”

“…On the other hand, SERPINA5 limited cell migration by direct interaction with fibronectin and disruption of the fibronectin-integrin signalling pathway, as shown in hepatocellular carcinoma (10). Down-regulation of SERPINA5 was demonstrated in serous ovarian carcinomas, renal and breast cancers (8,(11)(12)(13)(14). In breast cancer, elevated levels of SERPINA5 correlated with increased survival and thus were considered as a positive prognostic factor in this disease (15).…”

Interaction of Protein C Inhibitor with the Type II Transmembrane Serine Protease Enteropeptidase

“…So far, very little is known about these functions. PCI might have a protective effect against cancer progression [25]–[29].…”