Expression and clinical role of DJ-1, a negative regulator of PTEN, in ovarian carcinoma

Summary The aim of this study was to analyze the expressionand clinical role of DJ-1, a negative regulator of PTEN(phosphatase and tensinhomolog deleted on chromosome 10), in ovarian carcinoma, and investigate the putative association between DJ-1 levels and expressionof its transcriptional regulatorsspecificity protein 1 (Sp1) and specificity protein 3 (Sp3). Effusions(n = 72) and solid tumors (n = 57, 42 primary and 15 metastases) were analyzed for DJ-1 messenger RNA (mRNA) expressionusing reverse transcriptase–polymerase chain reaction. Most specimens (48 effusions, 50 solid tumors) were additionally analyzed for Sp1 and Sp3 mRNA expression. PTENprotein expressionwas analyzed in 201 effusionsand 92 solid tumors using immunohistochemistry. DJ-1 mRNA was expressedin more than 80% of specimens, with no preferential anatomical site. DJ-1 expressionwas positively associated with Sp1 expressionin effusions( P = .03) and with Sp1 ( P = .02) and Sp3 ( P = .002) expressionin solid tumors. In effusions, DJ-1 expressionwas higher in postchemotherapy compared with prechemotherapy specimens ( P = .012). Higher DJ-1 levels ( P = .027) and more advanced FIGO stage (IV versus III; P = .003) correlated with shorter progression-free survival in univariate analysis for patients with postchemotherapy effusions. PTEN expressionwas low in effusionsand solid tumors (23% and 13%, respectively), and its expressionshowed no association with DJ-1 levels or survival. Our data show that DJ-1 is frequently expressedin advanced-stage ovarian carcinoma at all anatomical sites and is coexpressed with its transcriptional regulatorsSp1 and Sp3. In contrast, PTEN expressionis infrequent in this disease. These findings may provide one of the molecular mechanisms that mediate cancer cell survival and aggressiveness in this tumor.