Expression of mesothelin, fascin, and prostate stem cell antigen in primary ovarian mucinous tumors and their utility in differentiating primary ovarian mucinous tumors from metastatic pancreatic mucinous carcinomas in the ovary

Department of Pathology, The Johns Hopkins University School of Medicine and Hospital, Baltimore, MD 21231, USA.
International Journal of Gynecological Pathology (Impact Factor: 1.67). 02/2005; 24(1):67-72. DOI: 10.1097/01.pgp.0000139648.17750.35
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Metastatic pancreatic mucinous adenocarcinomas in the ovaries can be difficult to distinguish from primary ovarian mucinous neoplasms because the former can simulate the latter grossly and histologically and both tumor types share the same cytokeratin 7/cytokeratin 20 immunoprofile. We previously reported the utility of loss of Dpc4 expression in distinguishing metastatic pancreatic carcinomas from primary ovarian mucinous tumors. Recently several new pancreatic carcinoma markers have been identified, including mesothelin, fascin, and prostate stem cell antigen (PSCA). In this study we investigate the expression patterns of these markers in 35 primary ovarian mucinous tumors (28 atypical proliferative [borderline] tumors and 7 invasive carcinomas) and 11 metastatic pancreatic mucinous carcinomas in the ovary. Primary ovarian mucinous tumors expressed mesothelin (17%), fascin (26%), and PSCA (43%) less frequently than metastatic pancreatic adenocarcinomas (73%, 73%, and 82%, respectively). Expression of all three markers was seen only in metastatic pancreatic adenocarcinomas (45%), and coexpression of at least two markers was observed significantly more frequently in metastatic (82%) than primary ovarian mucinous tumors (17%). Our results indicate that an immunohistochemical panel including Dpc4, mesothelin, fascin, and PSCA is useful for evaluating difficult mucinous tumors in the ovary when the differential diagnosis includes metastatic pancreatic adenocarcinoma.

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    • "Alterations of prostate stem cell antigen (PSCA), mucin 1 (MUC1) and phospholipase C epsilon 1 (PLCE1) gene expression have been noted in gastrointestinal, bladder, prostate, breast cancers and are implicated in the processes of carcinogenesis (Zotter et al., 1988; Reiter et al., 1998; Sakamoto et al., 2008; Fu et al., 2012). PSCA gene was originally identified as a prostate cell surface specific marker and later was found to be overexpressed in several other human solid cancers (Reiter et al., 1998; Amara et al., 2001; Cao et al., 2005; Kawaguchi et al., 2010). It was also revealed that PSCA may be involved in cell proliferation, adhesion, migration and survival -the processes which are altered in carcinogenesis (Saffran et al., 2001; Eshel et al., 2002). "
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    ABSTRACT: Polymorphisms of genes encoding PSCA, PLCE1 and MUC1 have been associated with the risk of different cancers in genome wide association studies (GWAS). Up to date there are limited data on the role of these genetic alterations in colorectal cancer (CRC) development. The aim of this study was to evaluate potential associations between single nucleotide polymorphisms (SNPs) of genes encoding PSCA, PLCE1 and MUC1 and the presence of CRC in European populations. Gene polymorphisms were analyzed in 574 European subjects (controls: n=382; CRC: n=192). PSCA C>T (rs2294008), PSCA G>A (rs2976392), MUC1 A>G (rs4072037) and PLCE1 A>G (rs2274223) SNPs were genotyped by RT-PCR. The distribution of genotypes for all four SNPs was in line with the Hardy-Weinberg equilibrium (rs2294008, P=0.153; rs2976392, P=0.269; rs4072037, P=0.609; rs2274223, P=0.858). The distribution of genotypes and alleles of PSCA C>T, PSCA G>A, MUC1 A>G and PLCE1 A>G SNPs was similar among controls and CRC patient groups (P>0.05). GG genotype of MUC1 SNP was more frequent in CRC patients (24.0%) than in controls (20.2%); however, this association failed to reach significance (OR-1.45, P=0.15). Overall, in the present study SNPs of PSCA (rs2294008, rs2976392), MUC1 (rs4072037) and PLCE1 (rs2274223) genes were not associated with the presence of CRC. Gene polymorphisms of PSCA, PLCE1 and MUC1 genes are not associated with the presence of CRC in European subjects.
    Asian Pacific journal of cancer prevention: APJCP 08/2015; 16(14):6027-32. DOI:10.7314/APJCP.2015.16.14.6027 · 2.51 Impact Factor
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    • "No significant difference in staining for fascin was observed between borderline and malignant tumors in which 68% and 40% of malignant and borderline tumors, respectively, had positive staining . Overall, the findings obtained in the present study reflect those of other studies that investigated fascin expression in ovarian tumors [7] [17] [19] [20]. There are a few studies in the literature reporting EMMPRIN expression in ovarian tumors. "
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    ABSTRACT: Objectives The aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis. Materials and methods An immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score. Results Both of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression. Conclusions In ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors.
    Pathology - Research and Practice 12/2014; 210(12). DOI:10.1016/j.prp.2014.07.003 · 1.40 Impact Factor
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    • "PSCA is considered to be involved in the cell adhesion (Raff et al., 2009), signal transduction (Matsuo et al., 2009; Qiao and Feng, 2012), cell-proliferation inhibition and/or cell-death induction activity though, its biological functions in carcinogenesis are still obscure (Saeki et al., 2010). PSCA is upregulated (protein or mRNA) in cancer of the prostate (Zhigang and Wenlv, 2004), bladder (Fu et al., 2012), endometrium (Liu et al., 2010) pancreas (Argani et al., 2001), ovary (Cao et al., 2005), central nervous system (Geiger et al., 2011), lung (Kawaguchi et al., 2010) and kidney (Elsamman et al., 2006), etc. and found to be associated with increasing disease stage and other adverse prognostic features (Smith et al., 2012). PSCA down-regulation and growth suppressive effects have also been reported in upper gastrointestinal carcinogenesis such as gastric, esophageal, and gallbladder cancer (Bahrenberg et al., 2000; Sakamoto et al., 2008), showing tissue-specific pattern of PSCA expression in cancer cells depending on the epithelium of their origin. "
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    ABSTRACT: Background and aim PSCA is a tissue specific tumor suppressor or oncogene which has been found to be associated with several human tumors including gallbladder cancer. It is considered to be involved in the cell-proliferation inhibition and /or cell-death induction activity. Therefore, we aimed to investigate the role of PSCA gene polymorphisms in gallbladder cancer risk in North Indian population. Methodology A total of 405 gallbladder cancer patients and 247 healthy controls were included in the case-control study for risk prediction. We examined the association of two functional SNPs, rs2294008 and rs2978974 in PSCA gene by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. Linkage disequilibrium and haplotype analysis was done with the help of SNPstats software. FDR test was used to correct for multiple comparisons. No significant associations of rs2294008 and rs2978974 genetic variants of the PSCA gene were found with GBC risk at allele, genotype or haplotype levels. Stratifying the subjects on the basis of gallstone also did not show any significant result. However, on gender stratification, we found a significant association of Trs2294008-Grs2978974 haplotype with higher risk of GBC in females (FDR Pcorr=0.021, OR=1.6). In contrary, Trs2294008-A rs2978974 haplotype conferred significant lower risk in males (FDR Pcorr=0.013; OR=0.25). These findings suggest that PSCA genetic variants may have a significant effect on GBC susceptibility in a gender specific manner.
    Gene 08/2013; 530(2). DOI:10.1016/j.gene.2013.08.058 · 2.14 Impact Factor
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