Canalicular immunostaining of aminopeptidase N (CD13) as a diagnostic marker for hepatocellular carcinoma.
ABSTRACT Aminopeptidase N (CD13) is expressed in normal and neoplastic liver tissue, where it exhibits a characteristic canalicular pattern (CD13(can)), similar to that seen for CD10 and when antibodies crossreact with biliary glycoprotein I (p-CEA).
To compare the putative diagnostic use of CD13(can) in differentiating between hepatocellular (HCC) and non-hepatocellular carcinomas metastatic to the liver (non-HCC).
A retrospective study comparing 53 HCC specimens with 32 non-HCC specimens. Immunostaining was performed with HepPar1 and antibodies directed against CD10, CD13, p-CEA, and alpha fetoprotein (AFP).
In the HCC group, a canalicular staining pattern was found for CD13, p-CEA, and CD10 in 51, 43, and 33 specimens, respectively. HepPar1 was positive in 29 and AFP in 17 HCC specimens. In the non-HCC group, canalicular immunostaining for CD10 and p-CEA was confined to non-neoplastic liver tissue. One poorly differentiated cholangiocarcinoma showed apical expression of CD13, resembling to some extent CD13(can). Sensitivity and specificity were 96.2% and 97.0%, respectively, for CD13(can), 81.1% and 100% for p-CEA(can), 62.3% and 100%, for CD10(can), 54.7% and 99.9% for HepPar1, and 32.1% and 100% for AFP.
These results show that CD13(can) is more sensitive in differentiating between HCC and non-HCC than CD10(can), p-CEA(can), HepPar1, and AFP.
Full-textDOI: · Available from: Christoph Röcken, Jan 04, 2014
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ABSTRACT: Background:Novel biomarkers for prostate cancer (PC) are urgently needed. This study investigates the expression, epigenetic regulation, and prognostic potential of ANPEP in PC.Methods:Aminopeptidase N (APN; encoded by ANPEP) expression was analysed by immunohistochemistry using tissue microarrays representing 267 radical prostatectomy (RP) and 111 conservatively treated (CT) PC patients. Clinical end points were recurrence-free survival (RFS) and cancer-specific survival (CSS), respectively. The ANPEP promoter methylation levels were determined by bisulphite sequencing or MethyLight analysis in 278 nonmalignant and PC tissue samples, and in cell lines.Results:The APN expression was significantly downregulated in PC compared with nonmalignant prostate tissue samples. Aberrant promoter hypermethylation was frequently observed in PC tissue samples, and 5-aza-2'-deoxycytidine induced ANPEP expression in three hypermethylated prostate cell lines, suggesting epigenetic silencing. Negative APN immunoreactivity was significantly associated with short RFS and short CSS in the RP and CT cohort, respectively, independently of routine clinicopathological predictors. Combining APN with a known angiogenesis marker (vascular endothelial growth factor or microvessel density) improved risk prediction significantly in both cohorts.Conclusion:Our results suggest negative APN immunoreactivity as a new independent adverse prognostic factor for patients with clinically localised PC and, furthermore, that epigenetic mechanisms are involved in silencing of ANPEP in PC.British Journal of Cancer advance online publication, 15 January 2013; doi:10.1038/bjc.2012.549 www.bjcancer.com.British Journal of Cancer 01/2013; DOI:10.1038/bjc.2012.549 · 4.82 Impact Factor
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ABSTRACT: Processes that promote cancer progression such as angiogenesis require a functional interplay between malignant and nonmalignant cells in the tumor microenvironment. The metalloprotease aminopeptidase N (APN; CD13) is often overexpressed in tumor cells and has been implicated in angiogenesis and cancer progression. Our previous studies of APN-null mice revealed impaired neoangiogenesis in model systems without cancer cells and suggested the hypothesis that APN expressed by nonmalignant cells might promote tumor growth. We tested this hypothesis by comparing the effects of APN deficiency in allografted malignant (tumor) and nonmalignant (host) cells on tumor growth and metastasis in APN-null mice. In two independent tumor graft models, APN activity in both the tumors and the host cells cooperate to promote tumor vascularization and growth. Loss of APN expression by the host and/or the malignant cells also impaired lung metastasis in experimental mouse models. Thus, cooperation in APN expression by both cancer cells and nonmalignant stromal cells within the tumor microenvironment promotes angiogenesis, tumor growth, and metastasis.Proceedings of the National Academy of Sciences 01/2012; · 9.81 Impact Factor
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ABSTRACT: The polarized molecules predominately distributing at hepatocyte canalicular surface play a vital role in disclosing the process of bile formation and etiopathogenisis of cholestatic live diseases. Therefore, it is important to find novel polarized molecules on hepatocyte canalicular membrane. In the present study, canalicular membrane vesicles (CMVs) isolated from rat hepatocyte by density gradient centrifugation were used as immunogens to produce hybridoma and 46 strains of monoclonal antibodies (mAb) against CMVs were obtained. With a series of morphological assay methods, including immunohistochemistry, immunofluorescence and immuno-electron microscope, the antigens recognized by canalicular mAb1 (CM1) and canalicular mAb2 (CM2) were confirmed to predominately distribute at hepatocyte canalicular membrane. Transport activity assay revealed that CM2 could inhibit ATP-dependent E217βG uptake of rat hepatocyte CMVs. Meanwhile, Western blotting analysis showed that the molecular mass of CM2 antigen was approximately 110kDa, which was much less than Mr 180kDa of multidrug resistance-associated protein 2 (MRP2) involved in glucuronide transport. These data indicated that CM2 antigen might be a potential novel molecule participating in glucuronide transport on the hepatocyte canalicular membrane.European journal of histochemistry: EJH 07/2012; 56(3):e26. DOI:10.4081/ejh.2012.e26 · 2.24 Impact Factor