Cell adhesion molecules P-cadherin and CD24 are markers for carcinoma and dysplasia in the biliary tract
Department of Pathology, University Hospital Zurich, 8091 Zurich, Switzerland.Human pathology (Impact Factor: 2.77). 11/2010; 41(11):1558-65. DOI: 10.1016/j.humpath.2009.12.016
P-cadherin (CDH3) and CD24 are cell adhesion molecules that control morphogenic processes, cell motility, and invasive growth of tumor cells. The aim of our study was to investigate P-cadherin and CD24 expression in carcinomas and dysplastic lesions of the biliary tract and to evaluate the potential diagnostic usefulness of these cell adhesion molecules. Using immunohistochemistry on tissue microarrays, we analyzed P-cadherin, CD24, and p53 expression in 117 carcinomas of the biliary tract (19 intrahepatic cholangiocarcinomas, 59 extrahepatic cholangiocarcinomas, and 39 gallbladder carcinomas) and correlated our findings with clinicopathologic parameters. We found P-cadherin positivity in 37% of intrahepatic cholangiocarcinomas, 73% of extrahepatic cholangiocarcinomas, and 64% of gallbladder carcinomas, respectively. CD24 reactivity was observed in 21% of intrahepatic cholangiocarcinomas, 58% of extrahepatic cholangiocarcinomas, and 42% of gallbladder carcinomas. Nuclear p53 expression was found in 37% of intrahepatic cholangiocarcinomas, 46% of extrahepatic cholangiocarcinomas, and 45% of gallbladder carcinomas. We also studied P-cadherin, CD24, and p53 expression in normal (n = 30), inflamed (n = 22), and dysplastic (n = 21) biliary epithelium of extrahepatic bile ducts. Dysplastic biliary epithelium was positive for P-cadherin in 91%, for CD24 in 71%, and for p53 in 24% of lesions, respectively. In contrast, normal and inflamed epithelia were negative for all 3 proteins. We conclude that P-cadherin and CD24 are expressed in carcinomas of the biliary tract with high frequency and at an early stage of carcinogenesis. Therefore, they may be useful markers for early detection and as targets for therapy of cholangiocarcinoma.
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ABSTRACT: Hepatozelluläre Karzinome (HCC) und Gallengangskarzinome (CCC) haben eine schlechte Prognose, da sie häufig erst in fortgeschrittenen Stadien entdeckt werden und es bislang keine wirksame adjuvante Therapie gibt. Zur frühzeitigen Erkennung dieser Tumoren können Serummarker (z. B AFP, CA19-9) eingesetzt werden, die jedoch nur eine mäßige Sensitivität oder Spezifität aufweisen. Das Golgi-Apparat-assoziierte Protein GOLPH2 wurde im Gewebe und Serum von HCC- und CCC-Patienten nachgewiesen und kann für die Früherkennung dieser Tumoren eingesetzt werden. Der Goldstandard der Diagnose von HCC und CCC ist immer noch die Biopsie. Eine sichere Diagnosestellung ist jedoch bei zirrhotisch oder entzündlich verändertem Gewebe nicht immer rein morphologisch möglich. Neue immunhistochemische Marker können bei dieser wichtigen Differenzialdiagnose sehr hilfreich sein. Studien zeigten, dass das onkofetale IGF-II-mRNA-bindende Protein 3 (IMP3), die Zelladhäsionsmoleküle P-Cadherin und CD24, das Cancer-Testis-Antigen MAGE-C2/CT-10 sowie das Protein Periostin als Gewebsmarker in der Diagnostik für die Früherkennung von HCC und CCC sehr gut einsetzbar sind.Der Pathologe 11/2011; 32(2). DOI:10.1007/s00292-011-1467-6 · 0.39 Impact Factor
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ABSTRACT: Biliary tract cancer (BTC) is a fatal cancer originating from epithelial cells of the intra- and extra-hepatic biliary duct system and the gallbladder. Genes and pathways regulating stem and progenitor cells as well as cell-fate decisions are increasingly recognized in tumorigenesis. We evaluated the expression of Notch1, Notch2, and HES1 (hairy and enhancer of split 1), as well as the biliary cell-fate regulators SOX9 (SRY (sex determining region Y)-box 9) and HNF1β (hepatocyte nuclear factor 1β), in BTC for correlation with clinicopathological parameters. Tissue microarrays including normal bile ducts and 111 BTCs consisting of 17 intrahepatic cholangiocarcinomas, 58 extrahepatic cholangiocarcinomas, and 36 gallbladder carcinomas were analyzed using immunohistochemistry. Lack of cytoplasmic SOX9 expression was associated with a higher tumor grade (P=0.010) and a significantly reduced overall survival (P=0.002; median 6 months vs. 24 months) in univariate survival analysis, whereas lack of nuclear SOX9 expression was associated with a higher tumor stage (P=0.003). Notch pathway members showed high expression in BTC. However, no correlation was found between cytoplasmic or nuclear Notch1, Notch2, and HES1, as well as HNF1β expression, and any of the clinicopathological parameters. In multivariate analysis, cytoplasmic SOX9 expression was an independent prognostic factor for overall survival (P=0.031, relative risk=0.571). We show strong Notch pathway activation and identify SOX9 as a prognostic marker in BTC. These results substantiate diagnostic and therapeutic approaches targeting developmentally active genes and pathways.The American Journal of Gastroenterology 09/2011; 107(1):126-35. DOI:10.1038/ajg.2011.305 · 10.76 Impact Factor
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ABSTRACT: Recent studies have demonstrated that N-Myc downstream-regulated gene 2 (NDRG2) may reduce the metastatic potential of breast cancer and hepatocellular carcinoma cells by regulating the expression of CD24, which is expressed in a large variety of solid tumors. The aim of this study was to clarify the clinical value of NDRG2 and CD24 expression in primary gallbladder carcinoma (GBC). One hundred and thirty GBC tissues were evaluated by immunohistochemistry for NDRG2 and CD24 expression. The associations of NDRG2 and CD24 expression with the clinicopathological characteristics and the overall survival of patients with GBC were analyzed. NDRG2 and CD24 were positively expressed in 49/130 (37.69%) and 107/130 (82.31%) of GBC tissues, respectively. In addition, the tumors with the down-regulation of NDRG2 and the up-regulation of CD24 more frequently had lymph node metastasis and lymphovascular invasion. Moreover, the tumors with the down-regulation of NDRG2 and the up-regulation of CD24 tended to show deeper invasion depth and higher TNM stage. There was a negative correlation between NDRG2 expression and CD24 expression in GBC tissues (r = -0.86, P < 0.001). The patients with NDRG2 negative expression correlated with poor prognosis of GBC (P = 0.01), as opposed to CD24 (P = 0.01). The survival rate of the patients with NDRG2-/CD24+ expression was the lowest (P < 0.001), and conjoined expression of NDRG2-/CD24+ was an independent prognostic indicator of GBC (P = 0.003). Our data suggest that NDRG2 down-regulation or CD24 up-regulation is an important feature of GBC. A combined detection of NDRG2/CD24 co-expression may benefit us in prediction of the prognosis in GBC.Medical Oncology 12/2011; 29(3):1879-85. DOI:10.1007/s12032-011-0110-y · 2.63 Impact Factor
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