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Co-expression of CDX2 and MUC2 in gastric carcinomas: Correlations with clinico-pathological parameters and prognosis

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World Journal of Gastroenterology 2005年第21期11卷 3182-3188页

作者： Kristina Roessler Stefan p.M(o|¨)nig paul M.Schneider Franz-Georg Hanisch Stephanie Landsberg Juergen Thiele Arnulf H.H(o|¨)lscher hans p.dienes Stephan E.Baldus Institute of pathology University of Cologne 50931 Cologne Germany Department of Visceral and Vascular Surgery University of Cologne 50931 Cologne Germany Center of Biochemistry University of Cologne Cologne Germany Institute of pathology University of Cologne 50931 CologneGermany Department of Visceral and Vascular Surgery University of Cologne 50931 Cologne Germany

AIM: To evaluate the role of CDX2 homeobox protein as a predictor for cancer progression and prognosis as well as its correlation with MUC2 expression. CDX2 represents a transcription factor for various intestinal genes (including MUC2) and thus an important regulator of intestinal differentiation, which could previously be identified in gastric carcinomas and intestinal metaplasia. METHODS: Formalin-fixed and paraffin-embedded tissues from 190 gastric carcinoma patients were stained with monodonal antibodies recognizing CDX2 and MUC2, respectively. Immunoreactivity was evaluated semiquantitatively and statistical analyses including x2 tests, uni- and multi-variate survival analyses were performed. RESULTS: CDX2 was mostly expressed in a nuclear or supranuclear pattern,whereas MUC2 showed an almost exclusive supranuclear *** antigens were present in >80% of areas exhibiting intestinal metaplasia. An immunoreactivity in >5% of the tumor area was observed in 57% (CDX2) or in 21% (MUC2) of the *** presence of both molecules did not correlate with WHO, Lauren and Goseki classification (with the exception of a significantly stronger MUC2 expression in mucinous tumors). CDX2 correlated with a lower pT and pN stage in the subgroups of intestinal and stage I cancers and was associated with MUC2 positivity.A prognostic impact of CDX2 or MUC2 was not observed. CONCLUSION: CDX2 and MUC2 play an important role in the differentiation of normal, inflamed, and neoplastic gastric tissues. According to our results, loss of CDX2 may represent a marker of tumor progression in early gastric cancer and carcinomas with an intestinal phenotype.

关键词： CDX2 MUC2 Monoclonal antibody Gastric carcinoma prognosis

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Severe chronic diarrhea and weight loss in cholesteryl ester storage disease: A case report

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World Journal of Gastroenterology 2005年第15期11卷 2364-2366页

作者： Uta Drebber Matthias Andersen hans U Kasper peter Lohse Manfred Stolte hans p.dienes Institute of pathology Department of Internal Medicine Department of Clinical Chemistry-Grosshadern

AIM: An inherited deficiency of human lysosomal acid lipase (LAL)results in the rare conditions of Wolman disease and cholesteryl ester storage disease (CESD). We want to present the rare case of CESD in an ***: We report about an adult female patient with severe chronic diarrhea and weight loss as a consequence of CESD. Clinical examination revealed signs of malabsorption and slightly elevated liver ***: Histopathologic changes in the liver tissue and DNA sequence analysis confirmed the diagnosis of CESD due to homozygosity for the most common CESD mutation,a G934A splice site defect encoded by exon 8 of the lysosomal acid lipase (LIpA) ***: It is the first case in the literature with diarrhea as a putative symptom of CESD in adult patients.

关键词： CESD Acid esterase Hydrolase Liver biopsy pathology Diarrhea

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Liver tumor infiltrating lymphocytes: Comparison of hepatocellular and cholangiolar carcinoma

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World Journal of Gastroenterology 2009年第40期15卷 5053-5057页

作者： hans-Udo Kasper Uta Drebber Dirk Ludger Stippel hans peter dienes Anton Gillessen Department of pathology Medical CenterClemenshospital Münster Department of pathology University of Cologne Department of Visceral and Vascular Surgery University of Cologne Department of Gastroenterology Herz-Jesu-Hospital Hiltrup

AIM: To investigate the role of tumor inf iltrating lym-phocytes (TIL) in primary hepatocellular and cholangio-lar carcinomas of the ***: Immunohistochemical analysis was per-formed including antibodies to CD3, CD4, CD8, CD20, CD56 and TIA-1 in formalin-f ixed and paraff in-embed-ded tissue of 35 liver resection specimens of hepatocel-lular or cholangiocellular carcinomas. Semiquantitative evaluation was performed with emphasis on the area of the tumor itself and of the tumor/liver ***: All hepatocellular carcinomas showed in-filtration of lymphocytes predominantly around the tumor in the tumor/liver interface consisting mainly of CD3+ CD4+ T lymphocytes [164.3/10 high power f ields (HpF)] and in the tumor itself of CD8+ cells (54.9/10 HpF). Cholangiocarcinomas contained a heterogeneous amount of TIL, composed mainly of CD3+ T cells with a predominance of CD8+ cells in the tumor tissue (52.6/10 HpF) and of CD4+ cells in the interface region (223.1/10 HpF). CD56+ cells of the innate immune system were scarce. There was no significant difference between hepatocellular or cholangiolar carcinoma. No correlation with the clinicopathological data was seen. CONCLUSION: Liver TIL consists of intratumoral CD8+ T cells and peritumoral CD4+ T cells indepen-dent of histogenetic origin. Different functions of lym-phocytes in these regions seem possible.

关键词： Liver neoplasms Hepatocellular carcinoma Lymphocytes Immunologic factors Cholangiocarcinoma

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pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases

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World Journal of Gastroenterology 2010年第46期16卷 5830-5837页

作者： Johannes W Rey Andrea Noetel Aline Hardt Ali Canbay Hakan Alakus Axel zur Hausen hans peter dienes Uta Drebber Margarete Odenthal Institute for pathology University Hospital of Freiburg Department of Gastroenterology and Hepatology University Hospital of Essen Department of General Visceral and Cancer SurgeryUniversity Hospital of Cologne

AIM:To test the occurrence of the pro12Ala mutation of the peroxisome proliferator-activated receptor-γ (ppARγ)2-gene in patients with non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD).METHODS:DNA from a total of 622 specimens including 259 blood samples of healthy blood donors and 363 histologically categorized liver biopsies of patients with NAFLD (n=263) and AFLD (n=100) were analyzed by Real-time polymerase chain reaction using allele-specific ***:In the NAFLD and the AFLD collective,3% of the patients showed homozygous occurrence of the Ala12 ppARγ2-allele,differing from only 1.5% cases in the healthy *** NAFLD patients,a high incidence of the Ala12 mutant was not associated with the progression of fatty liver ***,we observed a significantly higher risk (odds ratio=2.50,CI:1.05-5.90,p=0.028) in AFLD patients carrying the mutated Ala12 allele to develop inflammatory *** linkage of the malfunctioning Ala12-positive ppARγ2 isoform to an increased risk in patients with AFLD to develop severe steatohepatitis and fibrosis indicates a more prominent anti-inflammatory impact of ppARγ2 in progression of AFLD than of ***:In AFLD patients,the pro12Ala single nuclear polymorphism should be studied more extensively in order to serve as a novel candidate in biomarker screening for improved prognosis.

关键词： Single nucleotide polymorphism peroxisome proliferator-activated receptor γ Non-alcoholic steatohepatitis Alcoholic steatohepatitis Inflammation Fibrosis Hepatitis Steatosis Steatohepatitis

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Nucleoporin 88 expression in hepatitis B and C virus-related liver diseases

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World Journal of Gastroenterology 2006年第36期12卷 5870-5874页

作者： Martina Knoess Anna Kordelia Kurz Olga Goreva Nuran Bektas Kai Breuhahn Magarethe Odenthal peter Schirmacher hans peter dienes C Thomas Bock hanswalter Zentgraf Axel zur Hausen Institute of pathology University Hospital Cologne Cologne Germany Department of Hematology/Oncology Freiburg University Medical Center Freiburg Germany Institute of pathology University of Heidelberg Heidelberg Germany Department of Molecular pathology University Hospital Tübingen Germany German Cancer Research Center DKFZ Applied Tumor Virology Heidelberg Germany Institute of pathology University Hospital Freiburg Freiburg Germany

AIM: To investigate the expression of nucleoporin 88 (Nup88) in hepatitis B virus (HBV) and C virus (HCV)-related liver diseases. METHODS: We generated a new monoclonal Nup88 antibody to investigate the Nup88 protein expression by immunohistochemistry (IHC) in 294 paraffin-embedded liver specimens comprising all stages of hepatocellular carcinogenesis. In addition, in cell culture experiments HBV-positive (HepG2.2.15 and HB611) and HBV-negative (HepG2) hepatoma cell lines were tested for the Nup88 expression by Western-immunoblotting to test data obtained by ***: Specific Nup88 expression was found in chronic HCV hepatitis and unspecific chronic hepatitis, whereas no or very weak Nup88 expression was detected in normal liver. The Nup88 expression was markedly reduced or missing in mild chronic HBV infection and inversely correlated with HBcAg expression. Irrespective of the HBV- or HCV-status, increasing Nup88 expression was observed in cirrhosis and dysplastic nodules, and Nup88 was highly expressed in hepatocellular carcinomas. The intensity of Nup88 expression significantly increased during carcinogenesis (p p p88 protein expression was significantly downregulated in HBV-positive HepG2.2.15 (p p pared to HBV-negative HepG2 cells. CONCLUSION: Based on our immunohistochemical data, HBV and HCV are unlikely to influence the expression of Nup88 in cirrhotic and neoplastic liver tissue, but point to an interaction of HBV with the nuclear pore in chronic hepatitis. The expression of Nup88 in nonneoplastic liver tissue might reflect enhanced metabolic activity of the liver tissue. Our data strongly indicate a dichotomous role for Nup88 in non-neoplastic and neoplastic conditions of the liver.

关键词： Nucleoporin 88 Hepatitis B and C virus Hepatocellular carcinogenesis

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Simultaneous occurrence of a hepatocellular carcinoma and a hepatic non-Hodgkin's lymphoma infi ltration

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World Journal of Hepatology 2010年第6期2卷 246-250页

作者： Sabine Heidecke Dirk L Stippel Arnulf H Hoelscher Inga Wedemeyer hans-peter dienes Uta Drebber Department of General- Visceral- and Cancer Surgery University Hospital of Cologne Department of pathology University Hospital of Cologne

To investigate the simultaneous occurrence of hepatocellular carcinoma and non-Hodgkin's lymphoma, we report the case of a 70 year old patient with a primary diagnosis of non-Hodgkin's lymphoma in 2002. In a routine follow up investigation of his chronic lymphocytic leukemia a newly detected mass in the Couinaud's segments 2 and 3 was found. No hepatitis C virus or hepatitis B virus infection or cirrhosis was evident. After laparoscopic segmentectomy the histological examination revealed a hepatocellular carcinoma. While the relation between liver parenchyma damages and hepatocellular carcinoma or non-Hodgkin's lymphoma is well known, only a few publications have focused on the coexistence of hepatocellular carcinoma and non-Hodgkin's lymphoma. With this case we demonstrate the coexistence of these diseases without having a pre- damaged liver parenchyma.

关键词： Hepatocellular carcinoma Non-Hodgkin’s lymphoma Etiology Carcinogenesis Histology

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