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World Journal of Gastroenterology 2007年第35期13卷 4755-4760页

作者： Yves Deugnier bruno turlin Liver Unit and CIC INSERM 0203 Pontchaillou University HospitalRennes 35033France Department of Pathology and INSERM U 522 Pontchaillou University HospitalRennes 35033France

Although progress in imaging and genetics allow for a noninvasive diagnosis of most cases of genetic iron overload, liver pathology remains often useful （1） to assess prognosis by grading fibrosis and seeking for associated lesions and （2） to guide the etiological diagnosis, especially when no molecular marker is available. Then, the type of liver siderosis （parenchymal, mesenchymal or mixed） and its distribution throughout the Iobule and the liver are useful means for suggesting its etiology： HLA-linked hemochromatosis gene （HFE） hemochromatosis or other rare genetic hemochromatosis, nonhemochromatotic genetic iron overload （ferroportin disease, aceruloplasminemia）, or iron overload secondary to excessive iron supply, inflammatory syndrome, noncirrhotic chronic liver diseases including dysmetabolic iron overload syndrome, cirrhosis, and blood disorders.

关键词： Iron Liver Biopsy Hemochromatosis Ferroportin HLA-linked hemochromatosis gene Hepcidin Metabolic syndrome

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Prokineticin 2/Bv8 is expressed in Kupffer cells in liver and is down regulated in human hepatocellular carcinoma

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World Journal of Gastroenterology 2008年第8期14卷 1182-1191页

作者： Justin Monnier Claire Piquet-Pellorce Jean-Jacques Feige Orlando Musso bruno Clément bruno turlin Nathalie Théret Michel Samson INSERM U620 Université de Rennes 1 IFR140 2 avenue du Pr. Léon Bernard Rennes cedex 35043 France INSERM U522 Rennes France INSERM U878 Grenoble France Service d'Anatomo-pathologie CHU Pontchaillou Rennes France

AIM： TO study the implication of prokineticin 1 （PKI/EGVEGF） and prokineticin 2 （PK2/13v8） in hepatocellular carcinoma angiogenesis.METHODS： The gene induction of PK1/EG-VEGF and PK2/Bv8 was investigated in 10 normal, 28 fibrotic and 28 tumoral livers by using real time PCR. Their expression was compared to the expression of VEGF （an angiogenesis marker）, vWF （an endothelial cell marker） and to CD68 （a monocyte/macrophage marker）. Furthermore, the rnRNA levels of PK1/EG-VEGF, PK2/Bv8, prokineticin receptor 1 and 2 were evaluated by real time PCR in isolated liver cell populations. Finally, PK2/Bv8 protein was detected in normal liver paraffin sections and in isolated liver cells by immunohistochernistry and immunocytochemistry.RESULTS： PK2/Bv8 mRNA but not PK1/EG-VEGF was expressed in all types of normal liver samples examined. In the context of liver tumor development, we reported that PK2/13v8 correlates only with CD68 and showed a significant decrease in expression as the pathology evolves towards cancer. Whereas, VEGF and vWF mRNA were significantly upregulated in both fibrosis and HCC,as expected. In addition, out of all isolated liver cells examined, only Kupffer cells （liver resident macrophages） express significant levels of PK2/Bv8 and its receptors, prokineticin receptor 1 and 2.CONCLUSION： In normal liver PK2/Bv8 and its receptors were specifically expressed by Kupffer cells. PK2/Bv8 expression decreased as the liver evolves towards cancer and did not correlate with HCC angiogenesis.

关键词： Prokineticin Hepatocellular carcinoma PK2/Bv8 Angiogenesis Kupffer cells Vascular endothelial growth factor Liver

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Acoustic radiation force impulse imaging for assessing liver fibrosis in alcoholic liver disease

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World Journal of Gastroenterology 2016年第20期22卷 4926-4935页

作者： Anita Kiani Vanessa Brun Fabrice Lainé bruno turlin Jeff Morcet Sophie Michalak Antonia Le Gruyer Ludivine Legros Edouard Bardou-Jacquet Yves Gandon Romain Moirand Department of Abdominal Imaging Rennes University Hospital Clinical Inverstigation Center CIC INSERM 1414 Rennes University Hospital Department of Hepatology Rennes University Hospital Department of Pathology Rennes University Hospital Rennes Department of Pathology Angers University Hospital Department of Addictology Rennes University Hospital Department of Research INSERM UMR 991 Rennes 1 Medicine University

AIM: To evaluate the performance of elastography by ultrasound with acoustic radiation force impulse(ARFI) in determining fibrosis stage in patients with alcoholic liver disease(ALD) undergoing alcoholic detoxification in relation to ***: Eighty-three patients with ALD undergoing detoxification were prospectively enrolled. Each patient underwent ARFI imaging and a liver biopsy onthe same day. Fibrosis was staged according to the METAVIR scoring system. The median of 10 valid ARFI measurements was calculated for each ***: Sixty-nine males and thirteen females(one patient excluded due to insufficient biopsy size) were assessed with a mean alcohol consumption of 132.4 ± 128.8 standard drinks per week and mean cumulative year duration of 17.6 ± 9.5 years. Sensitivity and specificity were respectively 82.4%(0.70-0.95) and 83.3%(0.73-0.94)(AUROC = 0.87) for F ≥ 2 with a cut-off value of 1.63m/s; 82.4%(0.64-1.00) and 78.5%(0.69-0.89)(AUROC = 0.86) for F ≥ 3 with a cut-off value of 1.84m/s; and 92.3%(0.78-1.00] and 81.6%(0.72-0.90)(AUROC = 0.89) for F = 4 with a cut-off value of 1.94 m/***: ARFI is an accurate, non-invasive and easy method for assessing liver fibrosis in patients with ALD undergoing alcoholic detoxification.

关键词： Alcoholic liver disease Elastography Noninvasive Acoustic radiation force impulse Fibrosis

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EGFR Expression Is Unreliable to Decide for Cetuximab Treatment in Patients with Metastatic Colorectal Cancer: Results from “ERBITUX-OUEST”

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Open Journal of Internal Medicine 2016年第2期6卷 56-67页

作者： Jean-Philippe Metges Erick Gamelin Alain Volant Olivier Capitain Jean-François Ramée Jean-Luc Raoul Jean-Yves Douillard Pierre-Luc Etienne Isabelle Cumin Olivier Dupuis Roger Faroux Marie-Aude Coulon Philippe Deguiral Karine Bideau Nacr Eddine Achour Alain Gourlaouen Corinne Alleaume Annie Wdowik Laurent Miglianico Yann Touchefeu Vincent Klein Alain Penchet Ludovic Rosenfeld Daniel Martin Claire Stampfli Jean-Jacques Auger Alain Bargain Murielle Broyer-Petit Jérome Chettrit Louis-Rémi De Ybarlucea Serge Eloit Pierre Marie Girardot Nathalie Heresbach Christian Laboisse Eric Lavoine Gilles Lemasson Claire Magois Sophie Michalak Norbert Padilla Joseph Politis Frédéric Staroz bruno turlin Arnaud Uguen Viorel Vasiliu Véronique Verriele Fanny Marhuenda Delphine Déniel Lagadec Christian Riché Françoise Grudé Observatoire dédié au Cancer des régions Bretagne et Pays de la Loire France Centre Hospitalier Régional Universitaire (CHRU) Brest France Institut de Cancérologie de l’Ouest (ICO) Paul Papin Angers France Centre Catherine de Sienne Nantes France CRLCC Eugène Marquis Rennes France ICO René Gauducheau Nantes France Centre CARIO-HCPA Plérin France Centre Hospitalier Bretagne Sud (CHBS) Lorient France Clinique Victor Hugo Le Mans France Centre Hospitalier Départemental (CHD) La Roche-sur-Yon France CH Le Mans France Clinique Mutualiste de l’Estuaire Saint-Nazaire France CHIC Quimper France Clinique Pasteur Lanroze Brest France CH MORLAIX France CH Saint-Brieuc France CHBA Vannes France CHP Saint-Grégoire France CHU Nantes France Hopital Privé Océane Vannes France Clinique Saint-Michel et Sainte-Anne Quimper France Pole Santé Sarthe et Loire La Flèche France Polyclinique du Maine Laval France Polyclinique Sud Quimper France CH Laval France Polyclinique Cesson Sévigné France Laboratoire d’anatomie et de cytologie pathologiques Cholet France Cabinet d’anatomie et de cytologie pathologiques Saint-Malo France Laboratoire d’anatomie et de cytologie pathologiques Lorient France Institut d’histopathologie Nantes France Laboratoire de Pathologie Médicale Laval France ARMOR Pathologie Plérin France Laboratoire d’anatomie et de cytologie pathologiques Rennes France Laboratoire d’anatomie et de cytologie pathologiques Angers France Laboratoire Analyses Biologie Glasgow Brest France CHU Angers France Centre d’anatomie et de cytologie pathologiques Le Mans France Cabinet d’anatomie et de cytologie pathologiques Vannes France Laboratoire d’anatomie et de cytologie pathologiques Quimper France CHU Rennes France

Purpose: Although controversial, assessment of epidermal growth factor receptor (EGFR) expression is required for the approved indications of Cetuximab in metastatic colorectal cancer (mCRC). With the objective of improving patient selection, “ERBITUX-OUEST” study aimed at analyzing EGFR status in a large cohort of mCRC patients who received cetuximab without preliminary EGFR screening, and assessing the correlation between EGFR status and response to treatment retrospectively. Patients and methods: 332 patients treated with Irinotecan Cetuximab based regimen after progression on irinotecan or oxaliplatin therapy were included. EGFR status was assessed using three available immunohistochemistry (IHC) tests and in situ hybridization in case of negativity. Clinical outcomes of EGFR-positive and EGFR-non-detected (or considered as negative with at least one test) patients were compared. Results: Of the 332 samples centrally screened, 194 were classified as full-positive (i.e., EGFR-positive for all three tests), 86 as full-negative, and 52 as discordant. One third of the 131 negative samples with FDA approved test should be reclassified as positive with at least one of the two others tests. Regarding results from FDA approved test only, neither objective response rate (ORR), progression-free survival (PFS) nor overall survival (OS) differed significantly between EGFR-negative and EGFR-positive patients (P = 0.788, 0.326 and 0.888, respectively). Similarly, comparison of full-negative to other groups did not show any significant difference in terms of ORR (P = 0.507), PFS (P = 0.222) or OS (P = 0.686). Conclusion: These data strongly argue against mCRC patients selection for Cetuximab treatment based on EGFR expression as measured by currently available IHC technics.

关键词： Metastatic Colorectal Cancer Cetuximab EGFR Expression

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