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Proliferation kinetics and prognosis in gastric cancer after resection
Authors:Sendler A  Gilbertz K P  Becker I  Mueller J  Berger U  Fink U  van Beuningen D  Siewert J R
Institution:1. Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 München, Germany;2. Institut für Radiobiologie, Sanitätsakademie der Bundeswehr, Neuherbergstr. 11, 80937 München, Germany;3. Institut für Allgemeine Pathologie und Pathologische Anatomie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 München, Germany;4. Department of Pathology, Brigham & Women''s Hospital, 75 Francis Street, Boston, MA 02115, USA;5. Institut für Medizinische Statistik und Epidemiologie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 München, Germany;1. Rouen University Hospital, Department of Digestive Surgery, 1, rue de Germont, 76031 Rouen cedex, France;2. Normandie University, UNIROUEN, UMR 1245 Inserm, Rouen University Hospital, Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, 76000 Rouen, France;3. Rouen University Hospital, Department of Digestive Oncology, 1, rue de Germont, 76031 Rouen cedex, France;4. Department of General and Digestive Surgery, Hautepierre Hospital, Strasbourg University Hospital, 67200 Strasbourg, France;5. Department of digestive surgery, CHU Clermont-Ferrand, 63003 Clermont-Ferrand, France;6. Université de Paris, UMR 1275 CAP Paris-Tech, 75010 Paris, France;7. Service de chirurgie digestive et cancérologique Hôpital Lariboisière, 2, rue Ambroise Paré, 75010 Paris, France;1. Division of Gastroenterology, American University of Beirut Medical Center, P.O. Box 11-0236/16-B, Beirut, Lebanon;2. Department of Pathology & Laboratory Medicine, American University of Beirut Medical Center, PO Box 11-0236, Riad El Solh 11072020, Beirut, Lebanon;1. Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, University of Alcala, Spain;2. Gastroenterology department, Hospital Universitario de Salamanca, University of Salamanca, IBSAL, Spain;3. Department of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, Spain;4. Gastroenterology Unit, Hospital Universitario de Cabueñes, Spain;5. Department of Pathology, Hospital Universitario Ramón y Cajal, University of Alcala, Spain;6. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS),Spain;7. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Spain;1. Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan;2. Division of Surgery, Keio University School of Medicine, Tokyo, Japan
Abstract:The influence of proliferation and proliferation kinetics on prognosis in gastric cancer after complete resection are controversial. In a prospective study we investigated the tumour specimens of 111 patients after resection of gastric cancer, who received 200 mg intravenous (i.v.) bromodeoxyuridine (BrdU) pre-operatively. The following biological parameters were analysed in the tumour tissue using flow-cytometry: DNA ploidy, proportion of S-phase cells, BrdU labelling index (LI), DNA synthesis time (T(s)), potential tumour doubling time (T(pot)), proliferating cell nuclear antigen (PCNA) and Ki-67 LI. The median follow-up time was 40 months (range 19-62 months). Besides the established pathohistological prognostic factors, univariate analysis revealed a prognostic influence on survival for BrdU LI, T(pot) and the proportion of S-phase cells. By multivariate Cox analysis of the completely resected cases, only tumour stage and T(pot) had a significant, independent influence on survival. By classification and regression trees (CART) analysis, resection status, tumour stage and T(pot) defined risk groups with significantly different outcomes. A short T(pot) was a predictor of better survival in stage I, II and IIIA tumours. Ploidy and the other investigated proliferation-related parameters failed to demonstrate any influence on prognosis after resection of gastric cancer.
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