Apoptosis in human colorectal tumours: ultrastructure and quantitative studies on tissue localization and association with bak expression |
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Authors: | Gerda Partik Patrizia Kahl-Rainer Roland Sedivy Adolf Ellinger Wilfried Bursch B. Marian |
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Affiliation: | (1) Institute of Tumour Biology – Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria e-mail: brigitte.marian@univie.ac.at Tel.: (43) 1-401 54/234, Fax: (43) 1-406 0790, AT;(2) Institute of Clinical Pathology, University of Vienna, Vienna, Austria, AT;(3) Institute of Histology and Embryology, University of Vienna, Vienna, Austria, AT |
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Abstract: | Apoptotic cell death in human tumours has been demonstrated by electron and light microscopy. In adenomas, fragmented and apoptotic nuclei and signs of phagocytosis have been observed close to the basement membrane. In carcinomas the characteristic structures were apoptotic bodies with small fragments of chromatin. DNA fragmentation was shown by in situ end-labelling. Quantitative assessment of apoptosis and proliferation revealed a high apoptotic index (AI) in all types of adenoma (tubular: 1.77±0.35%, tubulovillous: 2.38± 0.41%; villous: 3.3±0.39%) as well as loss of compartmentalization of proliferating and dying cells. In carcinomas a shift towards proliferation was evident, as shown by lower AIs than in adenomas (0.9±0.68% and 1.1±0.12% for moderately and poorly differentiated tumours), higher Ki67 indices (38.32±2.23% and 57± 3.89%, respectively) and higher mitosis (0.9±0.56% and 1.21±0.17%, respectively). However, apoptosis was observed in all tumours and is available as a target for therapeutic intervention. Expression of the apoptosis related proteins bcl-2 and bak also reflected loss of compartmentalization. While bcl-2 did not show a consistent relationship to AI in tumour specimens, bak was positively correlated with apoptosis in 4 of 8 adenomas and 4 of 7 carcinomas, suggesting a role for this protein in the induction of apoptosis in a subset of tumours. Received: 22 July 1997 / Accepted: 27 October 1997 |
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Keywords: | Apoptosis bcl-2 bak Colorectal carcinogenesis |
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