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(American Journal of Pathology. 2001;158:1289-1299.)
© 2001 American Society for Investigative Pathology

Regular Articles

c-Myb and Bcl-x Overexpression Predicts Poor Prognosis in Colorectal Cancer

Clinical and Experimental Findings

Annamaria Biroccio*, Barbara Benassi*, Igea D’Agnano*, Carmen D’Angelo*, Simonetta Buglioni{dagger}, Marcella Mottolese{dagger}, Andrea Ricciotti{ddagger}, Gennaro Citro*, Maurizio Cosimelli{ddagger}, Robert G. Ramsay§, Bruno Calabretta¶|| and Gabriella Zupi*

From the Experimental Chemotherapy Laboratory,*
the Pathology Department,{dagger}
and the Surgical Department,{ddagger}
Regina Elena Cancer Institute, Rome, Italy; the Peter MacCallum Cancer Institute,§
Melbourne, Australia; the Department of Microbiology and Immunology,
Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania; and the Department of Biomedical Science,||
University of Modena, Modena, Italy

The aim of this study was twofold: to assess the relationship between c-Myb and Bcl-x expression and to evaluate the prognostic significance of their expression in colorectal carcinoma (CRC) patients. Analysis of tumors from 91 CRC patients for expression of c-Myb and Bcl-x revealed a significant relationship between these two proteins. Kaplan-Meier’s analysis showed an increased risk of relapse and death in patients whose tumor specimens displayed high c-Myb levels and Bcl-x positivity. Similar results were also observed excluding Dukes’ D patients. Molecular analysis using three c-Myb-overexpressing LoVo clones indicated that c-Myb overexpression was accompanied by up-regulation of Bcl-xL protein and mRNA. Tumors originating from these clones injected in nude mice were significantly larger than those formed in mice injected with parental or vector-transfected LoVo cells. Moreover, tumors derived from parental and control vector-transfected but not from c-Myb-overexpressing LoVo cells showed high frequency of apoptotic cells. These results provide direct evidence of an association between c-Myb and Bcl-x expression and suggest that expression of both molecules might be a useful prognostic marker in CRC.




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