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Originally published online as doi:10.2353/ajpath.2009.080647 on February 26, 2009

Published online before print February 26, 2009
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(American Journal of Pathology. 2009;174:1160-1171.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080647

Specific Detection of CD56 (NCAM) Isoforms for the Identification of Aggressive Malignant Neoplasms with Progressive Development

Stefan Gattenlöhner*, Thorsten Stühmer{dagger}, Ellen Leich*, Matthias Reinhard{ddagger}, Benjamin Etschmann*, Hans-Ulrich Völker*, Andreas Rosenwald*, Edgar Serfling*, Ralf Christian Bargou{dagger}, Georg Ertl§, Hermann Einsele{dagger} and Hans-Konrad Müller-Hermelink*

From the Institutes of Pathology,* and Internal Medicine II,{dagger} and the Department of Internal Medicine I,§ University of Würzburg, Würzburg; and immunoGlobe Antikoerpertechnik GmbH,{ddagger} Himmelstadt, Germany

Alternative splicing of transcripts from many cancer-associated genes is believed to play a major role in carcinogenesis as well as in tumor progression. Alternative splicing of one such gene, the neural cell adhesion molecule CD56 (NCAM), impacts the progression, inadequate therapeutic response, and reduced total survival of patients who suffer from numerous malignant neoplasms. Although previous investigations have determined that CD56 exists in three major isoforms (CD56120kD, CD56140kD, and CD56180kD) with individual structural and functional properties, neither the expression profiles nor the functional relevance of these isoforms in malignant tumors have been consistently investigated. Using new quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) strategies and novel CD56 isoform-specific antibodies, CD56140kD was shown to be exclusively expressed in a number of highly malignant CD56+ neoplasms and was associated with the progression of CD56+ precursor lesions of unclear malignant potential. Moreover, only CD56140kD induced antiapoptotic/proliferative pathways and specifically phosphorylated calcium-dependent kinases that are relevant for tumorigenesis. We conclude, therefore, that the specific detection of CD56 isoforms will help to elucidate their individual functions in the pathogenesis and progression of malignant neoplasms and may have a positive impact on the development of CD56-based immunotherapeutic strategies.







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