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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-25948

Leuenberger, M; Frigerio, S; Wild, P J; Noetzli, F; Korol, D; Zimmermann, D R; Gengler, C; Probst-Hensch, N M; Moch, H; Tinguely, M (2010). AID protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma is associated with poor prognosis and complex genetic alterations. Modern Pathology, 23(2):177-186.

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Abstract

The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P=0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P=0.002) and p53 deletion (P=0.004) were significantly associated with AID. IgV(H) gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P=0.001). Although there was a trend, we could not show an association with the IgV(H) gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV(H) status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor in its transformation.Modern Pathology advance online publication, 6 November 2009; doi:10.1038/modpathol.2009.156.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Social and Preventive Medicine
04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
DDC:610 Medicine & health
Language:English
Date:2010
Deposited On:15 Dec 2009 15:01
Last Modified:22 Jan 2014 04:47
Publisher:Nature Publishing Group
ISSN:0893-3952
Publisher DOI:10.1038/modpathol.2009.156
PubMed ID:19898425
Citations:Web of Science®. Times Cited: 10
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Scopus®. Citation Count: 12

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