ZAP70 Expression Assessed by Immunohistochemistry on Peripheral Blood: A Simple Prognostic Assay for Patients With Chronic Lymphocytic Leukemia

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ZAP70 Expression Assessed by Immunohistochemistry on Peripheral Blood: A Simple

Prognostic Assay for Patients With Chronic Lymphocytic Leukemia.

Michele Roullet, Sargent, Theresa Pasha, Isabela Cajiao, Elstrom,

Treasa , Liebhaber, Zhang, and Adam Bagg

Appl Immunohistochem Mol Morphol, December 1, 2007; 15(4): 471-476.

Departments of *Pathology and Laboratory Medicine ?Medicine ?Genetics,

University of Pennsylvania School of Medicine, Philadelphia, PA.

The somatic hypermutational (SHM) status of the immunoglobulin heavy-chain

variable (IgVH) gene is a powerful prognostic factor in patients with chronic

lymphocytic leukemia (CLL). However, IgVH SHM analysis is not well-suited to

routine use in the clinical diagnostic laboratory. ZAP70 expression is a

potential surrogate for the absence of SHM. Given the current problems with the

standardization of ZAP70 assessment by flow cytometry, we sought an alternative

approach, using immunohistochemistry (IHC). The utility of IHC is largely

restricted to tissues, precluding its routine application to most patients with

CLL who are typically diagnosed based upon peripheral blood (PB) findings.

Accordingly, we developed an IHC assay that can be performed on PB. Enriched PB

mononuclear cells from 29 patients with CLL were analyzed for ZAP70 expression

by IHC on paraffin-embedded cell blocks, using standard techniques. IgVH SHM

analysis was performed on all cases, and clinical features recorded. Seventeen

specimens (59%) were negative for ZAP70 expression and 12 (41%) were positive

for ZAP70 expression. SHM was evident in 20 specimens (69%), and absent in 9

(31%). Seventy-six percent of the specimens (22/29) displayed " concordant " ZAP70

and SHM results, in that 15 (52%) were SHM-positive/ZAP70 negative, whereas 7

(24%) were SHM-negative/ZAP70 positive. ZAP70 expression in this small cohort

correlated with poor clinical outcome. Importantly, IHC analysis of ZAP70 in PB

is a simple, reliable, robust assay that may have a valuable role in the routine

clinical laboratory assessment of patients with CLL.

PMID: 18091393