CD177 (NB1) Expression on Neutrophils; in Search of a Kappa/Lambda Ratio for Myeloid Clonality
Howard Meyerson, Anna Balog. University Hospitals Case Medical Center, Cleveland, OH
Background: Currently there is no simple method to determine clonality on non-lymphoid cells by flow cytometry akin to the B cell kappa/lambda ratio. CD177 (NB1) has bimodal expression on mature neutrophils with only a portion of neutrophils CD177 positive. We hypothesized that the fraction of CD177(+) neutrophils might be altered in a clonal myeloid process similar to a skewed kappa/lambda ratio for B cells and could be used to identify myeloid neoplasia.
Design: 98 control samples were evaluated to determine the normal range of expression of CD177. Subsequently an additional 235 blood and bone marrow samples were prospectively evaluated for the percentage of CD177 expressed on CD16(+) neutrophils (PMNs) by flow cytometry. The data set included 96 myeloid neoplasms (41 AML, 21 MDS, 12 Jak2-associated MPDs, 5 CMML, 4 CML and 13 other myeloid processes) and 139 specimens with benign disorders.
Results: The mean portion of CD177(+) PMNs in control samples was 65.9% +/-25.4 with 91% of controls having more than 40% CD177(+) PMNs and 94% having more than 30% CD177(+) PMNs. Expression in controls was skewed toward the high end as 11% of samples contained greater than 90% and 6% more than 95% CD177(+) PMNs. Based on this data, a prospective study of 235 samples was performed to evaluate for expression of CD177 outside these values on routine specimens sent to the flow cytometry laboratory. Skewed low expression of CD177 was statistically associated with myeloid neoplasia at values less than 40%. The portion of patients with a myeloid neoplasm with CD177(+) PMNs less than 40% and 30% was 38% (36/96) and 26% (25/96) compared to 16% (20/129) and 5% (7/129) of patients with a non-neoplastic condition (p values of 0.0002 and 0.00002 respectively). The overall specificity of low CD177 for myeloid malignancy was 84% with a PPV of 64% and NPV of 64% using a 40% cutoff or 95%, 78% and 63% using a 30% cut-off. No differences were observed between groups at the high end of CD177 expression (>90%, 95% or 98%). For low CD177, findings were most pronounced in MDS and CMML with 52% (11/21) of MDS containing less than 40% and 38% (8/21) containing less than 30% CD177(+) PMNs. All 5 CMML samples had low CD177.
Conclusions: Skewed low CD177 expression on PMNs is highly associated with myeloid neoplasia, particularly MDS and CMML, and is useful for the detection of a myeloid neoplasm in a portion of cases. However, skewed high CD177 expression is not associated with neoplasia as might be expected for a molecule demonstrating clonal allelic expression similar to immunoglobulin light chains.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 213, Wednesday Afternoon