Expression Patterns of Aberrant Antigens on Neoplastic Plasma Cells and Their Association with CKS1B Positive Cytogenetic Subgroup
Shouying Du, Sherrie L Perkins, Andrew Wilson, Sarah South, Reha M Toydemir, David W Bahler, Mohamed E Salama. ARUP Laboratories, University of Utah, Salt Lake City, UT
Background: Plasma cell neoplasms (PCNs) are subclassified into several prognostic subgroups based on the cytogenetics. Little is known about antigen expression pattern and its association with cytogenetic aberrations. CKS1B is a new cytogenetic marker associated with poor outcome. We examined the correlation between immunophenotype and cytogenetics to identify trends or possible surrogate markers for genetic abnormalities, particularly in the CKS1B subgroup.
Design: Retrospective review of 1633 consecutive bone marrow samples from our data files identified 457 specimens (from 284 patients with PCNs). 167 bone marrow specimens had informative concurrent positive immunophenotypic and cytogenetics data. Flow cytometry analysis included CD138, Kappa, Lambda, CD19, CD20, CD56, CD54, CD52, CD117 & CD45. FISH analysis included probes for CKS1B, CCND1, IGH, ASS, PML, TP53, RARA, FGFR3 and MAF. Statistical analysis was perfomed using Fisher's exact and Cochran-Armitage trend test.
Results: CD19, CD20, CD52, CD56, and CD117 are variably expressed on PCNs subgroups. As reported, the coexpression of CD56 and CD117 is positively associated with gain of ASS1 and PML. However, in contrast to published data indicating that CCND1/IgH rearrangement is almost exclusively present in CD56+CD117- PCNs, our study reveals that IgH rearrangent, especially CCND1/IgH rearrangement, is associated with double negativity for CD56 and CD117. Higher expression of CD52 & CD56 but lower expression of CD20 & CD117 is found in the CKS1B positive group (Table 1). CKS1B gain is not associated with CD19 expression. CKS1B copy number showed positive correlation with CD52 (p=0.0065) and CD56 (p=0.25) but negative correlation with CD20 (p=0.0207) and CD117 (p=0.137) when cases with 3 or more CKS1B signals were evaluated. A statistically significant trend was noted with both CD20 (p= 0.0491, Trend = -.07439) and CD52 (p= 0.0018, Trend = 0.11036).
|Immunophenotype (percentage, %)|
|CKS1B + (n=72)||65.30||29.2||2.80||9.7||20.8|
|CKS1B > 3 copies (n=30)||70.0||23.0||3.3||16.7||30.0|