J Korean Med Sci.  2013 Apr;28(4):542-549. 10.3346/jkms.2013.28.4.542.

Immunophenotypic Characterization and Quantification of Neoplastic Bone Marrow Plasma Cells by Multiparametric Flow Cytometry and Its Clinical Significance in Korean Myeloma Patients

• Cho YU
• Park CJ
• Park SJ
• Chi HS
• Jang S
• Park SH
• Seo EJ
• Yoon DH
• Lee JH
• Suh C

• KMID: 1786961
• DOI: http://doi.org/10.3346/jkms.2013.28.4.542

Abstract

Multiparametric flow cytometry (MFC) allows discrimination between normal and neoplastic plasma cells (NeoPCs) within the bone marrow plasma cell (BMPC) compartment. This study sought to characterize immunophenotypes and quantitate the proportion of NeoPCs in BMPCs to diagnose plasma cell myeoma (PCM) and evaluate the prognostic impact of this method. We analyzed the MFC data of the bone marrow aspirates of 76 patients with PCM and 33 patients with reactive plasmacytosis. MFC analysis was performed using three combinations: CD38/CD138/-/CD45; CD56/CD20/CD138/CD19; and CD27/CD28/CD138/CD117. The plasma cells of patients with reactive plasmacytosis demonstrated normal immunophenotypic patterns. Aberrant marker expression was observed in NeoPCs, with negative CD19 expression observed in 100% of cases, CD56+ in 73.7%, CD117+ in 15.2%, CD27- in 10.5%, CD20+ in 9.2%, and CD28+ in 1.3%. In PCM patients, more than 20% of NeoPCs/BMPCs were significantly associated with factors suggestive of poor clinical outcomes. Patients who were CD27- or CD56+/CD27-, demonstrated shorter overall survival than patients of other CD56/CD27 combinations. Our results support the clinical value of immunophenotyping and quantifying NeoPCs in PCM patients. This strategy could help to reveal poor prognostic categories and delineate surrogate markers for risk stratification in PCM patients.

Keyword

Multiple Myeloma; Flow Cytometry; Immunophenotyping; Neoplastic Cells; Plasma Cells

MeSH Terms

Adult
Aged
Aged, 80 and over
Antigens, CD27/metabolism
Antigens, CD56/metabolism
Asian Continental Ancestry Group
Bone Marrow Cells/*cytology/metabolism
Female
Flow Cytometry
Humans
*Immunophenotyping
Kaplan-Meier Estimate
Male
Middle Aged
Multiple Myeloma/metabolism/mortality/*pathology
Neoplasm Staging
Neoplastic Stem Cells/*cytology/metabolism
Prognosis
Republic of Korea
Risk Factors
Antigens, CD27
Antigens, CD56

Figure

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  Fig. 1 Gating strategy for the identification and quantification of neoplastic plasma cells. Plasma cells were gated based on low side scatter and the expression of CD138. Neoplastic plasma cells were characterized as CD56+, CD19-, and CD45weak or -.

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  Fig. 2 Frequencies of aberrant plasma cell immunophenotypes in patients with plasma cell myeloma (PCM). Patients with PCM demonstrated aberrant immunophenotypes in their plasma cells to varying degrees, while all patients with reactive plasmacytosis demonstrated plasma cells with normal immunophenotypes (CD138+, CD19+, CD45+, CD27+, CD56-, and CD20-).

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  Fig. 3 Median overall survival (OS) times of the patients with plasma cell myeloma. The Kaplan-Meier curve demonstrates the differences in the OS rates of two groups of patients, as defined by the expression of CD56 (A) and CD27 (B). The Kaplan-Meier curve also demonstrates the difference in the OS rates between the two groups of patients, as defined by the combined expression of CD56 and CD27. Note the intermediate survival times of patients with intermediate expression patterns (C).

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