CD56, Cyclin D1, p53 and p21 antigen expression in plasma cells as a prognostic factor of chronic kidney disease in 122 bone marrow biopsies cases of multiple myeloma

2018 ◽  
Author(s):  
Jurijs Nazarovs ◽  
Sandra Lejniece
Keyword(s):  
Chronic Kidney Disease ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Factor ◽  
Kidney Disease ◽  
Cyclin D1 ◽  
Plasma Cells ◽  
Antigen Expression ◽  
Bone Marrow Biopsies

Automated digital enumeration of plasma cells in bone marrow trephine biopsies of multiple myeloma

2020 ◽  
pp. jclinpath-2020-207066
Author(s):  
Jacques A J Malherbe ◽  
Kathryn A Fuller ◽  
Bob Mirzai ◽  
Bradley M Augustson ◽  
Wendy N Erber
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Intraclass Correlation ◽  
Antigen Expression ◽  
Bone Marrow Biopsies ◽  
Bone Marrow Trephine ◽  
Bone Marrow Trephine Biopsy ◽  
Plasma Cell Neoplasms

AimsDetermination of the number of plasma cells in bone marrow biopsies is required for the diagnosis and ongoing evaluation of plasma cell neoplasms. We developed an automated digital enumeration platform to assess plasma cells identified by antigen expression in whole bone marrow sections in multiple myeloma, and compared it with manual assessments.MethodsBone marrow trephine biopsy specimens from 91 patients with multiple myeloma at diagnosis, remission and relapse were stained for CD138 and multiple myeloma oncogene 1 (MUM1). Manual assessment and digital quantification were performed for plasma cells in the entire trephine section. Concordance rates between manual and digital methods were evaluated for each antigen by intraclass correlation analyses (ICC) with associated Spearman’s correlations.ResultsThe digital platform counted 16 484–1 118 868 cells and the per cent CD138 and MUM1-positive plasma cells ranged from 0.05% to 93.5%. Overall concordance between digital and manual methods was 0.63 for CD138 and 0.89 for MUM1. Concordance was highest with diffuse plasma cell infiltrates (MUM1: ICC=0.90) and lowest when in microaggregates (CD138: ICC=0.13). Manual counts exceeded digital quantifications for both antigens (CD138: mean=26.4%; MUM1: mean=9.7%). Diagnostic or relapse threshold counts, as determined by CD138 manual assessments, were not reached with digital counting for 16 cases (18%).ConclusionsAutomated digital enumeration of the entire, immunohistochemically stained bone marrow biopsy section can accurately determine plasma cell burden, irrespective of pattern and extent of disease (as low as 0.05%). This increases precision over manual visual assessments which tend to overestimate plasma burden, especially for CD138, and when plasma cells are in clusters.

scholarly journals The Importance of Cyclin D1, P53, Cd56 Antigen Expression in Plasma Cells and its Correlation with Serological and Clinical Parameters in Patients with Multiple Myeloma

2018 ◽  
Vol 72 (5) ◽  
pp. 259-267
Author(s):  
Jurijs Nazarovs ◽  
Regīna Kleina ◽  
Sandra Lejniece
Keyword(s):  
Multiple Myeloma ◽  
Cyclin D1 ◽  
Plasma Cells ◽  
Osteolytic Lesion ◽  
Antigen Expression ◽  
High Serum ◽  
Bone Marrow Biopsies ◽  
Low Platelet Count ◽  
Cd56 Expression ◽  
Cd56 Antigen

Abstract CD56, p53, and Cyclin D1 detection in plasma cells (PC) can help to predict prognosis of multiple myeloma (MM). Clinical and biochemical prognostic parameters were analysed in a group of 122 patients with primary diagnosed MM in the period 2011–2015. Bone marrow biopsies were analysed with Cyclin D1, p53, CD56 antibodies. Statistical analysis was performed using Microsoft Excel 2010 and Graph Pad Prism 5. Lack of CD56 expression and p53-positivity were significantly correlated with a low glomerular filtration rate (GFR), low platelet count and haemoglobin level, as well as with high serum creatinine levels. Patients with Cyclin D1 expression in PC had a significantly higher serum calcium level and more common osteolytic lesion in bones. CD56-negative as well as p53, Cyclin D1-positive groups had advanced Salmon–Durie MM stages by and significantly higher ß2-microglobulin. Expression of p53, Cyclin D1 and lack of CD56 antigen in PC are negative predictive factors in cases of MM, as these patients were diagnosed as having late Salmon–Durie stage and higher ß2-microglobulin level. Expression of p53 and lack of CD56 antigen in PC is associated with an increased creatinine level in blood and decreased GFR; therefore, these are criteria for chronic renal failure progression and poorer prognosis of MM.

scholarly journals Increased expression of cyclin-D1 on trephine bone marrow biopsies independently predicts for shorter overall survival in patients with multiple myeloma treated with novel agents

2012 ◽  
Vol 87 (7) ◽  
pp. 734-736 ◽  
Author(s):  
Anna Tasidou ◽  
Maria Roussou ◽  
Evangelos Terpos ◽  
Efstathios Kastritis ◽  
Maria Gkotzamanidou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Cyclin D1 ◽  
Novel Agents ◽  
Bone Marrow Biopsies

CD28-Mediated Regulation of Multiple Myeloma Cell Proliferation and Survival.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 355-355
Author(s):  
Kelvin P. Lee ◽  
Nizar J. Bahlis ◽  
Anne M. King ◽  
Despina Kolonias ◽  
Louise M. Carlson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
T Cells ◽  
Cell Survival ◽  
Plasma Cells ◽  
Survival Function ◽  
Myeloma Cell ◽  
Serum Starvation ◽  
Bone Marrow Biopsies

Abstract Although interactions with bone marrow stromal cells are essential for multiple myeloma (MM) cell survival, the specific molecular and cellular elements involved are largely unknown due to the complexity of the bone marrow microenvironment. The CD28 receptor, which costimulates survival signals in T cells, is also expressed on normal plasma cells and myeloma cells. In MM, CD28 expression correlates significantly with disease progression, also suggesting a pro-survival function. In contrast to T cells however, activation and function of CD28 in myeloma and plasma cells is almost entirely undefined. We found that direct activation of myeloma cell CD28 by anti-CD28 mAb alone induced activation of NFkappaB, suppressed MM cell proliferation and protected against serum starvation and dexamethasone-induced cell death. We hypothesized that the specific CD80/CD86 expressing stromal cell partner of this interaction is a professional antigen presenting cells, in particular dendritic cells. Histological studies demonstrated DC were extensively interdigitated throughout the myeloma infiltrates in patient bone marrow biopsies. In vitro coculture with DC also elicited CD28-mediated effects on MM survival and proliferation, and could be blocked by CD28Ig. Our findings suggest a previously undescribed myeloma:DC cell-cell interaction involving CD28 that may play an important role in myeloma cell survival within the bone marrow stroma. These data also suggest that CD28 may represent a therapeutic target in the treatment of multiple myeloma.

Increased Expression of Cyclin-D1 on Trephine Bone Marrow Biopsies Independently Predicts for Shorter Overall Survival In Patients with Multiple Myeloma Treated with Novel Agents

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2965-2965
Author(s):  
Evangelos Terpos ◽  
Maria Roussou ◽  
Anna Tasidou ◽  
Magdalini Migkou ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Cyclin D1 ◽  
Plasma Cells ◽  
Univariate Analysis ◽  
Novel Agents ◽  
Positive Staining ◽  
Newly Diagnosed ◽  
Immunohistochemical Expression

Abstract Abstract 2965 The cyclin-D1 proto-oncogene is an important cell regulator of G1 to S phase progression. The overexpression of cyclin-D1 has been linked to the development and progression of several malignancies. The aim of our study was to evaluate the impact of the immunohistochemical expression of cyclin-D1on the plasma cells of trephine biopsies on survival of newly-diagnosed patients with multiple myeloma (MM) who were treated with novel agents. We evaluated formalin-fixed, paraffin-embedded, bone marrow sections of 130 consecutive patients with newly-diagnosed MM (67M/63F; median age 68 years) before any kind of therapy administration. One hundred and fifteen patients had symptomatic disease that required therapy: 29 (25%) received bortezomib-based regimens and 31 (26%) received thalidomide-based regimens as first line therapy, while all patients received regimens containing bortezomib or an IMiD at some point during the course of their disease. Immunohistochemistry was performed in all trephine biopsies using monoclonal antibodies against cyclin-D1 (Cell Marque Corp., Rocklin, CA, USA), but also against CD56 (Cell Marque Corp., Rocklin, CA, USA), CD27 (Novocastra, Newcastle upon Tyne, UK), CD117 and MUM-1 (DAKO A/S, Glostrup, Denmark), as recommended by the manufacturers. A case was considered positive if there was unequivocal positive staining of at least 20% of the plasma cells for cyclin-D1, CD56 and MUM-1 and a positive staining of at least 10% of the plasma cells for CD117 and CD27. Among patients with symptomatic myeloma (N=115), positive staining for cyclin-D1 was found in 35 (30%) patients, for CD56 in 45 (39%), for CD117 in 94 (81%) and for CD27 in 72 (62%) patients. In patients with asymptomatic myeloma, positive staining for Cyclin-D1 was found only in 1 (7%) patient, for CD56 in 9 (64%), and for CD117 in 6 (43%) (p<0.01 for all comparisons compared to symptomatic patients). There were significant positive correlations between positivity for CD27 and CD56 (p<0.001), between positivity for cyclin-D1 and CD117 (p=0.045) and a negative correlation between positivity for CD117 and CD56 (p=0.001). We also observed significant correlations between CD56 positivity and ISS-1 or ISS-2 (p=0.01) and between CD117 positivity and ISS-3 disease (p=0.002). The median overall survival (OS) for patients with symptomatic MM was 57 months (range 22–120 months). In the univariate analysis, positivity for cyclin-D1 (41 vs. 62 months, p=0.03) and for CD117 (50 vs. 75 months p=0.018) were associated with inferior survival, while positivity for CD56 (47 vs. 62 months, p=0.286), MUM-1 (52.7 vs. 63.8 months, p=0.528) and CD27 (57 vs. 50 months, p=0.445) were not. Other factors associated with inferior OS, in the univariate analysis, included ISS-3 (median OS 37 months, vs. 57 months for ISS-2 and 73 months for ISS-1, p=0.005), Hb <10 g/dl (56 vs. 73 months, p=0.044), corrected serum calcium >11.5 g/dl (29 vs. 62 months, p=0.02), serum LDH above upper normal limit (31 vs. 61 months, p=0.05), serum creatinine >2 mg/dl (26 vs. 64 months, p=0.007), low platelet counts (<100,000/ml) (22 vs. 62 months, p=0.031) and age >65 years (45 months vs. not reached for younger patients, p=0.002). In the multivariate analysis, positivity for cyclin-D1 (HR: 2.6; p=0.001), ISS stage (HR: 1.8; p=0.001) and age >65 (HR 2.7, p=0.003) were independently associated with inferior survival. Immunohistochemistry for cyclin-D1 identified subgroups of patients in ISS-2 and in ISS-3 who had extremely poor outcome. Patients with cyclin-D1 positivity had a median survival of 22 months in ISS-2 (vs. 64 months for the rest of ISS-2 patients, p=0.01) and of 13 months in ISS-3 (vs. 47 months for the rest of ISS-3, p=0.012). Our findings underline that the immunohistochemical expression of cyclin-D1 in the bone marrow trephine biopsies has independent prognostic value in MM patients, even in the era of novel agents. This marker can easily be assessed in patients who undergo a trephine biopsy as part of their initial evaluation and offers significant prognostic information. Furthermore, novel agents targeting cyclin-D1 may be of therapeutic value in MM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CD43 Expression Is an Adverse Prognostic Factor in Newly Diagnosed Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4753-4753
Author(s):  
Xueqin Ning ◽  
Yongqiang Wei ◽  
Xiaolei Wei ◽  
Ru Feng ◽  
Bingyuan Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Factor ◽  
Plasma Cells ◽  
Newly Diagnosed ◽  
Negative Group ◽  
Hematopoietic Stem ◽  
Female Ratio ◽  
Positive Group ◽  
Adverse Prognostic Factor

Abstract CD43 expression is an adverse prognostic factor in newly diagnosed multiple myeloma Introduction CD43 is an abundant, heavily-glycosylated, cell surface protein expressed on bone marrow hematopoietic stem cells and most white blood cells. Previous studies have found that CD43 also expressed in some types of lymphoma cells and associated with adverse outcomes. However, the prognosis value of CD43 expression in multiple myeloma (MM) remain unknown. Patients and Methods A total of 109 MM patients, newly diagnosed in Nanfang Hospital of Southern Medical University from January 2017 to December 2019, were included in the study. CD43 was detected by flow cytometre as follows: 2 ml of heparin anticoagulated bone marrow was collected from the patients at the time of diagnosis，1×10 6 cells were detected, and a gate was set for identifying abnormal plasma cells characterized by CD138 expression and CD38. CD43 positive was defined as more than 20% of the plasma cells expressed CD43. Results A total of 109 patients with newly diagnosed MM were enrolled in the study, including 77 patients (70.6%) for CD43 positive and 32 patients (29.4%) for CD43 negative . The median age was 58 years, and the male-female ratio was 1.7:1. Patients in the CD43 positive group were more likely to have international staging system (ISS) stage III (67.5% VS 46.9%, P= 0.044), hemoglobin &lt; 85g/L (64.9% VS 37.5%, P= 0.008), 13q deletion (31.4% VS 10.4%), and higher percentage of bone marrow monoclonal plasma cells detected by flow cytometry (5.5% VS 1.4%, P=0.003). Most patients enrolled in the study received bortezomib-based treatment. The very good partial response (VGPR) or better rate after 4 induction cycles was significantly lower in the CD43 positive group than CD43 negative group (35.1% VS 56.3%, P=0.041), and the overall response rate (ORR) in the CD43 positive group was lower than that in CD43 negative group (75.3% VS 84.4%, P=0.299), but no significantly difference. The median follow-up time was 22 months. Patients with CD43 positive had significantly lower PFS (median PFS 24 months VS not reached, P =0.012), and OS (median OS not reached, P = 0.023) than those with CD43 negative. Multivariate analysis indicated that CD43 positive expression was an independent poor risk factor for PFS (HR 2.517 95%CI 1.178-5.376, P = 0.017) and OS (HR 3.664 95%CI 1.100-12.075, P = 0.034). Conclusion Our study showed that CD43 expression was an adverse prognosis for multiple myeloma. Disclosures No relevant conflicts of interest to declare.

Observations On Eosinophil Ifiltrates in The Bone Marrow Of Patients With Multiple Myeloma. Clinicopathological Correlates

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5338-5338
Author(s):  
Finella MC Brito-Babapulle ◽  
Tanya Cranfield ◽  
Robert B Corser ◽  
Helen Dignum ◽  
Christopher James ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Osteolytic Lesion ◽  
Inverse Correlation ◽  
Eosinophil Infiltration ◽  
Bone Marrow Biopsies ◽  
Lytic Lesions

Abstract Mouse eosinophils have been shown in 2011 to be required for the maintenance of long lasting plasma cells in the bone marrow and in maintaining the bone marrow plasma cell microenvironment. Human eosinophils have been shown by Wong et al to support multiple myeloma cell proliferation via a mechanism independent of IL6. We looked at bone marrow biopsies taken from patients who had a paraprotein and in whom a diagnosis of multiple myeloma was suspected. These samples were taken solely for the purposes of diagnosisng multiple myeloma and were retrospectively reviewed from the point of view of degree of eosinophil infiltration and its correlation with tumour load, bone lytic lesions, plasma cell morphology, whether blastic, crystalline inclusions, Mott cells, flame cells and or lymphoplasmacytoid. There were no cases of IGD or E myeloma or osteosclerotic myeloma.Nonsecretory myeloma and cases of light chain myeloma with or without amyloid were included in the series. Biopsies were not performed from osteolytic lesion unless biopsy was necessary to make a diagnosis of myeloma. Myeloma was diagnosed when plasma cell infiltrate was greater than 10% on bone marrow aspirate with a paraprotein and or lytic lesions. Eosinophil infiltration did not correlate with any of the tumour clinicopathological markers but showed an inverse correlation with degree of plasmacytosis. Eosinophils were hardly ever found in marrow aspirates that had over 70% plasma cells. They were usually found in trephine sections of bone marrow in areas where there was Grade I/II fibrosis and were often found in close proximity to focal areas of plasma cell infiltration. Whether eosinophils play a role in preventing or maintaining malignant plasma cell recurrence is currently being studied. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Is There Any Relationship between Human Herpesvirus-8 and Multiple Myeloma?

Lymphoma ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Mohammad Hadi Sadeghian ◽  
Maryam Mohammadnia Avval ◽  
Hossein Ayatollahi ◽  
Mohammad Reza Keramati ◽  
Bahram Memar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Human Herpesvirus ◽  
The Body ◽  
Human Herpesvirus 8 ◽  
Bone Marrow Biopsies ◽  
Exact Test ◽  
Herpesvirus 8

Background. Human herpesvirus-8 (HHV-8) is associated with some human diseases including Kaposi’s sarcoma and also some B-cell lymphoproliferative disorders. Few studies have highlighted the potential role of HHV-8 in the development of multiple myeloma (MM) which is known as a malignant proliferation of plasma cells derived from a single clone. Aims. The aim of this study was to find a relationship between HHV-8 and MM using polymerase chain reaction (PCR) method. Materials and Methods. This study was conducted on 30 formalin-fixed, paraffin-embedded (FFPE) bone marrow biopsies of multiple myeloma and 30 normal FFPE bone marrow biopsies. After the sample preparation, Deoxyribonucleic acid (DNA) was extracted by nonheating procedure. PCR for HHV-8 virus was carried out with commercial kit and the PCR products were visualized by gel electrophoresis. Finally, the statistical analysis was performed. Results. HHV-8 virus was not detected by PCR from FFPE blocks of multiple myeloma samples, while only one of the controls showed DNA band of the corrected molecular weights. Fisher’s exact test showed that no statistical differences were found between the two groups (P=0.999). Conclusion. Our report adds to the body of evidence that there is no association between HHV- 8 and MM against a major role of HHV-8 infection in the pathogenesis of clonal plasma cell proliferation.

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