Journal of Pathology and Translational Medicine

Original Articles

Expression of CD99 in Multiple Myeloma: A Clinicopathologic and Immunohistochemical Study of 170 Cases: Su-Jin Shin, Hyangsin Lee, Geunyoung Jung, Minchan Gil, Hosub Park, Young Soo Park, Dok Hyun Yoon, Cheolwon Suh, Chan-Jeoung Park, Jooryung Huh, Chan-Sik Park; Korean J Pathol. 2014;48(3):209-216. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.209

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Background

Multiple myeloma (MM) is a heterogeneous and ultimately fatal disease. Risk stratification using prognostic biomarkers is crucial to individualize treatments. We sought to investigate the role of CD99, a transmembrane protein highly expressed in many hematopoietic cells including subpopulations of normal and neoplastic plasma cells, for MM risk stratification.

Methods

CD99 expression was measured in paraffin samples of bone marrow and extramedullary biopsies of 170 patients with MM. Patients were divided into those with high score (moderately and strongly positive) and low score (negative and weakly positive), with all staining being cytoplasmic and/or membranous.

Results

High anti-CD99 immunostaining was observed in 72 of 136 (52.9%) bone marrow biopsies and 24 of 87 (27.6%) extramedullary biopsies in MM. High CD99 expression of extramedullary specimens was associated with significantly longer overall survival (OS; p=.016). High CD99 expression of extramedullary specimens was also associated with better prognosis in the nonautologous stem cell transplantation group of MM patients (p=.044). In multivariate analysis, International Staging System stage was an independent prognostic factor, whereas CD99 expression was no longer statistically significant.

Conclusions

Expression of CD99 in extramedullary specimens was correlated with longer OS, suggesting that CD99 may be a helpful immunohistochemical marker for risk stratification.

Citations

Citations to this article as recorded by

Cell Adhesion Molecule CD99 in Cancer Immunotherapy
Feng Yu, Guodong Liu, Hailing Zhang, Xiaoyan Wang, Zhi Wu, Qinggang Xu, Yan Wu, Dongfeng Chen
Current Molecular Medicine.2023; 23(10): 1028. CrossRef
Detection of Circulating Tumor Plasma Cells in Monoclonal Gammopathies: Methods, Pathogenic Role, and Clinical Implications
Luzalba Sanoja-Flores, Juan Flores-Montero, Martín Pérez-Andrés, Noemí Puig, Alberto Orfao
Cancers.2020; 12(6): 1499. CrossRef
Tumor suppressor CD99 is downregulated in plasma cell neoplasms lacking CCND1 translocation and distinguishes neoplastic from normal plasma cells and B-cell lymphomas with plasmacytic differentiation from primary plasma cell neoplasms
Qi Gao, Venkata Yellapantula, Maly Fenelus, Janine Pichardo, Lu Wang, Ola Landgren, Ahmet Dogan, Mikhail Roshal
Modern Pathology.2018; 31(6): 881. CrossRef
EWSR1 fusion proteins mediate PAX7 expression in Ewing sarcoma
Gregory W Charville, Wei-Lien Wang, Davis R Ingram, Angshumoy Roy, Dafydd Thomas, Rajiv M Patel, Jason L Hornick, Matt van de Rijn, Alexander J Lazar
Modern Pathology.2017; 30(9): 1312. CrossRef
Activation of the polycomb repressive complex pathway in the bone marrow resident cells of diffuse large B-cell lymphoma patients
Eun Ji Oh, Eun Kyung Kim, Woo Ick Yang, Sun Och Yoon
Leukemia & Lymphoma.2016; 57(8): 1921. CrossRef
CD99 Is Strongly Expressed in Basal Cells of the Normal Adult Epidermis and Some Subpopulations of Appendages: Comparison with Developing Fetal Skin
Gawon Choi, Jin Roh, Chan-Sik Park
Journal of Pathology and Translational Medicine.2016; 50(5): 361. CrossRef
Towards Stratified Medicine in Plasma Cell Myeloma
Philip Egan, Stephen Drain, Caroline Conway, Anthony Bjourson, H. Alexander
International Journal of Molecular Sciences.2016; 17(10): 1760. CrossRef
Human Myeloma Cell Lines Induce Osteoblast Downregulation of CD99 Which Is Involved in Osteoblast Formation and Activity
Angela Oranger, Giacomina Brunetti, Claudia Carbone, Graziana Colaianni, Teresa Mongelli, Isabella Gigante, Roberto Tamma, Giorgio Mori, Adriana Di Benedetto, Marika Sciandra, Selena Ventura, Katia Scotlandi, Silvia Colucci, Maria Grano
Journal of Immunology Research.2015; 2015: 1. CrossRef
CD99 regulates CXCL12-induced chemotaxis of human plasma cells
Minchan Gil, Hyo-Kyung Pak, A-Neum Lee, Seo-Jung Park, Yoonkyung Lee, Jin Roh, Hyunji Lee, Yoo-Sam Chung, Chan-Sik Park
Immunology Letters.2015; 168(2): 329. CrossRef

Prognostic Significance of Absolute Lymphocyte Count/Absolute Monocyte Count Ratio at Diagnosis in Patients with Multiple Myeloma: Su-Jin Shin, Jin Roh, Misung Kim, Min Jung Jung, Young Wha Koh, Chan-Sik Park, Dok Hyun Yoon, Cheolwon Suh, Chan-Jeong Park, Hyun Sook Chi, Jooryung Huh; Korean J Pathol. 2013;47(6):526-533. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.526

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Abstract PDF

Background

Absolute lymphocyte count (ALC) in peripheral blood has recently been reported to be an independent prognostic factor in multiple myeloma (MM). Previous studies indicated that the absolute monocyte count (AMC) in peripheral blood reflects the state of the tumor microenvironment in lymphomas. Neither the utility of the AMC nor its relationship with ALC has been studied in MM.

Methods

The prognostic value of ALC, AMC, and the ALC/AMC ratio at the time of diagnosis was retrospectively examined in 189 patients with MM.

Results

On univariate analysis, low ALC (<1,400 cells/µL), high AMC (≥490 cells/µL), and low ALC/AMC ratio (<2.9) were correlated with worse overall survival (OS) (p=.002, p=.038, and p=.001, respectively). On multivariate analysis, the ALC/AMC ratio was an independent prognostic factor (p=.047), whereas ALC and AMC were no longer statistical significant. Low ALC, high AMC, and low ALC/AMC ratio were associated with poor prognostic factors such as high International Staging System stage, plasmablastic morphology, hypoalbuminemia, and high β2-microglobulin.

Conclusions

Univariate analysis demonstrated that changes in ALC, AMC, and the ALC/AMC ratio are associated with patient survival in MM. Multivariate analysis showed that, of these factors, the ALC/AMC ratio was an independent prognostic factor for OS.

Citations

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Xiaoming Wang, Dayu Chen, Yuyan Ma, Dongping Mo, Feng Yan
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Descriptive analysis and prognostic factors in cats with myeloma‐related disorders: A multicenter retrospective study of 50 cases
Lorris Lecot, Isabelle Desmas‐Bazelle, Sarah Benjamin, Pauline De Fornel, Frédérique Ponce, Matthew Kornya, Loïc Desquilbet, Claire Beaudu‐Lange, Catherine Ibisch, David Sayag, Ghita Benchekroun, Jérémy Béguin
Journal of Veterinary Internal Medicine.2024;[Epub] CrossRef
Definers and drivers of functional high-risk multiple myeloma: insights from genomic, transcriptomic, and immune profiling
Rahul Banerjee, Kara I. Cicero, Sarah S. Lee, Andrew J. Cowan
Frontiers in Oncology.2023;[Epub] CrossRef
Normal Absolute Monocyte Count in Combination with Normal/High Absolute Lymphocyte Count at the Time of Relapse is Associated with Improved Survival in Patients with Early Relapsed Acute Myeloid Leukemia
Yu Zhang, Kanchun Dai, Qianying Zhang, Yisha Huang, Yiyun Feng, Deeksha Bhardwaj, Kang Yu, Jianhua Feng
Cancer Investigation.2021; 39(6-7): 550. CrossRef
Real World Experience of Daratumumab: Evaluating Lymphopenia and Adverse Events in Multiple Myeloma Patients
Francesca Cottini, Ying Huang, Nita Williams, Naresh Bumma, Abdullah M. Khan, Maria Chaudhry, Srinivas Devarakonda, Yvonne A. Efebera, Don M. Benson, Ashley E. Rosko
Frontiers in Oncology.2021;[Epub] CrossRef
Are the Derived Indexes of Peripheral Whole Blood Cell Counts (NLR, PLR, LMR/MLR) Clinically Significant Prognostic Biomarkers in Multiple Myeloma? A Systematic Review And Meta-Analysis
Xinwen Zhang, Jialin Duan, Zhenyu Wen, Hao Xiong, Xiaomin Chen, Yang Liu, Kunyu Liao, Chunlan Huang
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Karen Sweiss, Jonathan Lee, Nadim Mahmud, Gregory S. Calip, Youngmin Park, Dolores Mahmud, Damiano Rondelli, Pritesh R. Patel
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Low absolute CD4+ T cell counts in peripheral blood predict poor prognosis in patients with newly diagnosed multiple myeloma
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Leukemia & Lymphoma.2020; 61(8): 1869. CrossRef
Normal Absolute Monocyte Count at the Time of Relapse is Associated with Improved Survival After First Salvage Therapy in Adult Patients with Early Relapsed B-Lineage Acute Lymphoblastic Leukemia

Yi-fen Shi, Na Wang, Zi-yang Huang, Rong-rong Chen, Yi-sha Huang, Yi-yi Zhu, Chong-yun Xing, Bin Liang, Kang Yu, Jian-hua Feng
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Moritz Binder, S. Vincent Rajkumar, Martha Q. Lacy, Morie A. Gertz, Francis K. Buadi, Angela Dispenzieri, Yi L. Hwa, Amie Fonder, Miriam Hobbs, Suzanne R. Hayman, Steven R. Zeldenrust, John A. Lust, Stephen J. Russell, Nelson Leung, Prashant Kapoor, Ronal
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Effect of absolute monocyte count post-transplant on the outcome of patients with acute myeloid leukemia undergoing myeloablative allogeneic hematopoietic stem cell transplant with busulfan and cyclophosphamide conditioning
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Qian Li, Shuang Gao, Jing Ma, Su Liu, Yuanfang Yue, Lin Chen, Han Li, Xue Wang, Dongying Li, Zeng Cao, Zhigang Zhao, Xiaofang Wang, Yong Yu, Yizhuo Zhang, Yafei Wang
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The lymphocyte to monocyte ratio in peripheral blood represents a novel prognostic marker in patients with pancreatic cancer
Michael Stotz, Joanna Szkandera, Tatjana Stojakovic, Julia Seidel, Hellmut Samonigg, Peter Kornprat, Renate Schaberl-Moser, Fridericke Seggewies, Gerald Hoefler, Armin Gerger, Martin Pichler
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Case Report

Cytologic Diagnosis of Malignant Pleural Effusion in Multiple Myeloma: Two Case Reports.: Yoo Duk Choi, Sung Sun Kim, Chang Woo Han, Ji Shin Lee, Jong Hee Nam, Sang Woo Juhng, Chan Choi; Korean J Pathol. 2009;43(4):382-385.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.382

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Abstract PDF

Malignant pleural effusion in multiple myeloma (MM) is extremely rare and is associated with poor prognosis. We experienced two cases of MM IgA type with malignant pleural effusion. The diagnoses were based on characteristic cytology and CD138 immunocytochemistry. The patients received several cycles of combination chemotherapy, since symptoms were more aggressive with an uncontrolled pleural effusion. We review the clinical features of these cases and literature concerning myelomatous pleural effusion.

Citations

Citations to this article as recorded by

Características de los pacientes con derrame pleural mielomatoso. Revisión sistemática
V. Riveiro, L. Ferreiro, M.E. Toubes, A. Lama, J.M. Álvarez-Dobaño, L. Valdés
Revista Clínica Española.2018; 218(2): 89. CrossRef
Characteristics of patients with myelomatous pleural effusion. A systematic review
V. Riveiro, L. Ferreiro, M.E. Toubes, A. Lama, J.M. Álvarez-Dobaño, L. Valdés
Revista Clínica Española (English Edition).2018; 218(2): 89. CrossRef
A 76-Year-Old Man With Anemia, Bone Pain, and Progressive Dyspnea
Thitiporn Suwatanapongched, Prapaporn Pornsuriyasak, Wasana Kanoksil, Thotsaporn Morasert, Warapat Virayavanich
Chest.2014; 145(4): 913. CrossRef

Original Articles

bcl-2 and p53 Protein Expression in Multiple Myeloma and Non-tumorous Plasma Cells A study related to survival.: Yu Na Kang, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Young Jae Lee; Korean J Pathol. 1999;33(3):179-186.

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Abstract PDF: The gene product of bcl-2 (B-cell leukemia/lymphoma-2) was suggested to suppress programmed cell death (apoptosis) of tumor cells and be involved in the development of multiple myeloma. However, the normal plasma cells also express the protein. It is unclear whether the expression of bcl-2 in multiple myeloma is of normal character or of regulatory adaptation in association with neoplastic transformation. p53 was also suggested to be involved in tumor progression since mutations on p53 were found in multiple myeloma. In order to find the relationship between the expression patterns of bcl-2 and p53 in tumor cells of multiple myeloma and non-neoplastic plasma cells, we examined 38 cases of multiple myeloma and 10 cases of nasal polyp immunohistochemically. Furthermore, expression of bcl-2 and p53, mitosis, clinical stage and infiltrative pattern of tumor cells in bone marrow were also evaluated in association with the survival of patients. By immunostaining with anti-bcl-2 and p53 monoclonal antibody, 37 out of 38 cases of multiple myeloma and all of 10 cases of nasal polyp were positive for bcl-2 but only 7 cases of multiple myeloma were positive for p53. Marked dysplasia, low percentage of bcl-2 expression, and increased mitoses were correlated with poor prognosis. Based on these observations, we suggest that bcl-2 and p53 are involved in tumorigenesis of multiple myeloma and the survival of patients would be influenced by dysplastic change, mitosis and degree of bcl-2 expression.

The Increased Expression and Diagnostic Usefulness of CD56 Antigen in Paraffin Embedded Plasma Cell Neoplasm.: Seok Hyung Kim, Chan Sik Park, Eun Young Choi, Hyun Wook Kang, Seong Hoe Park, Doo Hyun Chung; Korean J Pathol. 2001;35(3):201-205.

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Abstract PDF: BACKGROUND
The natural killer cell antigen CD56 (NCAM) is a member of the immunoglobulin superfamily and is expressed on neurons, astrocytes, and Schwann cells. Recently, it has been reported that CD56 expression is detected on plasma cells of multiple myeloma by flow cytometry.
METHOD
In this study, to test the diagnostic usefulness of the anti-CD56 antibody for plasma cell neoplasm on paraffin-embedded materials, we performed immunohistochemical staining of samples from 19 patients with plasma cell neoplasms. These cases included 14 cases of multiple myeloma, 3 cases of solitary plasmacytoma of the bone, and two cases of extramedullary plasmacytoma.
RESULTS
The neoplastic plasma cells from 68 % of the patients with plasma cell neoplasms expressed CD56 highly. CD56 was expressed in all three cases of solitary plasmacytoma of the bone and one of two extramedullary plasmacytoma, and nine out of 14 multiple myeloma cases. In contrast, reactive plasma cells from the 18 patients with miscellaneous lesions were completely negative for CD56.
CONCLUSIONS
CD56 is aberrantly expressed on the neoplastic plasma cells, and it may be used as a useful marker for the diagnosis of plasma cell neoplasms in paraffin-embedded tissues.

Questionable Role of Human Herpesvirus-8 in the Pathogenesis of Multiple Myeloma.: Min Sun Cho, Shi Nae Lee; Korean J Pathol. 2005;39(3):164-167.

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Abstract PDF: BACKGROUND
Human herpesvirus 8 (HHV-8) has been strongly implicated in the etiopathogenesis of multiple myeloma. Cytokines, especially interleukin-6, that are produced by HHV-8 infected bone marrow stromal cells may play a role in the proliferation of neoplastic plasma cells. Viral DNA sequences have been detected in the bone marrow and peripheral blood cells of myeloma patients. Yet some investigators have not found the same results.
METHODS
We exmined the presence of HHV-8 DNA in the paraffin-embedded cell block specimens of bone marrow aspirations from 26 patients with multiple myeloma by polymerase chain reaction (PCR) with KS330(233) primers. Thirteen cases of bone marrow aspirations from patients with other diseases were used as a negative control. The DNA extracted from the BC-1 cell line was used as a positive control. Immunohistochemistry using commercially available HHV-8 antibody was done in the cases that were proven HHV-8 DNA-positive by PCR.
RESULTS
One case (3.9%) among the 26 patients with myleoma was positive for HHV-8 DNA by PCR, but no positive cells were detected in this case by immunohistochemistry.
CONCLUSIONS
We could not find a clear relation between myeloma and HHV-8 in Korean patients examined in the present study.

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