Journal of Pathology and Translational Medicine

Original Articles

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; J Pathol Transl Med. 2016;50(5):361-368. Published online August 7, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.19

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Background
CD99 is a cell surface transmembrane glycoprotein expressed in various tissues. CD99 is differentially expressed between subpopulations of each tissue and is highly expressed in certain hematopoietic and precursor cells. However, there has been no comprehensive study of CD99 expression in normal skin. We evaluated CD99 expression in normal human skin and developing fetal skin.
Methods
Seventy-five adult skin samples containing normal skin and eight fetal skin samples of different gestational ages were collected. CD99 immunohistochemical staining was performed to evaluate expression pattern in adult and fetal skin samples. CD99 and CD34 expression were compared by double immunofluorescence.
Results
In normal adult skin, CD99 was strongly expressed in the membrane of epidermal basal keratinocytes, hair follicle bulges and outer root sheaths, and inner secretory cells of eccrine sweat glands. In fetal skin, CD99 was not expressed on the periderm at 16 weeks of gestation but was expressed in basal cells of fetal skin at around 19 weeks of gestation. CD99 expression became comparable to that of the adult skin after 20 weeks of gestation. CD99 and CD34 were co-expressed in hair follicle outer root sheaths, as seen by double immunofluorescence study.
Conclusions
This is the first study examining CD99 expression pattern in normal adult and fetal skin. CD99 tends to be expressed in the basal/precursor cells of epidermis and in hair follicles. These results provide a basis for future investigation on functions of CD99 in the skin and provide a novel potential target for the treatment of dermatologic lesions.

Citations

Citations to this article as recorded by

Childhood pilomatrixoma mimicking malignant small round blue cell tumor with positivity for CD99: Potential pitfall in cytology
Brijdeep Singh, Radhika Srinivasan, Deepak Bansal, Manish Rohilla, Pranab Dey, Uma Nahar Saikia, Ritambhra Nada
Diagnostic Cytopathology.2023;[Epub] CrossRef
Role of CD99 in regulating homeostasis and differentiation in normal human epidermal keratinocytes
Yi Li Wong, Toru Okubo, Eiko Uno, Kazuma Suda, Tsuyoshi Ishii
Biochemical and Biophysical Research Communications.2022; 606: 108. CrossRef
Anti-human CD99 antibody exerts potent antitumor effects in mantle cell lymphoma
Nuchjira Takheaw, Gunya Sittithumcharee, Ryusho Kariya, Watchara Kasinrerk, Seiji Okada
Cancer Immunology, Immunotherapy.2021; 70(6): 1557. CrossRef
“Neuroectodermal influence of CD 99 immunoexpression correlates with the clinical behavior of odontogenic cysts and tumors”
Harshi Mishra, Nikita Gulati, Anshi Jain, Saurabh Juneja, DeviCharan Shetty
Journal of Oral and Maxillofacial Pathology.2021; 25(3): 423. CrossRef
CD99 at the crossroads of physiology and pathology
Michela Pasello, Maria Cristina Manara, Katia Scotlandi
Journal of Cell Communication and Signaling.2018; 12(1): 55. CrossRef
CD99: A Cell Surface Protein with an Oncojanus Role in Tumors
Maria Manara, Michela Pasello, Katia Scotlandi
Genes.2018; 9(3): 159. CrossRef

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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Abstract PDF

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

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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

Case Reports

Multiple Jejunal Myeloid Sarcomas Presenting with Intestinal Obstruction in a Non-leukemic Patient: A Case Report with Ultrastructural Observations: Na Rae Kim, Woon Kee Lee, Jong In Lee, Hyun Yee Cho; Korean J Pathol. 2012;46(6):590-594. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.590

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Abstract PDF

Myeloid sarcoma is a rare extramedullary myeloid tumor, which is frequently misdiagnosed when no evidence of leukemia is initially observed. Here, we report on a peculiar case of a 49-year-old man afflicted with multiple masses in the jejunum, the superior mesentery, and the serosa of the transverse colon, without leukemic manifestation. The tumor was composed of undifferentiated small round cells containing eosinophilic cytoplasm, which were negative for myeloperoxidase, nonspecific esterase, lysozyme, terminal deoxynucleotidyl transferase, leukocyte common antigen, CD3, CD4, CD15, CD20, CD30, CD43, CD56, CD68/PG-M1, CD79a, human melanoma black-45, c-kit, and CD34 with positivity only for CD68/KP1, CD99, and vimentin. Under electron microscopy, those cells had abundant membrane-bound cytoplasmic granules that measured 200 to 300 nm in diameter, which were consistent with granulocytic azurophilic granules. The tumor was finally diagnosed as a myeloid sarcoma. The presence of non-leukemic myeloid sarcomas showing immunonegativity for conventional myeloid-leukemic markers necessitated a diagnosis by ultrastructural observation.

Citations

Citations to this article as recorded by

Isolated myeloid sarcoma presenting with small bowel obstruction: a case report
Rie Mizumoto, Masanori Tsujie, Tomoko Wakasa, Kotaro Kitani, Hironobu Manabe, Shuichi Fukuda, Kaoru Okada, Shumpei Satoi, Hajime Ishikawa, Toshihiko Kawasaki, Hitoshi Hanamoto, Masao Yukawa, Masatoshi Inoue
Surgical Case Reports.2020;[Epub] CrossRef
Primary Myeloid Sarcoma of the Ileum and Mesentery Causing Small Bowel Obstruction: Case Report and Literature Review
Andrej Nikolovski, Dragoslav Mladenovikj, Aleksandra Veljanovska, Gordana Petrusevka
Lietuvos chirurgija.2020; 19(1-2): 55. CrossRef
Utility of Transmission Electron Microscopy in Small Round Cell Tumors
Na Rae Kim, Seung Yeon Ha, Hyun Yee Cho
Journal of Pathology and Translational Medicine.2015; 49(2): 93. CrossRef

Solitary Fibrous Tumor of the Conjunctiva with Heretofore Undescribed Pathologic Findings.: Na Rae Kim, Jae Y Ro, Kyung Hwan Shin, Hae Jung Paik, Jung Suk An, Seung Yeon Ha; Korean J Pathol. 2011;45(3):315-318.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.315

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1 Crossref

Abstract PDF

A 37-year-old female presented with a conjunctival mass discovered 3 years prior. An excisional biopsy revealed a patternless proliferation of round and spindle-shaped cells with an eosinophilic fibrillary cytoplasm and vesicular nuclei with occasional inclusions. Psammoma bodies were arranged around the dilated irregularly-shaped vessels. Differential diagnoses included conjunctival solitary fibrous tumor (SFT), nevus, glomangioma, ectopic meningioma, and mesectodermal leiomyoma. The tumor cells were immunoreactive for CD34, CD99, bcl-2 and vimentin, and were negative for smooth muscle actin, desmin, glial fibrillary acidic protein, S-100 protein, epithelial membrane antigen, and human melanoma black-45. Ultrastructurally, the tumor cells had rough endoplasmic reticulum, free ribosomes, and scattered mitochondria without basal lamina or cellular junctions, which are features of fibroblasts. A diagnosis of SFT was rendered based on the light microscopic, immunohistochemical, and electron microscopic findings. We report here on the second case of a SFT arising in the conjunctiva, which clinically and histologically mimics conjunctival nevus, glomangioma, ectopic meningioma, and a hybrid neurogenic-myogenic tumor such as mesectodermal leiomyoma.

Citations

Citations to this article as recorded by

Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis
Nayoung Han, Hannah Kim, Soo Kee Min, Sun-Ha Paek, Chul-Kee Park, Seung-Hong Choi, U-Ri Chae, Sung-Hye Park
Journal of Pathology and Translational Medicine.2016; 50(2): 113. CrossRef

Original Article

Significance of CD99 Immunoreactive Cells in relation to Gastrin-producing Cells in Human Gastric Mucosa.: Eun Young Kim, Jong Im Lee, Jung Ran Kim; Korean J Pathol. 2003;37(4):263-269.

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Abstract PDF: BACKGROUND
CD99 is characteristically expressed in Ewing's sarcoma/primitive neuroendocrine tumors and its immunoreactivity has also been reported in gastrointestinal neuroendocrine tumors. However, the normal distribution of CD99 reactive cells in gastrointestinal mucosa and their function are not fully understood.
METHODS
We performed an immunohistochemical study using antibodies to CD99 and gastrin on formalin fixed and paraffin embedded tissue of the stomach.
RESULTS
CD99 were strongly expressed in the gastric glands of neonate (3/3) and infant (1/1) cases but not detected in the fetal period (0/30). In adults, CD99 was observed in 36.8% (7/19). The number of CD99 positive cells were fewer in adult (3.48+/-6.43) than in neonate (5.66+/-0.58) and infant (11.33+/-2.21). CD99 was mostly located along the cytoplasmic membrane of glandular cells but cytoplasmic expression was also evident in neonate and infant cases. The G cells and CD99 expressed cells were reduced in the area showing intestinal metaplasia and atrophic change. As a result of the double stain, some of the G cells coexpress CD99 antigen, which were more in neonate (29%) than in adult (2.6%).
CONCLUSIONS
The CD99 positive cells were found in the gastric pyloric antrum during the postnatal period and progressively reduced with age. This suggests the participation of CD99 protein in the differentiation and secretory process of neuroendocrine cells.

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