Expression and diagnostic utility of single and combined CD200, CD148 and CD160 markers in mature B‑cell neoplasms as revealed by ROC and SVM analyses

Elsaid,Ahmed F.; Omran,Alaa A.; Abd Elrhman,Heba E.

doi:10.3892/wasj.2019.16

Expression and diagnostic utility of single and combined CD200, CD148 and CD160 markers in mature B‑cell neoplasms as revealed by ROC and SVM analyses

Authors:
- Ahmed F. Elsaid
- Alaa A. Omran
- Heba E. Abd Elrhman
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Affiliations: Department of Public Health and Community Medicine, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt, Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt
Published online on: June 14, 2019 https://doi.org/10.3892/wasj.2019.16
Pages: 136-144

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Abstract

Timely and accurate diagnosis of mature B‑cell neoplasm (MBN) subtypes is crucial for initiating a proper management plan. The aim of this study was to evaluate the diagnostic utility of CD200, CD148 and CD160 in different MBN subtypes using two discriminatory statistical techniques, namely receiver operating characteristic (ROC) curve analysis and support vector machine (SVM). This study included 86 patients with MBNs, 61 males and 25 females, whose data of medical histories and clinical examinations were collected. Fresh blood/bone marrow specimens were also collected and subjected to detailed morphological, cytogenetic and flow cytometric immunophenotypic examination. Diagnosis was established according to the 2017 WHO guidelines. The discriminatory performance of single and combined markers was assessed using ROC analysis. The discriminatory accuracy of the best markers was analyzed using SVM and compared to ROC analysis. The results revealed that CD148/CD200 demonstrated the best diagnostic utility in discriminating mantle cell lymphoma (MCL) from chronic lymphocytic leukemia (CLL), and hairy cell leukemia (HCL) from lymphoplasmacytic lymphoma (LPL) plus splenic marginal zone lymphoma (SMZL), with a sensitivity and specificity of 100% at signal ratios of >2.6 and <0.15, respectively. CD200 demonstrated equivalent diagnostic performance only in discriminating HCL from LPL plus SMZL at a signal cut‑off value of >279. Discrimination between SMZL and LPL was unfeasible with any of the used markers. The discriminatory accuracy of SVM using CD148 and CD200 was comparable to that of ROC analysis. On the whole, the findings of this study indicate that CD148/CD200 demonstrated the best diagnostic utility in discriminating MCL from CLL, and HCL from LPL plus SMZL. Combined markers offer a diagnostic value, particularly in difficult cases with anomalous marker expression. SVM could be used for the efficient analysis of flow cytometric data.

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1	Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J and Vardiman JW (eds): Introduction and overview of the classification of the lymphoid neoplasms. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. IARC, Lyon. pp190–198. 2017.
2	Craig FE: Flow cytometric evaluation of B-cell lymphoid neoplasms. Clin Lab Med. 27:487–512, vi. 2007.PubMed/NCBI View Article : Google Scholar
3	Craig FE and Foon KA: Flow cytometric immunophenotyping for hematologic neoplasms. Blood. 111:3941–3967. 2008.PubMed/NCBI View Article : Google Scholar
4	Stetler-Stevenson M: Flow cytometry in lymphoma diagnosis and prognosis: Useful? Best Pract Res Clin Haematol. 16:583–597. 2003.PubMed/NCBI View Article : Google Scholar
5	Matutes E, Owusu-Ankomah K, Morilla R, Garcia Marco J, Houlihan A, Que TH and Catovsky D: The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia. 8:1640–1645. 1994.PubMed/NCBI
6	Kroft SH: Uncovering clinically relevant phenotypic variations in malignancies: CD23 in mantle cell lymphoma. Am J Clin Pathol. 130:159–161. 2008.PubMed/NCBI View Article : Google Scholar
7	Sánchez ML, Almeida J, Vidriales B, López-Berges MC, García-Marcos MA, Moro MJ, Corrales A, Calmuntia MJ, San Miguel JF and Orfao A: Incidence of phenotypic aberrations in a series of 467 patients with B chronic lymphoproliferative disorders: Basis for the design of specific four-color staining to be used for minimal residual disease investigation. Leukemia. 16:1460–1469. 2002.PubMed/NCBI View Article : Google Scholar
8	Baseggio L, Traverse-Glehen A, Petinataud F, Callet-Bauchu E, Berger F, Ffrench M, Couris CM, Thieblemont C, Morel D, Coiffier B, et al: CD5 expression identifies a subset of splenic marginal zone lymphomas with higher lymphocytosis: A clinico-pathological, cytogenetic and molecular study of 24 cases. Haematologica. 95:604–612. 2010.PubMed/NCBI View Article : Google Scholar
9	Asplund SL, McKenna RW, Doolittle JE and Kroft SH: CD5-positive B-cell neoplasms of indeterminate immunophenotype: A clinicopathologic analysis of 26 cases. Appl Immunohistochem Mol Morphol. 13:311–317. 2005.PubMed/NCBI View Article : Google Scholar
10	Dronca RS, Jevremovic D, Hanson CA, Rabe KG, Shanafelt TD, Morice WG, Call TG, Kay NE, Collins CS, Schwager SM, et al: CD5- positive chronic B-cell lymphoproliferative disorders: Diagnosis and prognosis of a heterogeneous disease entity. Cytometry B Clin Cytom. 78 (Suppl 1):S35–S41. 2010.PubMed/NCBI View Article : Google Scholar
11	Del Giudice I, Matutes E, Morilla R, Morilla A, Owusu-Ankomah K, Rafiq F, A'Hern R, Delgado J, Bazerbashi MB and Catovsky D: The diagnostic value of CD123 in B-cell disorders with hairy or villous lymphocytes. Haematologica. 89:303–308. 2004.PubMed/NCBI
12	Stetler-Stevenson M and Tembhare PR: Diagnosis of hairy cell leukemia by flow cytometry. Leuk Lymphoma. 52 (Suppl 2):S11–S13. 2011.PubMed/NCBI View Article : Google Scholar
13	Brunetti L, Di Noto R, Abate G, Gorrese M, Gravetti A, Raia M, Scalia G, Pascariello C, Camera A and Del Vecchio L: CD 200/OX2, a cell surface molecule with immune-regulatory function, is consistently expressed on hairy cell leukemia neoplastic cells. Br J Haematol. 145:665–678. 2009.PubMed/NCBI View Article : Google Scholar
14	Tonks A, Hills R, Whitw P, Roise B, Mils KI, Birnett AK and Darley RL: CD200 as a prognostic factor in acute myeloid leukemia. Leukemia. 21:566–568. 2007.PubMed/NCBI View Article : Google Scholar
15	Moreaux J, Hose D, Reme T, Jourdan E, Hyndemer M, Legouffe E, Moine P, Bourin P, Moos M, Corre J, et al: CD 200 is a new prognostic factor in multiple myeloma. Blood. 108:4194–4197. 2006.PubMed/NCBI View Article : Google Scholar
16	Sandes AF, de Lourdes Chauffaille M, Oliveria CR, Maekawa Y, Tamashro N, Takao TT, Ritter EC and Rizzatti EG: CD 200 has an important role in the differential diagnosis of mature B-cell neoplasms by multiparameter flow cytometry. Cytometry B Clin Cytom. 86:98–105. 2014.PubMed/NCBI View Article : Google Scholar
17	Pillai V, Pozdnyakova O, Charest K, Li B, Shahsafaei A and Dorfman DM: CD200 flow cytometric assessment and semiquantitative immunohistochemical staining distinguishes hairy cell leukemia from hairy cell leukemia-variant and other B-cell lymphoproliferative disorders. Am J Clin Pathol. 140:536–543. 2013.PubMed/NCBI View Article : Google Scholar
18	Miguet L, Béchade G, Fornecker L, Zink E, Felden C, Gervais C, Herbrecht R, Van Dorsselaer A, Mauvieux L and Sanglier-Cianferani S: Proteomic analysis of malignant B-cell derived microparticles reveals CD148 as a potentially useful antigenic biomarker for mantle cell lymphoma diagnosis. J Proteome Res. 8:3346–3354. 2009.PubMed/NCBI View Article : Google Scholar
19	Liu FT, Giustiniani J, Farren T, Jia L, Bensussan A, Gribben JG and Agrawal SG: CD160 signaling mediates PI3K-dependent survival and growth signals in chronic lymphocytic leukemia. Blood. 115:3079–3088. 2010.PubMed/NCBI View Article : Google Scholar
20	Shultz EK: Multivariate receiver-operating characteristic curve analysis: Prostate cancer screening as an example. Clin Chem. 41:1248–1255. 1995.PubMed/NCBI
21	Sommer C and Girlish DW: Machine learning in cell biology-teaching computers to recognize phenotypes. J Cell Sci. 126:5529–5539. 2013.PubMed/NCBI View Article : Google Scholar
22	Nayak J, Naik B and Behera HS: A comprehensive survey on support vector machine in data mining tasks: Applications & challenges. Int J Database Theory Appl. 8:169–186. 2015. View Article : Google Scholar
23	Jones CM and Athanasiou T: Summary receiver operating characteristic curve analysis techniques in the evaluation of diagnostic tests. Ann Thorac Surg. 79:16–20. 2005.PubMed/NCBI View Article : Google Scholar
24	Fan J, Upadhye S and Worster A: Understanding receiver operating characteristic (ROC) curves. CJEM. 8:19–20. 2006.PubMed/NCBI
25	DeLong ER, DeLong DM and Clarke-Pearson DL: Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach. Biometrics. 44:837–845. 1988.PubMed/NCBI
26	Chang CC and Lin CJ: LIBSVM: A Library for Support Vector Machines. ACM Transactions on Intelligent Systems and Technology. 2(27): 1–27, 27. 2011. View Article : Google Scholar : http://www.csie.ntu.edu.tw/~cjlin/libsvm.
27	Palumbo GA, Parrinello N, Fargione G, Csrdillo K, Chiarenza A, Berretta S, Conticello C, Villari L and Di Raimondo F: CD200 expression may help in differential diagnosis between mantle cell lymphoma and B-cell chronic lymphocytic leukemia. Leuk Res. 33:1212–1216. 2009.PubMed/NCBI View Article : Google Scholar
28	Challagundla P, Medeiros LJ, Kanagal-Shamanna R, Miranda RN and Jorgensen JL: Differential expression of CD 200 in B-cell neoplasms by flow cytometry can assist in diagnosis, sub classification and bone marrow staging. Am J Clin Pathol. 142:837–844. 2014.PubMed/NCBI View Article : Google Scholar
29	Fan L, Miao Y, Wu YJ, Wang Y, Guo R, Wang L, Shen AL, Chen YY, Xu W and Li JY: Expression patterns of CD200 and CD148 in leukemic B-cell chronic lymphoproliferative disorders and their potential value in differential diagnosis. Leuk Lymphoma. 56:3329–3335. 2015.PubMed/NCBI View Article : Google Scholar
30	Lesesve JF, Tardy S, Frotscher B, Latger-Cannard V, Feugier P and De Carvalho Bittencourt M: Combination of CD160 and CD200 as a useful tool for differential diagnosis between chronic lymphocytic leukemia and other mature B-cell neoplasms. Int J Lab Hematol. 37:486–494. 2015.PubMed/NCBI View Article : Google Scholar
31	Farren TW, Giustiniani J, Liu FT, Tsitsikas DA, Macey MG, Cavenagh JD, Oakervee HE, Taussig D, Newland AC, Calaminici M, et al: Differential and tumor-specific expression of CD160 in B-cell malignancies. Blood. 118:2174–2183. 2011.PubMed/NCBI View Article : Google Scholar