Membranous CD24 expression as detected by the monoclonal antibody SWA11 is a prognostic marker in non-small cell lung cancer patients

BMC Clinical Pathology

Glen Kristiansen²  Peter Altevogt¹  Lukas Heukamp³  Johannes Stein²  Angela Fuchs²  Anne Schindler²  Michael Majores² 

[1] Department of Dermatology, Venereology and Allergology University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany;Institute of Pathology, University of Bonn, Sigmund-Freud-Str. 25, Bonn, D-53127, Germany;New Pathology, Cologne, Germany

关键词: Prognostic marker;    Immunohistochemistry;    CD24;    NSCLC;    Non-small cell lung cancer;   

Others  :  1233929
DOI  :  10.1186/s12907-015-0019-z

 received in 2015-03-27, accepted in 2015-11-04,  发布年份 2015

【 摘 要 】

Background

Lung cancer is one of the most common malignant neoplasms worldwide and has a high mortality rate. To enable individualized therapy regimens, a better understanding of the molecular tumor biology has still to be elucidated. The expression of the cell surface protein CD24 has already been claimed to be associated with shorter patient survival in non-small cell lung cancer (NSCLC), however, the prognostic value and applicability of CD24 immunostaining in paraffin embedded tissue specimens has been questioned due to the recent acknowledgement of restricted epitope specificity of the commonly used antibody SN3b.

Methods

A cohort of 137 primary NSCLC cases was immunostained with a novel CD24 antibody (clone SWA11), which specifically recognizes the CD24 protein core and the resulting expression data were compared with expression profiles based on the monoclonal antibody SN3b. Furthermore, expression data were correlated to clinico-pathological parameters. Univariate and multivariate survival analyses were conducted with Kaplan Meier estimates and Cox regression, respectively.

Results

CD24 positivity was found in 34 % resp. 21 % (SN3b) of NSCLC with a membranous and/or cytoplasmic staining pattern. Kaplan-Meier analyses revealed that membranous, but not cytoplasmic CD24 expression (clone SWA11) was associated with lympho-nodular spread and shorter overall survival times (both p < 0.05). CD24 expression established by SN3b antibodies did not reveal significant clinicopathological correlations with overall survival, neither for cytoplasmic nor membranous CD24 staining.

Conclusions

Membranous CD24 immunoreactivity, as detected with antibody clone SWA11 may serve as a prognostic factor for lymphonodular spread and poorer overall survival. Furthermore, these results corroborate the importance of a careful distinction between membranous and cytoplasmic localisation, if CD24 is to be considered as a potential prognostic biomarker.

【 授权许可】

   
2015 Majores et al.

【 图 表 】

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【 参考文献 】

• [1]Siegel R, Naishadham D, Jemal A: Cancer statistics, 2013. CA Cancer J Clin 2013, 63(1):11-30.
• [2]Lee HJ, Choe G, Jheon S, Sung SW, Lee CT, Chung JH: CD24, a novel cancer biomarker, predicting disease-free survival of non-small cell lung carcinomas: a retrospective study of prognostic factor analysis from the viewpoint of forthcoming (seventh) new TNM classification. J Thorac Oncol 2010, 5(5):649-657.
• [3]Kristiansen G, Schluns K, Yongwei Y, Denkert C, Dietel M, Petersen I: CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients. Br J Cancer 2003, 88(2):231-236.
• [4]Györffy G, Surowiak S, Budczies B, Lanczky L: Online Survival Analysis Software to Asses the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer. PLOS One 2013, 18(8(12)):e82241.
• [5]Sammar M, Aigner S, Hubbe M, Schirrmacher V, Schachner M, Vestweber D, Altevogt P: Heat-stable antigen (CD24) as ligand for mouse P-selectin. Int Immunol 1994, 6(7):1027-1036.
• [6]Aigner S, Ramos CL, Hafezi-Moghadam A, Lawrence MB, Friederichs J, Altevogt P, Ley K: CD24 mediates rolling of breast carcinoma cells on P-selectin. Faseb J 1998, 12(12):1241-1251.
• [7]Aigner S, Sthoeger ZM, Fogel M, Weber E, Zarn J, Ruppert M, Zeller Y, Vestweber D, Stahel R, Sammar M, et al.: CD24, a mucin-type glycoprotein, is a ligand for P-selectin on human tumor cells. Blood 1997, 89(9):3385-3395.
• [8]Burgos-Ojeda D, Wu R, McLean K, Chen Y, Talpaz M, Yoon E, Cho KR, Buckanovich RJ: CD24+ Ovarian Cancer Cells Are Enriched for Cancer-Initiating Cells and Dependent on JAK2 Signaling for Growth and Metastasis. Mol Cancer Ther 2015, 14(7):1717-1727.
• [9]Rostoker R, Abelson S, Genkin I, Ben-Shmuel S, Sachidanandam R, Scheinman EJ, Bitton-Worms K, Orr ZS, Caspi A, Tzukerman M, et al.: CD24+ cells fuel rapid tumor growth and display high metastatic capacity. Breast Cancer Research 2015, 17:78. BioMed Central Full Text
• [10]Sterlacci MD, Savic S, Fiegl M, Obermann E, Tzankov A: Putative Stem Cell Markers in Non-Small-Cell-Lung Cancer A Clinicopathologic Characterization. J Thorac Oncol 2014, 9:41-49.
• [11]Stuelten CH, Mertins SD, Busch JI, Gowens M, Scudiero DA, Burkett MW, Hite KM, Alley M, Hollingshead M, Shoemaker RH, et al.: Complex Display of Putative Tumor Stem Cell Markers in the NCI60 Tumor Cell Line Panel. Stem Cells 2010, 28:649-660.
• [12]Wang G, Zhang Z, Ren Y: TROP-1/Ep-CAM and CD24 are potential candidates for ovarian cancer therapy. Int J Clin Exp Pathol 2015, 8(5):4705-4714.
• [13]Song SP, Zhang SB, Liu R, Yao L, Hao YQ, Liao MM, Zhang YD, Li ZH: NDRG2 down-regulation and CD24 up-regulation promote tumor aggravation and poor survival in patients with gallbladder carcinoma. Med Oncol 2012, 29(3):1879-1885.
• [14]Kristiansen G, Machado E, Bretz N, Rupp C, Winzer KJ, Konig AK, Moldenhauer G, Marme F, Costa J, Altevogt P: Molecular and clinical dissection of CD24 antibody specificity by a comprehensive comparative analysis. Lab Invest 2010, 90(7):1102-1116.
• [15]Weber E, Lehmann HP, Beck-Sickinger AG, Wawrzynczak EJ, Waibel R, Folkers G, Stahel RA: Antibodies to the protein core of the small cell lung cancer workshop antigen cluster-w4 and to the leucocyte workshop antigen CD24 recognize the same short protein sequence leucine-alanine-proline. Clin Exp Immunol 1993, 93(2):279-285.
• [16]Kristiansen G, Denkert C, Schluns K, Dahl E, Pilarsky C, Hauptmann S: CD24 is expressed in ovarian cancer and is a new independent prognostic marker of patient survival. Am J Pathol 2002, 161(4):1215-1221.
• [17]Smith SC, Oxford G, Wu Z: The Metastasis Associated Gene CD24 Is Regulated by Ral GTPase and Is Mediator of Cell Proliferation and Survival in Human Cancer. Cancer Research 2006, 66(4):1917-1922.
• [18]Benkerrou M, Jais JP, Leblond V, Durandy A, Sutton L, Bordigoni P, Garnier JL, Le Bidois J, Le Deist F, Blanche S, et al.: Anti-B-cell monoclonal antibody treatment of severe posttransplant B-lymphoproliferative disorder: prognostic factors and long-term outcome. Blood 1998, 92(9):3137-3147.
• [19]Mierke CT, Bretz N, Altevogt P: Contractile forces contribute to increased glycosylphosphatidylinositol-anchored receptor CD24-facilitated cancer cell invasion. J Biol Chem 2011, 286(40):34858-34871.
• [20]Salnikov AV, Bretz NP, Perne C, Hazin J, Keller S, Fogel M, Herr I, Schlange T, Moldenhauer G, Altevogt P: Antibody targeting of CD24 efficiently retards growth and influences cytokine milieu in experimental carcinomas. Br J Cancer 2013, 108(7):1449-1459.
• [21]Bretz N, Salnikov A, Perne C, Keller S, Wang X, Mierke C, Fogel M, Erbe-Hofmann N, Schlange T, Moldenhauer G, et al.: CD24 controls Src/STAT3 activity in human tumors. Cell Mol Life Sci 2012, 69(22):3863-3879.
• [22]Needham LK, Schnaar RL: The HNK-1 reactive sulfoglucuronyl glycolipids are ligand for L-selectin and P-selectin. Proc Natl Acad Sci USA 1993, 90:1359.
• [23]Gasic GJ: Role of plasma, platelets, and endothelial cells in tumour metastasis. Cancer Metastasis Rev 1984, 3:99-144.
• [24]Grigani G, Pacchiarini L, Pagliarino M: The possible role of blood platelets in tumour growth and dissemination. Haematologica 1986, 71:245-255.
• [25]Honn KV, Tang DG, Crissman JD: Platelets and cancer metastasis-a causal relationship. Cancer Metastasis Rev 1992, 11:325-251.
• [26]Sleeman JP, Baumann P, Cremers N, Kroese F, Gertraud O, Chiquet-Ehrismann R, Uede T, Yabita H: CD24 Expression Causes the Aquisition of Multiple Cellular Properties Associated with Tumor Growth and Metastasis. Cancer Research 2005 2005, 65(23):10783-10793.