title: High soluble CD30, CD25, and IL-6 may identify patients with worse survival in CD30+ cutaneous lymphomas and early mycosis fungoides.
abstract: Histopathology alone cannot predict the outcome of patients with CD30+ primary cutaneous lymphoproliferative disorders (CD30CLPD) and early mycosis fungoides (MF). To test the hypothesis that serum cytokines/cytokine receptors provide prognostic information in these disorders, we measured soluble CD30 (sCD30), sCD25, and selected cytokines in cell cultures and sera of 116 patients with CD30CLPD and 96 patients with early MF followed up to 20 years. Significant positive correlation was found between sCD30 levels and sCD25, CD40L, IL-6, and IL-8, suggesting that CD30+ neoplastic cells secrete these cytokines, but not Th2 cytokines. In vitro studies confirmed that sCD30, sCD25, IL-6, and IL-8 are secreted by CD30CLPD-derived cell lines. CD30CLPD patients with above normal sCD30 and sCD25 levels had worse overall and disease-related survivals, but only sCD30 retained significance in Cox models that included advanced age. High sCD30 also identified patients with worse survival in early MF. Increased IL-6 and IL-8 levels correlated with poor disease-related survival in CD30CLPD patients. We conclude that (1) neoplastic cells of some CD30CLPD patients do not resemble Th2 cells, and that (2) high serum sCD30, sCD25, IL-6, and perhaps IL-8 levels may provide prognostic information useful for patient management.
authors.affiliation: Department of Dermatology, Boston University, Roger Williams Medical Center, Providence, Rhode Island 02908, USA. mkadin@rwmc.org
authors.forename: Marshall E
authors.initials: ME
authors.lastname: Kadin
authors.forename: Igor Y
authors.initials: IY
authors.lastname: Pavlov
authors.forename: Julio C
authors.initials: JC
authors.lastname: Delgado
authors.forename: Eric C
authors.initials: EC
authors.lastname: Vonderheid
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D053285:CD30 Ligand / Q000097:blood*; D005260:Female; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism; D008223:Lymphoma / Q000097:blood / Q000276:immunology / Q000401:mortality*; D008232:Lymphoproliferative Disorders / Q000097:blood; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000097:blood / Q000276:immunology / Q000401:mortality*; D011379:Prognosis; D012878:Skin Neoplasms / Q000097:blood / Q000276:immunology / Q000401:mortality*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D053285:CD30 Ligand; C508606:CXCL8 protein, human; C508017:IL2RA protein, human; C508600:IL6 protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D016209:Interleukin-8; C505774:TNFSF8 protein, human
references.citation: Semin Arthritis Rheum. 2007 Aug;37(1):63-7
references.pmid: 17363040
references.citation: J Clin Oncol. 1998 Apr;16(4):1532-7
references.pmid: 9552063
references.citation: Blood. 2009 Sep 24;114(13):2730-2
references.pmid: 19638620
references.citation: J Am Acad Dermatol. 1993 Jun;28(6):973-80
references.pmid: 8388410
references.citation: FASEB J. 1995 Jan;9(1):81-6
references.pmid: 7821763
references.citation: Arch Dermatol. 2004 Apr;140(4):441-7
references.pmid: 15096372
references.citation: J Proteome Res. 2011 Jan 7;10(1):113-9
references.pmid: 20886858
references.citation: Arch Dermatol. 2000 Apr;136(4):504-10
references.pmid: 10768649
references.citation: J Invest Dermatol. 2000 Dec;115(6):1034-40
references.pmid: 11121138
references.citation: Ann Hematol. 2007 Jul;86(7):509-15
references.pmid: 17340135
references.citation: J Invest Dermatol. 2010 Mar;130(3):826-40
references.pmid: 19890350
references.citation: Am J Pathol. 2000 May;156(5):1479-84
references.pmid: 10793058
references.citation: Arch Dermatol. 1996 Nov;132(11):1309-13
references.pmid: 8915308
references.citation: Nat Rev Cancer. 2010 Jan;10(1):2-3
references.pmid: 20050335
references.citation: Arch Dermatol. 1996 Jan;132(1):42-7
references.pmid: 8546482
references.citation: Blood. 2000 Jun 15;95(12):3653-61
references.pmid: 10845893
references.citation: J Am Acad Dermatol. 2009 Aug;61(2):271-5
references.pmid: 19481294
references.citation: Am J Pathol. 2001 Apr;158(4):1231-7
references.pmid: 11290540
references.citation: Cancer Treat Res. 2008;142:349-65
references.pmid: 18283794
references.citation: Hum Pathol. 2000 Dec;31(12):1482-90
references.pmid: 11150373
references.citation: J Cutan Pathol. 2006 Feb;33 Suppl 1:10-7
references.pmid: 16412208
references.citation: Arch Dermatol. 2001 Jul;137(7):949-52
references.pmid: 11453817
references.citation: Br J Dermatol. 2006 Aug;155(2):379-86
references.pmid: 16882178
references.citation: Blood. 2005 May 15;105(10):3768-85
references.pmid: 15692063
references.citation: Oncologist. 2006 Sep;11(8):955-7; author reply 957
references.pmid: 16951399
references.citation: Am J Surg Pathol. 2009 Dec;33(12):1860-8
references.pmid: 19898220
references.citation: Ann Oncol. 1992 Sep;3 Suppl 4:49-52
references.pmid: 1333270
references.citation: Clin Vaccine Immunol. 2009 Sep;16(9):1327-31
references.pmid: 19605595
references.citation: Blood. 1985 Oct;66(4):848-58
references.pmid: 3876124
references.citation: Br J Dermatol. 2003 Mar;148(3):580-6
references.pmid: 12653754
references.citation: J Clin Oncol. 1994 Apr;12(4):793-7
references.pmid: 8151321