title: Flow cytometry CD4(+)CD26(-)CD38(+) lymphocyte subset in the microenvironment of Hodgkin lymphoma-affected lymph nodes.
abstract: Hodgkin lymphoma (HL) is traditionally diagnosed by the presence of neoplastic Hodgkin and Reed-Sternberg (HRS) cells found in minority within a typical inflammatory microenvironment. It is now recognized that the majority of these T CD4 cells are T regulatory (Treg) and play an important immunosuppressive role and contribute to tumour persistence. Flow cytometric immunophenotyping of lymphocytes was performed on lymph node samples over a 12-year period (2000-2012) to identify the Hodgkin-specific subset and potential biomarkers related to Treg cells. CD3, CD19 and T CD4(+)CD26(-)CD38(+) subsets were measured in the lymphocytic infiltrate of 108 consecutive lymph node samples concurrently diagnosed histologically as HL and in 43 cases of benign reactive lymphoid hyperplasia (BRLH). HL, compared to BRLH, shows statistically significant differences within the reactive microenvironmental population: decreased CD19(+) cells (23 % vs 39 %; p < 0.001), increased CD3(+) (74 % vs 58 %; p < 0.001) and CD4(+)CD26(-)CD38(+) cells (38 % vs 11.5 %; p < 0.001). By using the co-expressed markers CD38 and CD26 for logistic analysis, the obtained receiver operating characteristic (ROC) curves confirm that the CD4(+)CD26(-)CD38(+) subset is strongly expressed in HL (ROC AUC = 0,8639). Flow cytometric detection of CD4(+)CD26(-)CD38(+) cells seems able to identify the cellular microenvironmental pattern in HL and to distinguish it from BRLH. Although there is extensive experience in flow cytometric analysis of non-HL, it is not routinely applied in cases of HL and our findings suggest that it may be useful in quickly and easily characterizing its cellular para-neoplastic inflammatory background.
authors.affiliation: Laboratory Department, Transfusion Service, Haemophilia Centre and Haematology, Castelfranco Veneto Hospital, Via Ospedale 18, 31033, Castelfranco Veneto, TV, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Di Gaetano
authors.forename: Valentina
authors.initials: V
authors.lastname: Gasparetto
authors.forename: Andrea
authors.initials: A
authors.lastname: Padoan
authors.forename: Barbara
authors.initials: B
authors.lastname: Callegari
authors.forename: Laura
authors.initials: L
authors.lastname: Candiotto
authors.forename: Maria Colomba
authors.initials: MC
authors.lastname: Sanzari
authors.forename: Antonio
authors.initials: A
authors.lastname: Scapinello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tagariello
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D019540:Area Under Curve; D001782:Blood Donors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D003937:Diagnosis, Differential; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis; D005434:Flow Cytometry; D006689:Hodgkin Disease / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000032:analysis; D019310:Pseudolymphoma / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D012372:ROC Curve; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4