title: Immunohistochemical analysis of IL-6, IL-8/CXCR2 axis,  Tyr p-STAT-3, and SOCS-3 in lymph nodes from patients with chronic lymphocytic leukemia: correlation between microvascular characteristics and prognostic significance.
abstract: A number of studies have looked into the pathophysiological role of angiogenesis in CLL, but the results have often been inconsistent. We aimed to gain direct insight into the angiogenic process in lymph nodes involved by CLL, focusing on proangiogenic cytokines and microvessel morphometry. The tissue levels of VEGF, Th-2 cytokines IL-6 and IL-8, IL-8 receptor CXCR2, and tyrosine p-STAT-3/SOCS-3 axis modulating cytokine expression were evaluated immunohistochemically in 62 CLL/SLL cases. Microvascular characteristics were evaluated by image analysis. Results were analyzed with regard to clinicopathological characteristics. Proliferation centers (PCs) were less well vascularised compared to non-PC areas. IL-8 and CXCR2 expression was distinctly uncommon as opposed to IL-6, VEGF and SOCS-3, which were detected in the vast majority of cases. The latter two molecule expressions were more pronounced in the PCs in ∼ 40% of the cases. p-STAT-3 immunoreactivity was recorded in 66.67% of the cases with a predilection for PCs. Microvessel morphometry was unrelated to proangiogenic cytokines, p-STAT-3, SOCS-3, or survival. Microvascular caliber and VEGF expression were higher in Binet stage A, whereas IL-6 expression was higher in stage C. VEGF and p-STAT-3 exerted a favorable effect on progression, which remained significant in multivariate analysis, thereby constituting potential outcome predictors in CLL patients.
authors.affiliation: First Department of Pathology, Laikon Hospital, University of Athens, Medical School, 75 Mikras Asias street, 11527 Athens, Greece.
authors.forename: Georgia
authors.identifier: 0000-0002-1398-178X
authors.initials: G
authors.lastname: Levidou
authors.affiliation: Athens Medical Center-Psychicon Branch, 15451 Athens, Greece.
authors.forename: Sotirios
authors.identifier: 0000-0003-4818-8033
authors.initials: S
authors.lastname: Sachanas
authors.affiliation: Athens Medical Center-Psychicon Branch, 15451 Athens, Greece.
authors.forename: Gerassimos A
authors.initials: GA
authors.lastname: Pangalis
authors.affiliation: Hematology Department, University of Crete, 70013 Heraklion, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Kalpadakis
authors.affiliation: Athens Medical Center-Psychicon Branch, 15451 Athens, Greece.
authors.forename: Xanthi
authors.initials: X
authors.lastname: Yiakoumis
authors.affiliation: Athens Medical Center-Psychicon Branch, 15451 Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Moschogiannis
authors.affiliation: First Department of Pathology, Laikon Hospital, University of Athens, Medical School, 75 Mikras Asias street, 11527 Athens, Greece.
authors.forename: Athanasia
authors.initials: A
authors.lastname: Sepsa
authors.affiliation: First Department of Pathology, Laikon Hospital, University of Athens, Medical School, 75 Mikras Asias street, 11527 Athens, Greece.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Lakiotaki
authors.affiliation: First Department of Pathology, Laikon Hospital, University of Athens, Medical School, 75 Mikras Asias street, 11527 Athens, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Milionis
authors.affiliation: Hematology Department, University of Athens, Laikon General Hospital, 11527 Athens, Greece.
authors.forename: Marie-Christine
authors.identifier: 0000-0001-9805-9112
authors.initials: MC
authors.lastname: Kyrtsonis
authors.affiliation: Hematology Department, University of Athens, Laikon General Hospital, 11527 Athens, Greece.
authors.forename: Theodoros P
authors.initials: TP
authors.lastname: Vassilakopoulos
authors.affiliation: Athens Medical Center-Psychicon Branch, 15451 Athens, Greece.
authors.forename: Pantelis
authors.initials: P
authors.lastname: Tsirkinidis
authors.affiliation: Hematology Department, University of Athens, Ipokration General Hospital, 11527 Athens, Greece.
authors.forename: Flora
authors.initials: F
authors.lastname: Kontopidou
authors.affiliation: Hematology Department, University of Athens, Attikon General Hospital, 12461 Athens, Greece.
authors.forename: Styliani
authors.initials: S
authors.lastname: Kokoris
authors.affiliation: First Department of Internal Medicine, University of Athens, Laikon General Hospital, 11527 Athens, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Siakantaris
authors.affiliation: Hematology Department, University of Athens, Laikon General Hospital, 11527 Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Angelopoulou
authors.affiliation: Hematology Department, University of Crete, 70013 Heraklion, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Papadaki
authors.affiliation: First Department of Pathology, Laikon Hospital, University of Athens, Medical School, 75 Mikras Asias street, 11527 Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kavantzas
authors.affiliation: Hematology Department, University of Athens, Laikon General Hospital, 11527 Athens, Greece.
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Panayiotidis
authors.affiliation: First Department of Pathology, Laikon Hospital, University of Athens, Medical School, 75 Mikras Asias street, 11527 Athens, Greece.
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.affiliation: First Department of Pathology, Laikon Hospital, University of Athens, Medical School, 75 Mikras Asias street, 11527 Athens, Greece.
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D011379:Prognosis; D023063:Receptors, Interleukin-8B / Q000096:biosynthesis*; D050796:STAT3 Transcription Factor / Q000096:biosynthesis*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D023063:Receptors, Interleukin-8B; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A