title: The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas.
abstract: Prognostic significance of immune microenvironment has been emphasized using the most advanced analysis, with consecutive attempts to reveal prognostic impact of this findings. The aim of this study was to compare and define prognostic significance of clinical parameters, microvessel density (MVD) in tumour tissue and expression of CD44s as adhesive molecule on tumour cells in diffuse large B cell lymphoma-DLBCL, primary central nervous system DLBCL-CNS DLBCL and follicular lymphoma-FL. A total of 202 histopathological samples (115 DLBCL/65 FL/22 CNS DLBCL) were evaluated. Overall response (complete/partial remission) was achieved in 81.3 % DLBCL patients, 81.8 % primary CNS DLBCL and 92.3 % FL. Absolute lymphocyte count-ALC/Absolute monocyte count-AMC >2.6 in DLBCL and ALC/AMC ≥ 4.7 in FL were associated with better event-free survival (EFS) and overall survival (OS) (p < 0.05). In DLBCL, MVD > 42 blood vessels/0.36 mm(2) correlated with primary resistant disease (p < 0.0001), poorer EFS and OS (p = 0.014). High CD44s expression in FL correlated with inferior EFS and OS (p < 0.01). In DLBCL, multivariate Cox regression analysis showed that ALC/AMC was independent parameter that affected OS (HR 3.27, 95 % CI 1.51-7.09, p = 0.003) along with the NCCN-IPI (HR 1.39, 95 % CI 1.08-1.79, p = 0.01). Furthermore, in FL, ALC/AMC mostly influenced OS (HR 5.21, 95 % CI 1.17-23.21, p = 0.03), followed with the FLIPI (HR 3.98, 95 % CI 1.06-14.95, p = 0.041). In DLBCL and FL, ALC/AMC is simple and robust tool that is, with current prognostic scores, able to define long-term survival and identify patients with inferior outcome. The introduction of immunochemotherapy might altered the prognostic significance of microenvionmental biomarkers (MVD and CD44s).
authors.affiliation: Clinic of Haematology, Clinical Centre of Serbia, 2, Koste Todorovica 2 str, 11000, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Jelicic
authors.affiliation: Clinic of Haematology, Clinical Centre of Serbia, 2, Koste Todorovica 2 str, 11000, Belgrade, Serbia. bb.lena@gmail.com.|Faculty of Medicine, University of Belgrade, Belgrade, Serbia. bb.lena@gmail.com.
authors.forename: Milena Todorovic
authors.initials: MT
authors.lastname: Balint
authors.affiliation: Department of Histopathology, Clinical Centre of Serbia, Belgrade, Serbia.
authors.forename: Maja Perunicic
authors.initials: MP
authors.lastname: Jovanovic
authors.affiliation: Institute for Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Novica
authors.initials: N
authors.lastname: Boricic
authors.affiliation: Department of Histopathology, Clinical Centre of Serbia, Belgrade, Serbia.
authors.forename: Marjan
authors.initials: M
authors.lastname: Micev
authors.affiliation: Department of Histopathology, Clinical Centre of Serbia, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Stojsic
authors.affiliation: Clinic of Haematology, Clinical Centre of Serbia, 2, Koste Todorovica 2 str, 11000, Belgrade, Serbia.|Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Darko
authors.initials: D
authors.lastname: Antic
authors.affiliation: Clinic of Haematology, Clinical Centre of Serbia, 2, Koste Todorovica 2 str, 11000, Belgrade, Serbia.|Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Bosko
authors.initials: B
authors.lastname: Andjelic
authors.affiliation: Clinic of Haematology, Clinical Centre of Serbia, 2, Koste Todorovica 2 str, 11000, Belgrade, Serbia.|Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Bila
authors.affiliation: Institute for Transfusiology and Hemobiology, MMA, Belgrade, Serbia.
authors.forename: Bela
authors.initials: B
authors.lastname: Balint
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Pavlovic
authors.affiliation: Clinic of Haematology, Clinical Centre of Serbia, 2, Koste Todorovica 2 str, 11000, Belgrade, Serbia.|Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Mihaljevic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D018655:Lymphocyte Count / Q000379:methods; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D059016:Tumor Microenvironment / Q000502:physiology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors
keywords: Adhesion; Angiogenesis; Lymphocyte-to-monocyte count; Lymphoma