Prognostički značaj angiogeneze i ekspresije adhezivnih molekula stromalnih ćelija kod bolesnika sa folikularnim i difuznim B krupnoćelijskim limfomom
The prognostic signifficance of angiogenesis and expression of adhesive molecules on stromal cells in diffuse large B cell and follicular lymphoma patients
Author
Jeličić, Jelena J.Mentor
Todorović-Balint, MilenaCommittee members
Mihaljević, BiljanaĐurđević, Predrag
Pavlović, Sonja
Metadata
Show full item recordAbstract
Značaj tumorske mikrosredine limfoma je prepoznat upotrebom
najsavremenijih tehnologija sa posledičnom analizom prognostičkog značaja ovih
rezultata. Poznavanje tumorske mikrosredine difuznog B krupnoćelijskog limfoma
(DBKL), folikularnog limfoma (FL), kao i genetske osnove primarnog DBKL centralnog
nervnog sistema (DBKL CNS) kao posebnog podentiteta u okviru DBKL je još uvek
nedovoljno.
Cilj ove studije je bio analiza prognostičkog značaja kliničkih parametara, gustine
krvnih sudova merene ekspresijom CD34 na endotelnim ćelijama u tumorskom tkivu,
ekspresije CD44s kao adhezivnog molekula na stromalnim i tumorskim ćelijama, i
ekspresije transkipcionog faktora FOXP1 na tumorskim ćelijama DBKL, primarnog
DBKL CNS-a i FL.
Metoda: Analizirana su 202 patohistološka uzorka fiksirana na formalinu i
ukalupljena na parafinu (115 DLBCL/65 FL/22 primarni DLBCL CNS). Korišćenjem
MiSeq i TruSeqAmplicon Cancer Panel-a (TSCAP) za 48 kancer-povezanih gena
analizirano je 19 bolesnika sa primarnim DBKL ...CNS-a.
Rezultati: Povoljan terapijski odgovor (kompletna/parcijalna remisija) je
postignut kod 81.3% bolesnika sa DBKL, 81.8% sa primarnim DBKL CNS i 92.3% sa
FL. Pored kliničkih parametara koji su pokazali uticaj na ukupno preživljavanje i
preživljavanje bez pojave bolesti, utvrđen je značaj visoke gustine krvnih sudova kod
bolesnika sa DBKL, a visoke ekspresije CD44s adhezivnog molekula na tumorskim
ćelijama kod FL. Multivarijanta analiza je kod DBKL pokazala prognostički značaj na
preživljavanje gustine krvnih sudova zajedno sa NCCN-IPI-jem (p=0.026, p<0.001), dok
su se kod FL izdovojili FLIPI, pol, ALC/AMC (absolutni broj limfocita/ absolutni broj
monocita u perifernoj krvi), gradus FL i visoka FOXP1 ekspresija (p=0.006, p=0.007,
p=0.016, p=0.034, p=0.014) kao prognostički značajni markeri. Bolesnici sa primarnim
DBKL CNS-a su imali bolje preživljavanje ukoliko je prethodno sprovedena kompletna
tumorska resekcija (p=0.03)...
The significance of tumor immune microenvironment has been
emphasized using the most advanced analysis, with consecutive attempts to reveal
prognostic impact of this findings. Furthermore, the knowledge about tumor
microenviroment of diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL)
as well as the genomic basis of primary central nervous system DLBCL (CNS DLBCL),
as the special entity within DLBCL, is still insufficient.
The aim of this study was to compare and define the prognostic significance of
clinical parameters, microvessel density (MVD) in tumour tissue labelled with anti CD34
antibody on endothelial cells of tumour blood vessels, expression of CD44s as adhesive
molecule on stromal and tumour cells, as well as transcription factor FOXP1 on tumor
cells of DLBCL, primary CNS DLBCL and FL.
Methods: A total of 202 formalin fixed, paraffin-embedded tumor samples (115
DLBCL/65 FL/22 primary CNS DLBCL) were evaluated. Using the MiSeq and
TruSeqAmplicon Cancer Panel (TSCA...P) for 48 cancer-related genes, 19 primary CNS
DLBCL were investigated.
Results: Overall response (complete/partial remission) was achieved in 81.3%
DLBCL patients, 81.8% primary CNS DLBCL and 92.3% FL. Beside clinical parameters
that were significant for overall survival (OS) and event free survival (EFS), high MVD
in DLBCL correlated with poorer outcome, while in FL high CD44s expression correlated
with inferior EFS and OS. In DLBCL, multivariate regression analysis showed that MVD
along with NCCN-IPI (p=0.026, p<0.001) were the most important parameters that
influenced survival, and in FL were as following: FLIPI, gender, ALC/AMC (absolute
lymphocyte count/absolute monocyte count), FL histological grade and high FOXP1
expression (p=0.006, p=0.007, p=0.016, p=0.034, p=0.014, respectively). In primary
CNS DLBCL complete tumor extirpation correlated previous to chemotherapy with
favourable outcome (p=0.03)...
Faculty:
Универзитет у Београду, Медицински факултетDate:
04-04-2016Projects:
- Rare Diseases:Molecular Pathophysiology, Diagnostic and Therapeutic Modalities and Social, Ethical and Legal Aspects (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41004)