BCL10 aberacije i aktivacija p65 gena NF-kappa B puta su odsutne ili retke u primarnom MALT limfomu želuca

  • Jelena Hajder Clinic for Hematology and Oncology, Medical Center “Bežanijska kosa”, Belgrade, Serbia
  • Dragomir Marisavljević Clinic for Hematology and Oncology, Medical Center “Bežanijska kosa”, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Nataša Stanisavljević Clinic for Hematology and Oncology, Medical Center “Bežanijska kosa”, Belgrade, Serbia
  • Biljana Mihaljević Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Clinic for Hematology, Clinical Center of Serbia, Belgrade, Serbia
  • Vladimir Kovčin Clinic for Hematology and Oncology, Medical Center “Bežanijska kosa”, Belgrade, Serbia
  • Olivera Marković Clinic for Hematology and Oncology, Medical Center “Bežanijska kosa”, Belgrade, Serbia
  • Radmila Živković Clinic for Hematology and Oncology, Medical Center “Bežanijska kosa”, Belgrade, Serbia
Ključne reči: lymphoma, b-cell, marginal zone||, ||limfom, malt, stomach neoplasms||, ||želudac, neoplazme, immunohistochemistry||, ||imunohistohemija, gene expression||, ||geni, ekspresija, signal transduction||, ||signali, transdukcija,

Sažetak


Uvod/Cilj. Limfomi limfnog tkiva pridruženog mukozi (MALT) čine 5–17% svih non-Hodgkin limfoma (NHL). Molekularna patogeneza MALT limfoma nije razjašnjena. Cilj ove studije bio je da se imunohistohemijski utvrdi prisustvo nuklearne koekspresije BCL10 i NF-kappaB (NF-κB) u tumorskim ćelijama želudačnog MALT limfoma kao i njihov uticaj na patogenezu i ishod bolesti. Metode. Analizirani su klinički podaci iz istorija bolesti 35 bolesnika sa novodijagnostikovanim želudačnim MALT limfomom i uzorci tkiva biopsije želuca bojeni su imunohistohemijskom metodom na ekspresiju BCL10 i NF-κB. Rezultati. Prosečna starost kod 35 bolesnika sa dijagnozom želudačnog MALT limfoma iznosila je 63,5 godina (muškarci/žene = 21/14). Simptomi su bili prisutni kod 23/35 (65,7%) bolesnika sa gubitkom težine kao najčešćim simptomom. Želudačni MALT limfom bio je najčešće lokalizovan u korpusu i korpusu i antrumu (45,7% i 31,2%). Infekcija H. pylori bila je potvrđena kod 20 od 30 (66,7%) bolesnika. Bolesnici su lečeni imunohemioterapijom (10 bolesnika, 28,5%), hirurški (9 bolesnika, 25,8%), kombinacijom hirurgije i hemioterapije (14 bolesnika, 40%) i suportivno (2 bolesnika, 5,7%). Kompletna remisija bila je postignuta kod 13 (37,1%) bolesnika, a parcijalna remisija kod dva (5,7%) bolesnika. Kod 16 (45,7%) bolesnika došlo je do progresije bolesti (p < 0,001). Citoplazmatska ekspresija BCL10 bila je nađena kod 19 (54,3%) tumorskih ćelija. Nuklearna ekspresija nije uočena ni u jednom uzorku. Citoplazmatska ekspresija NF-κB bila je prisutna u 22 (65,7%) uzorka, ali nuklearna ekspresija nije potvrđena ni u jednom uzorku. Zaključak. Nuklearna ekspresija (aktivacija) p65 subjedinice NF-κB puta i BCL10 nije otkrivena u uzorcima želudačnog MALT limfoma. Korelacija nuklearne koekspresije BCL10 i NF-κB u tumorskim ćelijama želudačnog MALT limfoma nije utvrđena. Ovi rezultati ukazuju da su neki drugi mehanizmi i signalni putevi aktivni u limfogenezi želudačnog MALT limfoma i da inhibicija apoptoze nije glavni i jedini mehanizam tumorogeneze.

Biografija autora

Jelena Hajder, Clinic for Hematology and Oncology, Medical Center “Bežanijska kosa”, Belgrade, Serbia
hematology

Reference

Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 1999; 17(12): 3835−49.

Thieblemont C. Clinical presentation and management of mar-ginal zone lymphomas. Hematology Am Soc Hematol Educ Program 2005: 307−13.

Ferrucci PF, Zucca E. Primary gastric lymphoma pathogenesis and treatment: what has changed over the past 10 years. Br J Haematol 2007; 136(4): 521−38.

Pozzi B, Cerati M, Capella C. MALT lymphoma: pathology. In: Bertoni F, Zucca E editor. MALT lymphomas. Georgetown (TX): Landes Bioscience/Kluwer Plenum Publishers; 2004. p. 17−38.

Thieblemont C, Coffier B. MALT lymphomas. Sites of Presenta-tions, Clinical features and Staging Procedures. In: : Bertoni F, Zucca E editor. MALT lymphomas. Georgetown (TX): Landes Bioscience/Kluwer Plenum Publishers; 2004. p. 60−80.

Katić V, Katić K, Vučetić M, Gligorijević J. The histopathology and immunohistology of gastric MALT lymphoma. Arch Oncol 2004; 12(1): 5−6.

Kahl BS. Update: gastric MAcLT lymphoma. Curr Opin Oncol 2003; 15: 347−52.

Nakagawa M, Hosokawa Y, Yonezumi M, Izumiyama K, Suzuki R, Tsuzuki S, et al. MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10. Blood 2005; 106(13): 4210−6.

Hachem A, Gartenhaus RB. Oncogenes as molecular targets in lymphoma. Blood 2005; 106(6): 1911−23.

Bugarski D, Petakov M, Vlaški M, Krstić A, Čokić V, Jovčić G, et al.. Mehanizmi prenosa signala u toku stimulacije matičnih ćelija hematopoeze. Bilten za hematologiju 2004; 32(3): 156−9. (Serbian)

Lucas PC, Yonezumi M, Inohara N, Mcallister-Lucas LM, Abazeed ME, Chen FF, et al. Bcl10 and MALT1, Independent Targets of Chromosomal Translocation in MALT Lymphoma, Cooperate in a Novel NF-kappa B Signaling Pathway. J Biol Chem 2001; 276(22): 19012−9.

Isaacson PG, Du M. MALT lymphoma: from morphology to molecules. Nat Rev Cancer 2004; 4(8): 644−53.

Ye H, Gong L, Liu H, Hamoudi RA, Shirali S, Ho L, et al.. MALT lymphoma with t(14;18)(q32;q21)/IGH-MALT1 is characterized by strong cytoplasmic MALT1 and BCL10 ex-pression. J Pathol 2005; 205(3): 293−301.

Bertoni F, Cotter F. MALT lymphomas. Genetics and Biology. In: Bertoni F, Zucca E editor. MALT lymphomas. Georgetown (TX): Landes Bioscience/Kluwer Plenum Publishers; 2004. p. 46−59.

Ye H, Dogan A, Karran L, Willis TG, Chen L, Wlodarska I, et al. BCL10 Expression in Normal and Neoplastic Lymphoid Tis-sue: Nuclear localisation in MALT lymphoma. Am J Pathol 2000; 157(4): 1147−54.

Cavalli F, Isaacson PG, Gascoyne RD, Zucca E. MALT Lympho-mas. Hematology Am Soc Hematol Educ Program 2001: 241−58.

Lui H, Ye H, Dogan A, Ranaldi R, Hamoudi RA, Bearzi I, et al. T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10. Blood 2001; 98(4): 1182−7.

Yeh KH, Kuo SH, Chen LT, Mao TL, Doong SL, Wu MS, et al. Nuclear expression of BCL10 or nuclear factor kappa B helps predict Helicobacter pylori-independent status of low-grade gastric mucosa-associated lymphoid tissue lymphomas with or without t(11;18)(q21;q21). Blood 2005; 106(3): 1037−41.

Franco R, Camacho FI, Caleo A, Staibano S, Bifano D, de Renzo A, et al. Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival. Mod Pathol 2006; 19(8): 1055−67.

Gilmore TD, Kalaitzidis D, Liang MC, Starczynowski DT. The c-Rel transcription factor and B-cell proliferation: a deal with the devil. Oncogene 2004; 23(13): 2275−86.

Talwalkar SS, Valbuena JR, Abruzzo LV, Admirand JH, Konoplev SN, Bueso-Ramos CE, et al. MALT1 gene rerrangements and NF-kappaB activation involving p65 and p50 are absent or rare in primary MALT lymphomas of the breast. Mod Pathol 2006; 19(11): 1402−8.

Sagaert X, Laurent M, Baens M, Wlodarska I, de Wolf-Peeters C. MALT1 and BCL10 aberrations in MALT lymphomas and their effect on the expression of BCL10 in the tumour cells. Mod Pathol 2006; 19(2): 225−32.

Sagaert X, de Wolf-Peeters C, Noels H, Baens M. The pathogenesis of MALT lymphomas: where do we stand. Leukemia 2007; 21(3): 389−96.

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2015/04/24
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