BCL10 aberations and NF-kappa B activation involving p65 are absent or rare in primary gastric MALT lymphoma

Jelena Hajder; Dragomir Marisavljević; Nataša Stanisavljević; Biljana Mihaljević; Vladimir Kovčin; Olivera Marković; Radmila Živković

doi:10.2298/2389

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

DOI: https://doi.org/10.2298/2389

Keywords: lymphoma, b-cell, marginal zone, stomach neoplasms, immunohistochemistry, gene expression, signal transduction,

Abstract

Bacground/Aim. Mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 5–17% non-Hodgkin lymphomas (NHL). The molecular pathogenesis of MALT lymphomas is not well-established. The aim of this study was to evaluate immunohistochemically determined nuclear coexpression of BCL10 and NF-kappaB (NF-κB) in tumor cells of gastric MALT lymphoma and its impact on the patogenesis and outcome of the disease. Methods. Medical records of 35 patients with newly diagnosed gastric MALT lymphoma were analyzed and biopsy specimens were immunostained for BCL10 and NF-kB expression (p65 subunit). Results. The median age of 35 patients diagnosed with gastric MALT lymphoma was 63.5 years (male/female = 21/14). Symptoms were present in 23/35 (65.7%) patients with the weight loss as the most common symptom. Gastric MALT lymphomas were usually localized in the stomach corpus and corpus and antrum (45.7% and 31.2%, respectively). H. pylori infection was confirmed in 20 out of 30 (66.7%) patients. Treatment options were as follows: immunochemotherapy in 10 (28.5%) patients, surgery in 9 (25.8%) patients, combined surgery and chemotherapy in 14 (40%) patients and supportive measures in 2 (5.7%) patients. Complete remission was achieved in 13 (37.1%) patients and partial remission in two (5.7%) patients. Sixteen (45.7%) patients had disease progression (p < 0.001). Cytoplasmatic expression of BCL10 in tumor cells was detected in 19 (54.3%) specimens. Nuclear expression was detected in no specimen. Cytoplasmic expression of NF- κB was present in 22 (65.7%) specimens, but nuclear expression was not detected in any specimens. Conclusion. Nuclear expressions (activation) of NF-κB p65 subunit and BCL10 were not detected in specimens of gastric MALT lymphoma. The correlation of nuclear coexpression of BCL10 and NF-κB in gastric MALT lymphoma was not established. These results indicate that other mechanisms and signal pathways are active in lymphogenesis of gastric MALT lymphoma, as that apoptotic inhibition is not the main, nor the only mechanism in tumorogenesis.

Author Biography

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

no conflict of interest

References

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.