Top

Published in:

01-12-2012 | Original Article

Impact of proliferative indices and tumor suppressor genes on treatment response in marginal zone lymphomas

Authors: Mohammad Hussaini, Friederike Kreisel, Anjum Hassan

Published in: Comparative Clinical Pathology | Issue 6/2012

Abstract

Firstly, increased Ki67 and MUM-1 staining has been associated with worse prognosis in marginal zone B cell lymphomas (MZL). However, ours is the first study to assess the impact of proliferative indices on chemotherapy response. Secondly, loss of p53 and p16 tumor suppressor genes (TSG) has traditionally been associated with cancer progression. The significance of these markers in MZL was investigated. Thirdly, we explored the role of proliferative indices and tumor suppressor genes in identifying MZLs with significant plasmacytic differentiation (PD). Consecutive MZL cases (2006–2008) were identified. Slides were reviewed to confirm the diagnosis; immunohistochemical stains for Ki67, MUM-1, WT-1, p53, and p16 were subsequently performed and graded for percentage staining. Wilcoxon two-sample test and Pearson correlation coefficient were performed. Twenty-nine cases were analyzed. None of the assayed markers were correlated with treatment response. Ki67 and MUM1 expression, however, were correlated with PD (p = 0.0136 and p = 0.0042). A correlation between MUM1 and p16 staining was also seen (p = 0.0006). IHC assay for TSGs, p53 and p16, and proliferative indices (Ki67, MUM1, WT1) is unlikely to predict treatment response in low-grade MZL. Ki67 and MUM1 staining, however, may serve as a useful adjunct in ascribing PD.

Aleman BM, Haas RL, van der Maazen RW (2010) Role of radiotherapy in the treatment of lymphomas of the gastrointestinal tract. Best Pract Res Clin Gastroenterol 24(1):27–34PubMedCrossRef

Baldini L, Guffanti A, Cro L, Fracchiolla NS, Colombi M, Motta M et al (1997) Poor prognosis in non-villous splenic marginal zone cell lymphoma is associated with p53 mutations. Br J Haematol 99(2):375–378PubMedCrossRef

Bennett M, Schechter GP (2010) Treatment of splenic marginal zone lymphoma: splenectomy versus rituximab. Semin Hematol 47(2):143–147PubMedCrossRef

Berger F, Felman P, Thieblemont C, Pradier T, Baseggio L, Bryon PA et al (2000) Non-MALT marginal zone B-cell lymphomas: a description of clinical presentation and outcome in 124 patients. Blood 95(6):1950–1956PubMed

Brown JR, Friedberg JW, Feng Y, Scofield S, Phillips K, Dal Cin P et al (2009) A phase 2 study of concurrent fludarabine and rituximab for the treatment of marginal zone lymphomas. Br J Haematol 146(6):685–686CrossRef

Bryant RJ, Banks PM, O'Malley DP (2006) Ki67 staining pattern as a diagnostic tool in the evaluation of lymphoproliferative disorders. Histopathology 48(5):505–515PubMedCrossRef

Camacho FI, Mollejo M, Mateo MS, Algara P, Navas C, Hernández JM et al (2001) Progression to large B-cell lymphoma in splenic marginal zone lymphoma: a description of a series of 12 cases. Am J Surg Pathol 25(10):1268–1276PubMedCrossRef

Chacón JI, Mollejo M, Muñoz E, Algara P, Mateo M, Lopez L et al (2002) Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 60 patients. Blood 100(5):1648–1654PubMed

Du MQ, Isaccson PG (2002) Gastric MALT lymphoma: from aetiology to treatment. Lancet Oncol 3(2):97–104PubMedCrossRef

Du M, Singh N, Husseuin A, Isaacson PG, Pan L et al (1996) Positive correlation between apoptotic and proliferative indices in gastrointestinal lymphomas of mucosa-associated lymphoid tissue (MALT). J Pathol 178(4):379–384PubMedCrossRef

Federico M, Molica S, Bellei M, Luminari S (2009) Prognostic factors in low-grade non-Hodgkin lymphomas. Curr Hematol Malig Rep 4:202–210PubMedCrossRef

Franco R, Camacho FI, Caleo A, Staibano S, Bifano D, De Renzo A et al (2006) Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival. Mod Pathol 19(8):1055–1067PubMed

Gruszka-Westwood AM, Hamoudi RA, Matutes E, Tuset E, Catovsky D (2001) p53 abnormalities in splenic lymphoma with villous lymphocytes. Blood 97(11):3552–3558PubMedCrossRef

Hunter T, Pines J (1994) Cyclins and cancer II: cyclin D and CDK inhibitors come of age. Cell 79:573–582PubMedCrossRef

Imamura J, Miyashi I, Koeffler PH (1994) P53 in haematologic malignancies. Blood 84:2412–2421PubMed

Insabato L, Di Vizio D, Tornillo L, D'Armiento FP, Siciliano A, Milo M et al (2003) Clinicopathologic and immunohistochemical study of surgically treated primary gastric MALT lymphoma. J Surg Oncol 83(2):106–111PubMedCrossRef

Kato H, Miyazaki T, Fukai Y, Nakajima M, Sohda M, Takita J et al (2003) A new proliferation marker, minichromosome maintenance protein 2, is associated with tumor aggressiveness in esophageal squamous cell carcinoma. J Surg Oncol 84(1):24–30PubMedCrossRef

Kovalevska LM, Yurchenko OV, Shlapatska LM, Berdova GG, Mikhalap SV, Van Lint J et al (2006) Immunohistochemical studies of protein kinase D (PKD) 2 expression in malignant human lymphomas. Exp Oncol 28(3):225–230PubMed

Li HL, Sun BZ, Ma FC (2004) Expression of COX-2, iNOS, p53 and Ki-67 in gastric mucosa-associated lymphoid tissue lymphoma. World J Gastroenterol 10(13):1862–1866PubMed

Liggett WH, Sidransky D (1998) Role of the p16 tumor suppressor gene in cancer. J Clin Oncol 16(3):1197–1206PubMed

Menssen HD, Renkl HJ, Rodeck U, Kari C, Schwartz S, Thiel E (1997) Detection by monoclonal antibodies of the Wilms' tumor (WT1) nuclear protein in patients with acute leukemia. Int J Cancer 70(5):518–523PubMedCrossRef

Olszewski M, Huang W, Chou PM, Duerst R, Kletzel M (2005) Wilms' tumor 1 (WT1) gene in hematopoiesis: a surrogate marker of cell proliferation as a possible mechanism of action? Cytotherapy 7(1):57–61PubMedCrossRef

Paterlini P, Suberville AM, Zindy F, Melle J, Sonnier M, Marie JP et al (1993) Cyclin A expression in human hematological malignancies: a new marker of cell proliferation. Cancer Res 53(2):235–238PubMed

Petit B, Chaury MP, Le Clorennec C, Jaccard A, Gachard N, Moalic-Judge S et al (2005) Indolent lymphoplasmacytic and marginal zone B-cell lymphomas: absence of both IRF4 and Ki67 expression identifies a better prognosis subgroup. Haematologica 90(2):200–206PubMed

Raderer M, Paul de Boer J (2004) Role of chemotherapy in gastric MALT lymphoma, diffuse large B-cell lymphoma and other lymphomas. Best Pract Res Clin Gastroenterol 24(1):19–26CrossRef

Rose DS, Maddox PH, Brown DC (1994) Which proliferation markers for routine immunohistology? A comparison of five antibodies. J Clin Pathol 47:1010–1014PubMedCrossRef

Ruiz-Ballesteros E, Mollejo M, Rodriguez A, Camacho FI, Algara P, Martinez N et al (2005) Splenic marginal zone lymphoma: proposal of new diagnostic and prognostic markers identified after tissue and cDNA microarray analysis. Blood 106(5):1831–1838PubMedCrossRef

Schrader C, Meusers P, Brittinger G, Teymoortash A, Siebmann JU, Janssen D et al (2004) Topoisomerase II expression in mantle cell lymphoma: a marker of cell proliferation and a prognostic factor for clinical outcome. Leukemia 18:1200–1206PubMedCrossRef

Sharpless NE, Alson S, Chan S, Silver DP, Castrillon DH, DePinho RA (2002) p16(INK4a) and p53 deficiency cooperate in tumorigenesis. Cancer Res 62(10):2761–2765PubMed

Smith-Ravin J, Spencer J, Beverley PC, Isaacson PG (1990) Characterization of two monoclonal antibodies (UCL4D12 and UCL3D3) that discriminate between human mantle zone and marginal zone B cells. Clin Exp Immunol 82:181–187PubMedCrossRef

Spencer J, Perry ME, Dunn-Walters D (1998) Human marginal-zone B cells. Immunol Today 19(9):421–426PubMedCrossRef

Stefanaki K, Tzardi M, Kouvidou C, Chaniotis V, Bolioti M, Vlychou M et al (1998) Expression of p53, p21, mdm2, Rb, bax and Ki67 proteins in lymphomas of the mucosa-associated lymphoid (MALT) tissue. Anticancer Res 18(4A):2403–2408PubMed

Sundram U, Harvell JD, Rouse RV, Natkunam Y (2003) Expression of the B-cell proliferation marker MUM1 by melanocytic lesions and comparison with S100, gp100 (HMB45), and MelanA. Mod Pathol 16(8):802–810PubMedCrossRef

Suzuki H, Saito Y, Hibi T (2009) Helicobacter pylori and gastric mucosa-associated lymphoid tissue (MALT) lymphoma: updated review of clinical outcomes and the molecular pathogenesis. Gut Liver 3(2):81–87PubMedCrossRef

Swanson S, Brooks J (1990) Proliferation markers Ki-67 and p105 in soft-tissue lesions. Correlation with DNA flow cytometric characteristics. Am J Pathol 137(6):1491–1500PubMed

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al (2008) WHO classification of tumors and haematopoeitic and lymphoid tissues. IARC, Lyon

Timár J, Mészáros L, Orosz Z, Albini A, Rásó E (2005) WT1 expression in angiogenic tumours of the skin. Histopathology 47:67–73PubMedCrossRef

Wohlschlegel JA, Kutok JL, Weng AP, Dutta A (2002) Expression of geminin as a marker of cell proliferation in normal tissues and malignancies. Am J Pathol 161(1):267–273PubMedCrossRef

Wołowiec D, Deviller P, Simonin D, Souchier C, Rimokh R, Benchaib M et al (1995) Cdk1 is a marker of proliferation in human lymphoid cells. Int J Cancer 61(3):381–388PubMedCrossRef

Wündisch T, Thiede C, Morgner A, Dempfle A, Günther A, Liu H et al (2005) Long-term follow-up of gastric MALT lymphoma after Helicobacter pylori eradication. J Clin Oncol 23:8018–8024PubMedCrossRef

Title: Impact of proliferative indices and tumor suppressor genes on treatment response in marginal zone lymphomas
Authors: Mohammad Hussaini
Friederike Kreisel
Anjum Hassan
Publication date: 01-12-2012
Publisher: Springer-Verlag
Published in: Comparative Clinical Pathology / Issue 6/2012
Print ISSN: 1618-5641
Electronic ISSN: 1618-565X
DOI: https://doi.org/10.1007/s00580-011-1271-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Impact of proliferative indices and tumor suppressor genes on treatment response in marginal zone lymphomas

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2012

Egg yolk: a model for screening compounds with potent antioxidants in foodstuff

Hematology of the Mediterranean population of sea turtle (Caretta caretta): comparison of blood values in wild and captive, juvenile and adult animals

Testicular morphology and antispermatogenic effects of 2,4-dichlorophenoxyacetic acid (2,4-D) in male West African Dwarf (WAD) goats

Anti-diabetic effect of Semecarpus anacardium Linn nut milk extract in a high fat diet STZ-induced type 2 diabetic rat model

Acute and subacute toxicity of chloroform and hexaneextracts of root of Xanthium strumarium

Supernumerary ectopic limb in lamb: a case report