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Published in: Tumor Biology 5/2011

01-10-2011 | Research Article

Expression of PIK3CA and FOXP1 in gastric and intestinal non-Hodgkin’s lymphoma of mucosa-associated lymphoid tissue type

Authors: Linzhu Zhai, Yuanyuan Zhao, Sheng Ye, He Huang, Ying Tian, Qiuliang Wu, Hanliang Lin, Tongyu Lin

Published in: Tumor Biology | Issue 5/2011

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Abstract

Non-Hodgkin’s lymphoma of mucosa-associated lymphoid tissue (MALT) type arises from a wide variety of extranodal sites, most frequently from the gastrointestinal tract. Recently, it has been demonstrated that karyotypic alterations involving the PIK3CA and FOXP1 genes of chromosome 3 occur in MALT lymphoma. However, their associated protein expression has not been extensively studied. Tumor tissues from 27 gastric and 23 intestinal MALT lymphomas were analyzed for PIK3CA and FOXP1 protein expression using immunohistochemistry and correlated with histological features and treatment outcomes. Expression of PIK3CA, a novel indicator, was found in 40% of gastrointestinal cases and indicated an inferior progression-free survival in both gastric and intestinal MALT lymphomas (P = 0.001 and P = 0.015). Tumor staining of nuclear FOXP1 (46.0%) was more common in gastric than intestinal MALT lymphomas (P = 0.042) and was significantly associated with polymorphic histology (P = 0.007). FOXP1 expression was identified as an adverse prognostic factor for overall survival in gastric MALT lymphomas (P = 0.035). We further combined these two markers and observed that patients that are positive for both PIK3CA and FOXP1 had a worse overall and progression-free survival. Considering the small sample size of this study, these results should be confirmed in a large prospective study.
Literature
1.
go back to reference The Non-Hodgkin's Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. Blood. 1997;89(11):3909–18. The Non-Hodgkin's Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. Blood. 1997;89(11):3909–18.
2.
go back to reference Cavalli F, Isaacson PG, Gascoyne RD, Zucca E. MALT lymphomas. Hematology Am Soc Hematol Educ Program 2004;241–258 Cavalli F, Isaacson PG, Gascoyne RD, Zucca E. MALT lymphomas. Hematology Am Soc Hematol Educ Program 2004;241–258
3.
go back to reference Raderer M, Streubel B, Woehrer S, Puespoek A, Jaeger U, Formanek M, et al. High relapse rate in patients with MALT lymphoma warrants lifelong follow-up. Clin Cancer Res. 2005;11(9):3349–52.PubMedCrossRef Raderer M, Streubel B, Woehrer S, Puespoek A, Jaeger U, Formanek M, et al. High relapse rate in patients with MALT lymphoma warrants lifelong follow-up. Clin Cancer Res. 2005;11(9):3349–52.PubMedCrossRef
4.
go back to reference Starostik P, Patzner J, Greiner A, Schwarz S, Kalla J, Ott G, et al. Gastric marginal zone B-cell lymphomas of MALT type develop along 2 distinct pathogenetic pathways. Blood. 2002;99(1):3–9.PubMedCrossRef Starostik P, Patzner J, Greiner A, Schwarz S, Kalla J, Ott G, et al. Gastric marginal zone B-cell lymphomas of MALT type develop along 2 distinct pathogenetic pathways. Blood. 2002;99(1):3–9.PubMedCrossRef
5.
go back to reference Streubel B, Vinatzer U, Lamprecht A, Raderer M, Chott A. T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma. Leukemia. 2005;19(4):652–8.PubMed Streubel B, Vinatzer U, Lamprecht A, Raderer M, Chott A. T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma. Leukemia. 2005;19(4):652–8.PubMed
6.
go back to reference Wotherspoon AC, Finn TM, Isaacson PG. Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue. Blood. 1995;85(8):2000–4.PubMed Wotherspoon AC, Finn TM, Isaacson PG. Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue. Blood. 1995;85(8):2000–4.PubMed
7.
go back to reference Krugmann J, Tzankov A, Dirnhofer S, Fend F, Wolf D, Siebert R, et al. Complete or partial trisomy 3 in gastro-intestinal MALT lymphomas co-occurs with aberrations at 18q21 and correlates with advanced disease stage: a study on 25 cases. World J Gastroenterol. 2005;11(46):7384–5.PubMed Krugmann J, Tzankov A, Dirnhofer S, Fend F, Wolf D, Siebert R, et al. Complete or partial trisomy 3 in gastro-intestinal MALT lymphomas co-occurs with aberrations at 18q21 and correlates with advanced disease stage: a study on 25 cases. World J Gastroenterol. 2005;11(46):7384–5.PubMed
8.
go back to reference Dierlamm J, Pittaluga S, Wlodarska I, Stul M, Thomas J, Boogaerts M, et al. Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features. Blood. 1996;87(1):299–307.PubMed Dierlamm J, Pittaluga S, Wlodarska I, Stul M, Thomas J, Boogaerts M, et al. Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features. Blood. 1996;87(1):299–307.PubMed
9.
go back to reference Barrans SL, Fenton JA, Banham A, Owen RG, Jack AS. Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome. Blood. 2004;104(9):2933–5.PubMedCrossRef Barrans SL, Fenton JA, Banham A, Owen RG, Jack AS. Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome. Blood. 2004;104(9):2933–5.PubMedCrossRef
10.
go back to reference Banham AH, Connors JM, Brown PJ, Cordell JL, Ott G, Sreenivasan G, et al. Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma. Clin Cancer Res. 2005;11(3):1065–72.PubMed Banham AH, Connors JM, Brown PJ, Cordell JL, Ott G, Sreenivasan G, et al. Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma. Clin Cancer Res. 2005;11(3):1065–72.PubMed
11.
go back to reference Akagi I, Miyashita M, Makino H, Nomura T, Hagiwara N, Takahashi K, et al. Overexpression of PIK3CA is associated with lymph node metastasis in esophageal squamous cell carcinoma. Int J Oncol. 2009;34(3):767–75.PubMedCrossRef Akagi I, Miyashita M, Makino H, Nomura T, Hagiwara N, Takahashi K, et al. Overexpression of PIK3CA is associated with lymph node metastasis in esophageal squamous cell carcinoma. Int J Oncol. 2009;34(3):767–75.PubMedCrossRef
12.
go back to reference Wang Y, Kristensen GB, Helland A, Nesland JM, Borresen-Dale AL, Holm R. Protein expression and prognostic value of genes in the erb-b signaling pathway in advanced ovarian carcinomas. Am J Clin Pathol. 2005;124(3):392–401.PubMedCrossRef Wang Y, Kristensen GB, Helland A, Nesland JM, Borresen-Dale AL, Holm R. Protein expression and prognostic value of genes in the erb-b signaling pathway in advanced ovarian carcinomas. Am J Clin Pathol. 2005;124(3):392–401.PubMedCrossRef
13.
go back to reference Zelenetz AD, Chen TT, Levy R. Histologic transformation of follicular lymphoma to diffuse lymphoma represents tumor progression by a single malignant B cell. J Exp Med. 1991;173(1):197–207.PubMedCrossRef Zelenetz AD, Chen TT, Levy R. Histologic transformation of follicular lymphoma to diffuse lymphoma represents tumor progression by a single malignant B cell. J Exp Med. 1991;173(1):197–207.PubMedCrossRef
14.
go back to reference Kluin PM, van Krieken JH, Kleiverda K, Kluin-Nelemans HC. Discordant morphologic characteristics of B-cell lymphomas in bone marrow and lymph node biopsies. Am J Clin Pathol. 1990;94(1):59–66.PubMed Kluin PM, van Krieken JH, Kleiverda K, Kluin-Nelemans HC. Discordant morphologic characteristics of B-cell lymphomas in bone marrow and lymph node biopsies. Am J Clin Pathol. 1990;94(1):59–66.PubMed
15.
go back to reference McCormick C, Philp E, Mansi J, Livni N, McCarthy K. Clonal analysis of three morphologically distinct lymphomas occurring in the same patient. J Clin Pathol. 1994;47(11):1038–42.PubMedCrossRef McCormick C, Philp E, Mansi J, Livni N, McCarthy K. Clonal analysis of three morphologically distinct lymphomas occurring in the same patient. J Clin Pathol. 1994;47(11):1038–42.PubMedCrossRef
16.
go back to reference Chan JK. The new World Health Organization classification of lymphomas: the past, the present and the future. Hematol Oncol. 2001;19(4):129–50.PubMedCrossRef Chan JK. The new World Health Organization classification of lymphomas: the past, the present and the future. Hematol Oncol. 2001;19(4):129–50.PubMedCrossRef
17.
go back to reference Ferreri AJ, Freschi M, Dell'Oro S, Viale E, Villa E, Ponzoni M. Prognostic significance of the histopathologic recognition of low- and high-grade components in stage I-II B-cell gastric lymphomas. Am J Surg Pathol. 2001;25(1):95–102.PubMedCrossRef Ferreri AJ, Freschi M, Dell'Oro S, Viale E, Villa E, Ponzoni M. Prognostic significance of the histopathologic recognition of low- and high-grade components in stage I-II B-cell gastric lymphomas. Am J Surg Pathol. 2001;25(1):95–102.PubMedCrossRef
18.
go back to reference de Jong D, Boot H, van Heerde P, Hart GA, Taal BG. Histological grading in gastric lymphoma: pretreatment criteria and clinical relevance. Gastroenterology. 1997;112(5):1466–74.PubMedCrossRef de Jong D, Boot H, van Heerde P, Hart GA, Taal BG. Histological grading in gastric lymphoma: pretreatment criteria and clinical relevance. Gastroenterology. 1997;112(5):1466–74.PubMedCrossRef
19.
go back to reference Hsi ED, Eisbruch A, Greenson JK, Singleton TP, Ross CW, Schnitzer B. Classification of primary gastric lymphomas according to histologic features. Am J Surg Pathol. 1998;22(1):17–27.PubMedCrossRef Hsi ED, Eisbruch A, Greenson JK, Singleton TP, Ross CW, Schnitzer B. Classification of primary gastric lymphomas according to histologic features. Am J Surg Pathol. 1998;22(1):17–27.PubMedCrossRef
20.
go back to reference Rohatiner A, d'Amore F, Coiffier B, Crowther D, Gospodarowicz M, Isaacson P, et al. Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Ann Oncol. 1994;5((5):397–400.PubMed Rohatiner A, d'Amore F, Coiffier B, Crowther D, Gospodarowicz M, Isaacson P, et al. Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Ann Oncol. 1994;5((5):397–400.PubMed
21.
go back to reference Zucca E, Conconi A, Pedrinis E, Cortelazzo S, Motta T, Gospodarowicz MK, et al. Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Blood. 2003;101(7):2489–95.PubMedCrossRef Zucca E, Conconi A, Pedrinis E, Cortelazzo S, Motta T, Gospodarowicz MK, et al. Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Blood. 2003;101(7):2489–95.PubMedCrossRef
22.
go back to reference Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275–82.PubMedCrossRef Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275–82.PubMedCrossRef
23.
go back to reference Hoefnagel JJ, Mulder MM, Dreef E, Jansen PM, Pals ST, Meijer CJ, et al. Expression of B-cell transcription factors in primary cutaneous B-cell lymphoma. Mod Pathol. 2006;19(9):1270–6.PubMedCrossRef Hoefnagel JJ, Mulder MM, Dreef E, Jansen PM, Pals ST, Meijer CJ, et al. Expression of B-cell transcription factors in primary cutaneous B-cell lymphoma. Mod Pathol. 2006;19(9):1270–6.PubMedCrossRef
24.
go back to reference Kang S, Bader AG, Vogt PK. Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci USA. 2005;102(3):802–7.PubMedCrossRef Kang S, Bader AG, Vogt PK. Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci USA. 2005;102(3):802–7.PubMedCrossRef
25.
go back to reference Baohua Y, Xiaoyan Z, Tiecheng Z, Tao Q, Daren S. Mutations of the PIK3CA gene in diffuse large B cell lymphoma. Diagn Mol Pathol. 2008;17(3):159–65.PubMedCrossRef Baohua Y, Xiaoyan Z, Tiecheng Z, Tao Q, Daren S. Mutations of the PIK3CA gene in diffuse large B cell lymphoma. Diagn Mol Pathol. 2008;17(3):159–65.PubMedCrossRef
26.
go back to reference Rudelius M, Pittaluga S, Nishizuka S, Pham TH, Fend F, Jaffe ES, et al. Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma. Blood. 2006;108(5):1668–76.PubMedCrossRef Rudelius M, Pittaluga S, Nishizuka S, Pham TH, Fend F, Jaffe ES, et al. Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma. Blood. 2006;108(5):1668–76.PubMedCrossRef
27.
go back to reference Miletic AV, Anzelon-Mills AN, Mills DM, Omori SA, Pedersen IM, Shin DM, et al. Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases. J Exp Med. 2010;207(11):2407–20.PubMedCrossRef Miletic AV, Anzelon-Mills AN, Mills DM, Omori SA, Pedersen IM, Shin DM, et al. Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases. J Exp Med. 2010;207(11):2407–20.PubMedCrossRef
28.
go back to reference Kuo SH, Yeh PY, Chen LT, Wu MS, Lin CW, Yeh KH, et al. Overexpression of B cell-activating factor of TNF family (BAFF) is associated with Helicobacter pylori-independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma. Blood. 2008;112(7):2927–34.PubMedCrossRef Kuo SH, Yeh PY, Chen LT, Wu MS, Lin CW, Yeh KH, et al. Overexpression of B cell-activating factor of TNF family (BAFF) is associated with Helicobacter pylori-independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma. Blood. 2008;112(7):2927–34.PubMedCrossRef
29.
go back to reference Karakas B, Bachman KE, Park BH. Mutation of the PIK3CA oncogene in human cancers. Br J Cancer. 2006;94(4):455–9.PubMedCrossRef Karakas B, Bachman KE, Park BH. Mutation of the PIK3CA oncogene in human cancers. Br J Cancer. 2006;94(4):455–9.PubMedCrossRef
30.
go back to reference Bousquet M, Recher C, Queleen C, Demur C, Payrastre B, Brousset P. Assessment of somatic mutations in phosphatidylinositol 3-kinase gene in human lymphoma and acute leukaemia. Br J Haematol. 2005;131(3):411–3.PubMedCrossRef Bousquet M, Recher C, Queleen C, Demur C, Payrastre B, Brousset P. Assessment of somatic mutations in phosphatidylinositol 3-kinase gene in human lymphoma and acute leukaemia. Br J Haematol. 2005;131(3):411–3.PubMedCrossRef
31.
go back to reference Woenckhaus J, Steger K, Werner E, Fenic I, Gamerdinger U, Dreyer T, et al. Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma. J Pathol. 2002;198(3):335–42.PubMedCrossRef Woenckhaus J, Steger K, Werner E, Fenic I, Gamerdinger U, Dreyer T, et al. Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma. J Pathol. 2002;198(3):335–42.PubMedCrossRef
32.
go back to reference Zhai LZ, Huang Y, Wang SS, Cao YB, Xiao J, Fu X, et al. PIK3CA, BCL-6, MLL and FOXP1 in the transformation and prognosis of MALT lymphoma [abstract]. J Clin Oncol. 2008;26(May 20 suppl):abstr 8577. Zhai LZ, Huang Y, Wang SS, Cao YB, Xiao J, Fu X, et al. PIK3CA, BCL-6, MLL and FOXP1 in the transformation and prognosis of MALT lymphoma [abstract]. J Clin Oncol. 2008;26(May 20 suppl):abstr 8577.
33.
go back to reference Carlsson P, Mahlapuu M. Forkhead transcription factors: key players in development and metabolism. Dev Biol. 2002;250(1):1–23.PubMedCrossRef Carlsson P, Mahlapuu M. Forkhead transcription factors: key players in development and metabolism. Dev Biol. 2002;250(1):1–23.PubMedCrossRef
34.
go back to reference Nakamura S, Ye H, Bacon CM, Goatly A, Liu H, Banham AH, et al. Clinical impact of genetic aberrations in gastric MALT lymphoma: a comprehensive analysis using interphase fluorescence in situ hybridisation. Gut. 2007;56(10):1358–63.PubMedCrossRef Nakamura S, Ye H, Bacon CM, Goatly A, Liu H, Banham AH, et al. Clinical impact of genetic aberrations in gastric MALT lymphoma: a comprehensive analysis using interphase fluorescence in situ hybridisation. Gut. 2007;56(10):1358–63.PubMedCrossRef
35.
go back to reference Han SL, Wu XL, Wan L, Zeng QQ, Li JL, Liu Z. FOXP1 expression predicts polymorphic histology and poor prognosis in gastric mucosa-associated lymphoid tissue lymphomas. Dig Surg. 2009;26(2):156–62.PubMedCrossRef Han SL, Wu XL, Wan L, Zeng QQ, Li JL, Liu Z. FOXP1 expression predicts polymorphic histology and poor prognosis in gastric mucosa-associated lymphoid tissue lymphomas. Dig Surg. 2009;26(2):156–62.PubMedCrossRef
36.
go back to reference Sagaert X, de Paepe P, Libbrecht L, Vanhentenrijk V, Verhoef G, Thomas J, et al. Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(16):2490–7.PubMedCrossRef Sagaert X, de Paepe P, Libbrecht L, Vanhentenrijk V, Verhoef G, Thomas J, et al. Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(16):2490–7.PubMedCrossRef
37.
go back to reference Farinha P, Gascoyne RD. Molecular pathogenesis of mucosa-associated lymphoid tissue lymphoma. J Clin Oncol. 2005;23(26):6370–8.PubMedCrossRef Farinha P, Gascoyne RD. Molecular pathogenesis of mucosa-associated lymphoid tissue lymphoma. J Clin Oncol. 2005;23(26):6370–8.PubMedCrossRef
38.
go back to reference Goatly A, Bacon CM, Nakamura S, Ye H, Kim I, Brown PJ, et al. FOXP1 abnormalities in lymphoma: translocation breakpoint mapping reveals insights into deregulated transcriptional control. Mod Pathol. 2008;21(7):902–11.PubMedCrossRef Goatly A, Bacon CM, Nakamura S, Ye H, Kim I, Brown PJ, et al. FOXP1 abnormalities in lymphoma: translocation breakpoint mapping reveals insights into deregulated transcriptional control. Mod Pathol. 2008;21(7):902–11.PubMedCrossRef
Metadata
Title
Expression of PIK3CA and FOXP1 in gastric and intestinal non-Hodgkin’s lymphoma of mucosa-associated lymphoid tissue type
Authors
Linzhu Zhai
Yuanyuan Zhao
Sheng Ye
He Huang
Ying Tian
Qiuliang Wu
Hanliang Lin
Tongyu Lin
Publication date
01-10-2011
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2011
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-011-0192-3

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