nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.09.2008 | Original Paper

Prognostic value of Bmi-1 oncoprotein expression in NSCLC patients: a tissue microarray study

verfasst von: Katerina Vrzalikova, Joseph Skarda, Jiri Ehrmann, Paul G. Murray, Eduard Fridman, Jury Kopolovic, Petra Knizetova, Marian Hajduch, Jiri Klein, Vitezslav Kolek, Lenka Radova, Zdenek Kolar

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2008

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Bmi-1 is a Polycomb group member which participates in many physiological processes as well as in a wide spectrum of cancers. The aim of this study was to investigate Bmi-1 expression in non-small cell lung cancer (NSCLC) in respect to clinicopathological features and therapeutic outcomes.

Methods

Immunohistochemical staining for Bmi-1 was performed on tissue microarrays (TMAs) constructed from 179 formalin-fixed and paraffin-embedded NSCLC samples (106 squamous, 58 adeno-, and 15 large cell carcinomas). Data were subject to statistical analysis by SPSS.

Results

Overall evaluation of all tumor cases showed that 20 (11.43%) were negative, 37 (21.14%) showed weak, 65 (37.14%) moderate and 57 (32.57%) strong nuclear positivity for Bmi-1. Statistical analysis of our data revealed that the expression of Bmi-1 was significantly higher in stage III (P = 10⁻⁶) and stage IV (P = 10⁻⁵) tumors compared to stages I and II tumors. The administration of adjuvant chemotherapy significantly increased DFS at stage I and II patients who did not express Bmi-1 when compared to their Bmi-1 positive counterparts (P = 0.05).

Conclusions

Our results suggest that Bmi-1 is significantly associated with progression of NSCLC and might serve as a prognostic marker of adverse disease outcome.

Bea S, Tort F, Pinyol M et al (2001) BMI-1 gene amplification and overexpression in hematological malignancies occur mainly in mantle cell lymphomas. Cancer Res 61:2409–2412PubMed

Breuer RH, Snijders PJ, Smit EF et al (2004) Increased expression of the EZH2 polycomb group gene in BMI-1-positive neoplastic cells during bronchial carcinogenesis. Neoplasia 6:736–743PubMedCrossRef

Breuer RH, Snijders PJ, Sutedja GT et al (2005) Expression of the p16(INK4a) gene product, methylation of the p16(INK4a) promoter region and expression of the polycomb-group gene BMI-1 in squamous cell lung carcinoma and premalignant endobronchial lesions. Lung Cancer 48:299–306PubMedCrossRef

Broers JL, Viallet J, Jensen SM et al (1993) Expression of c-myc in progenitor cells of the bronchopulmonary epithelium and in a large number of non-small cell lung cancers. Am J Respir Cell Mol Biol 9:33–43PubMed

Bruggeman SW, Valk-Lingbeek ME, van der Stoop PP et al (2005) Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice. Genes Dev 19:1438–1443PubMedCrossRef

Denlinger CE, Rundall BK, Jones DR (2004) Modulation of antiapoptotic cell signaling pathways in non-small cell lung cancer: the role of NF-kappaB. Semin Thorac Cardiovasc Surg 16:28–39PubMedCrossRef

Dimri GP, Martinez JL, Jacobs JJ et al (2002) The Bmi-1 oncogene induces telomerase activity and immortalizes human mammary epithelial cells. Cancer Res 62:4736–4745PubMed

Doyle LA (1993) Mechanisms of drug resistance in human lung cancer cells. Semin Oncol 20:326–337PubMed

Dubey S, Schiller JH (2005) Three emerging new drugs for NSCLC: pemetrexed, bortezomib, and cetuximab. Oncologist 10:282–291PubMedCrossRef

Dukers DF, van Galen JC, Giroth C et al (2004) Unique polycomb gene expression pattern in Hodgkin’s lymphoma and Hodgkin’s lymphoma-derived cell lines. Am J Pathol 164:873–881PubMed

Dutton A, Woodman C, Chukwuma M et al (2007) Bmi-1 is induced by the Epstein-Barr virus oncogene LMP1 and regulates the expression of viral target genes in Hodgkin lymphoma cells. Blood 109:2597–2603PubMedCrossRef

Glinsky GV, Berezovska O, Glinskii AB (2005) Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest 115:1503–1521PubMedCrossRef

Guney I, Wu S, Sedivy JM (2006) Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and p16 (INK4a). Proc Natl Acad Sci USA 103:3645–3650PubMedCrossRef

Iwama A, Oguro H, Negishi M et al (2004) Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity 21:843–851PubMedCrossRef

Jemal A, Tiwari RC, Murray T et al (2004) Cancer statistics, 2004. CA Cancer J Clin 54:8–29PubMedCrossRef

Kim JH, Yoon SY, Jeong SH et al (2003) Overexpression of Bmi-1 oncoprotein correlates with axillary lymph node metastases in invasive ductal breast cancer. Breast 13:383–388CrossRef

Kim JH, Yoon SY, Kim CN et al (2004) The Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlates with the reduced p16INK4a/p14ARF proteins. Cancer Lett 203:217–224PubMedCrossRef

Leung C, Lingbeek M, Shakhova O et al (2004) Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 428:337–341PubMedCrossRef

Levine SS, King IF, Kingston RE (2005) Division of labor in polycomb group repression. Trends Biochem Sci 29:478–485CrossRef

Liu JH, Song LB, Zhang X et al (2008) Bmi-1 expression predicts prognosis for patients with gastric carcinoma. J Surg Oncol (in press)

Lowe SW, Sherr CJ (2003) Tumor suppression by Ink4a-Arf: progress and puzzles. Curr Opin Genet Dev 13:77–83PubMedCrossRef

Lund AH, van Lohuizen M (2004) Polycomb complexes and silencing mechanisms. Curr Opin Cell Biol 16:239–246PubMedCrossRef

Mihara K, Chowdhury M, Nakaju N et al (2006) Bmi-1 is useful as a novel molecular marker for predicting progression of myelodysplastic syndrome and patient prognosis. Blood 107:305–308PubMedCrossRef

Molofsky AV, He S, Bydon M et al (2005) Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev 19:1432–1437PubMedCrossRef

Nowak K, Kerl K, Fehr D et al (2006) BMI1 is a target gene of E2F-1 and is strongly expressed in primary neuroblastomas. Nucleic Acids Res 34:1745–1754PubMedCrossRef

Park IK, Qian D, Kiel M et al (2003) Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423:302–305PubMedCrossRef

Raaphorst FM (2005) Deregulated expression of Polycomb-group oncogenes in human malignant lymphomas and epithelial tumors. Hum Mol Genet 14:R93–R100PubMedCrossRef

Raaphorst FM, van Kemenade FJ, Blokzijl T et al (2000) Coexpression of BMI-1 and EZH2 polycomb group genes in Reed-Sternberg cells of Hodgkin’s disease. Am J Pathol 157:709–715PubMed

Sandler AB, Johnson DH, Herbst RS (2004) Anti-vascular endothelial growth factor monoclonals in non-small cell lung cancer. Clin Cancer Res 10:4258s–4262sPubMedCrossRef

Satijn DP, Otte AP (1999) Polycomb group protein complexes: do different complexes regulate distinct target genes? Biochem Biophys Acta 1447:1–16PubMed

Schiller JH, Harrington D, Belani CP et al (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92–98PubMedCrossRef

Sewalt RG, van der Vlag J, Gunster MJ et al (1998) Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes. Mol Cell Biol 18:3586–3595PubMed

Silva J, García V, García JM et al (2008) Circulating Bmi-1 mRNA as a possible prognostic factor for advanced breast cancer patients. Breast Cancer Res (in press)

Silvestri GA, Rivera MP (2005) Targeted therapy for the treatment of advanced non-small cell lung cancer: a review of the epidermal growth factor receptor antagonists. Chest 128:3975–3984PubMedCrossRef

Shao Z, Raible F, Mollaaghababa R et al (1999) Stabilization of chromatin structure by PRC1, a Polycomb complex. Cell 98:37–46PubMedCrossRef

Sherr CJ (2001) The INK4a/ARF network in tumour suppression. Nat Rev Mol Cell Biol 10:731–737CrossRef

Song LB, Zeng MS, Liao WT et al (2006) Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells. Cancer Res 15:6225–6232CrossRef

van Kemenade FJ, Raaphorst FM, Blokzijl T et al (2001) Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma. Blood 97:3896–3901PubMedCrossRef

Vonlanthen S, Heighway J, Altermatt HJ et al (2001) The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression. Br J Cancer 84:1372–1376PubMedCrossRef

Wang H, Pan K, Zhang HK et al (2008) Increased polycomb-group oncogene Bmi-1 expression correlates with poor prognosis in hepatocellular carcinoma. J Cancer Res Clin Oncol (in press)

Yu Q, Su B, Liu D et al (2007) Antisense RNA-mediated suppression of Bmi-1 gene expression inhibits the proliferation of lung cancer cell line A549. Oligonucleotides 17:327–335PubMedCrossRef

Titel: Prognostic value of Bmi-1 oncoprotein expression in NSCLC patients: a tissue microarray study
verfasst von: Katerina Vrzalikova
Joseph Skarda
Jiri Ehrmann
Paul G. Murray
Eduard Fridman
Jury Kopolovic
Petra Knizetova
Marian Hajduch
Jiri Klein
Vitezslav Kolek
Lenka Radova
Zdenek Kolar
Publikationsdatum: 01.09.2008
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2008
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-008-0361-y

Neu im Fachgebiet Onkologie

19.04.2024 | EAU 2024 | Kongressbericht | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Prognostic value of Bmi-1 oncoprotein expression in NSCLC patients: a tissue microarray study

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Prostatakarzinom: EU initiiert neues Screeningkonzept

Blasenkarzinom – Biomarker statt Zytologie?

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Adjuvante Brustkrebstherapie: Doppelt hält besser

Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 9/2008

Liposomal honokiol, a promising agent for treatment of cisplatin-resistant human ovarian cancer

Phase II clinical trial of advanced and metastatic gastric cancer based on continuous infusion of 5-fluorouracil combined with epirubicin and oxaliplatin

Expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) inversely correlates with tumor progression in gastric adenomas and carcinomas

Giant cell tumor of bone: treatment and outcome of 214 cases

B7-H1 up-regulated expression in human pancreatic carcinoma tissue associates with tumor progression

Establishment of a nude mouse transplantable model of a human malignant fibrous histiocytoma of the mandible with high metastatic potential to the lung

Neu im Fachgebiet Onkologie

Prostatakarzinom: EU initiiert neues Screeningkonzept

Blasenkarzinom – Biomarker statt Zytologie?

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Adjuvante Brustkrebstherapie: Doppelt hält besser

Update Onkologie