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01-10-2012 | Research

Expression Pattern and Prognostic Significance of IGFBP Isoforms in Anaplastic Astrocytoma

Authors: A. Kulkarni, B. Thota, M. R. Srividya, K. Thennarasu, A. Arivazhagan, V. Santosh, B. A. Chandramouli

Published in: Pathology & Oncology Research | Issue 4/2012

Abstract

The role of insulin- like growth factors and their regulatory proteins (IGFBP isoforms) in gliomas, particularly glioblastoma, has been a subject of active research in recent years. There is paucity of literature on their expression and impact on clinical outcome in anaplastic astrocytomas. To evaluate the expression patterns of IGFBP isoforms in anaplastic astrocytoma and correlate with clinical outcome, a retrospective study of 53 adult patients operated for supratentorial lobar anaplastic astrocytoma was performed. The protein expression of IGFBP isoforms (IGFBP-2, -3, -5 and -7), was studied by immunohistochemistry on all samples. The patients were followed up and outcome was documented. The median age at presentation in the present study was 35 years. The pattern of staining was intra cytoplasmic, homogenous and diffuse for IGFBP-2, -3 and -5 and granular for IGFBP-7. IGFBP-2 expression was significantly low in anaplastic astrocytoma as compared to other isoforms (P < 0.001). IGFBP-3 expression was higher than the other isoforms. However, its’ expression correlated with favorable overall survival and demonstrated a trend towards significance on univariate analysis. The present study is the first of its kind to describe comprehensively the pattern of expression of IGFBP isoforms (IGFBP-2, -3, -5 and -7) in anaplastic astrocytomas. IGFBP-2 and IGFBP-3 expression patterns and correlation to prognosis were distinct in anaplastic astrocytoma patients, contradictory to what has been reported in glioblastoma, thus giving further evidence that anaplastic astrocytomas are molecularly distinct from glioblastoma.

Bondy ML, Scheurer ME, Malmer B, Barnholtz-Sloan JS, Davis FG, Il'yasova D et al (2008) Brain tumor epidemiology: consensus from the brain tumor epidemiology consortium. Cancer 113(7 Suppl):1953–1968PubMedCrossRef

Central Brain Tumor Registry of the United States (CBTRUS) (2008) Statistical Report: Primary Brain Tumors in the United States, 2000–2004. Hinsdale, Ill: Central Brain Tumor Registry of the United States

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A et al (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109PubMedCrossRef

Nomiya T, Nemoto K, Kumabe T, Takai Y, Yamada S (2007) Prognostic significance of surgery and radiation therapy in cases of anaplastic astrocytoma: retrospective analysis of 170 cases. J Neurosurg 106(4):575–581PubMedCrossRef

Prados MD, Seiferheld W, Sandler HM, Buckner JC, Phillips T, Schultz C et al (2004) Phase III randomized study of radiotherapy plus procarbazine, lomustine, and vincristine with or without BUdR for treatment of anaplastic astrocytoma: final report of RTOG 9404. Int J Radiat Oncol Biol Phys 58(4):1147–1152PubMedCrossRef

Smith JS, Tachibana I, Passe SM et al (2001) PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst 93:1246–1256PubMedCrossRef

Daumas-Duport C, Scheithauer BW, O’Fallon JR, Kelly P (1988) Grading of astrocytomas: a simple and reproducible method. Cancer 62:2152–2165PubMedCrossRef

Prados MD, Gutin PH, Phillips TL, Wara WM, Larson DA, Sneed PK et al (1992) Highly anaplastic astrocytoma: a review of 357 patients treated between 1977 and 1989. Int J Radiat Oncol Biol Phys 23:3–8PubMedCrossRef

Cunningham JM, Kimmel DW, Scheithauer BW, O’Fallon JR, Novotny PJ, Jenkins RB (1997) Analysis of proliferation markers and p53 expression in gliomas of astrocytic origin: relationships and prognostic value. J Neurosurg 86:121–130PubMedCrossRef

10.

Hai Yan D, Parsons W, Jin G, Roger McLendon B et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360(8):765–773PubMedCrossRef

11.

Wang H, Fuller GN, Zhang W (2004) Insulin-like growth factors and insulin-like growth factors binding proteins in CNS tumors. In: Zhang W, Fuller GN (eds) Genomic and molecular neuro-oncology. Jones and Bartlett Publishers, Sudbury, pp 119–130

12.

Trojan J, Cloix JF, Ardourel MY, Chatel M, Anthony DD (2007) Insulin-like growth factor type I biology and targeting in malignant gliomas. Neuroscience 145:795–811PubMedCrossRef

13.

Fuller GN, Rhee CH, Hess KR, Caskey LS, Wang R, Bruner JM et al (1999) Reactivation of insulin-like growth factor binding protein 2 expression in glioblastoma multiforme: a revelation by parallel gene expression profiling. Cancer Res 59(17):4228–4232PubMed

14.

Fukushima T, Kataoka H (2007) Roles of insulin-like growth factor binding protein-2 (IGFBP-2) in glioblastoma. Anticancer Res 27(6A):3685–3692PubMed

15.

Santosh V, Arivazhagan A, Sreekanthareddy P, Srinivasan H, Thota B, Srividya MR et al (2010) Grade-specific expression of insulin-like growth factor–binding proteins-2, -3, and −5 in astrocytomas: IGFBP-3 emerges as a strong predictor of survival in patients with newly diagnosed glioblastoma. Cancer Epidemiol Biomarkers Prev 19(6):1399–1408PubMedCrossRef

16.

Moore LM, Holmes KM, Smith SM, Wu Y, Tchougounova E, Uhrbom L et al (2009) IGFBP2 is a candidate biomarker for Ink4a-Arf status and a therapeutic target for high-grade gliomas. Proc Natl Acad Sci U S A 106(39):16675–16679PubMedCrossRef

17.

Wang H, Shen W, Huang H, Hu L, Ramdas L, Zhou YH et al (2003) Insulin-like growth factor binding protein 2 enhances glioblastoma invasion by activating invasion-enhancing genes. Cancer Res 63(15):4315–4321PubMed

18.

McDonald KL, O'Sullivan MG, Parkinson JF, Shaw JM, Payne CA, Brewer JM et al (2007) IQGAP1 and IGFBP2: valuable biomarkers for determining prognosis in glioma patients. J Neuropathol Exp Neurol 66(5):405–417PubMedCrossRef

19.

Reddy SP, Britto R, Vinnakota K, Aparna H, Sreepathi HK, Thota B et al (2008) Novel glioblastoma markers with diagnostic and prognostic value identified through transcriptome analysis. Clin Cancer Res 14(10):2978–2987PubMedCrossRef

20.

Lin Y, Jiang T, Zhou K, Xu L, Chen B, Li G et al (2009) Plasma IGFBP-2 levels predict clinical outcomes of patients with high-grade gliomas. Neuro Oncol 11(5):468–476PubMedCrossRef

21.

Wang H, Zhang W, Fuller GN (2006) Overexpression of IGFBP5, but not IGFBP3, correlates with the histologic grade of human diffuse glioma: a tissue microarray and immunohistochemical study. Technol Cancer Res Treat 5(3):195–199PubMed

22.

O'Han MK, Baxter RC, Schedlich LJ (2009) Effects of endogenous insulin-like growth factor binding protein-3 on cell cycle regulation in breast cancer cells. Growth Factors 27(6):394–408PubMedCrossRef

23.

Vestey SB, Perks CM, Sen C, Calder CJ, Holly JM, Winters ZE (2005) Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome. Breast Cancer Res 7(1):R119–R129PubMedCrossRef

24.

Butt AJ, Martin JL, Dickson KA, McDougall F, Firth SM, Baxter RC (2004) Insulin-like growth factor binding protein-3 expression is associated with growth stimulation of T47D human breast cancer cells: the role of altered epidermal growth factor signaling. J Clin Endocrinol Metab 89(4):1950–1956PubMedCrossRef

25.

Kim HS, Lee WJ, Lee SW, Chae HW, Kim DH, Oh Y (2010) Insulin-like growth factor binding protein-3 induces G1 cell cycle arrest with inhibition of cyclin-dependent kinase 2 and 4 in MCF-7 human breast cancer cells. Horm Metab Res 42(3):165–172PubMedCrossRef

26.

Dupart JJ, Trent JC, Lee HY, Hess KR, Godwin AK, Taguchi T et al (2009) Insulin-like growth factor binding protein-3 has dual effects on gastrointestinal stromal tumor cell viability and sensitivity to the anti-tumor effects of imatinib mesylate in vitro. Mol Cancer 8:99PubMedCrossRef

27.

Chang MH, Lee J, Han J, Park YH, Ahn JS, Park K et al (2009) Prognostic role of insulin-like growth factor receptor-1 expression in small cell lung cancer. APMIS 117(12):861–869PubMedCrossRef

28.

Sztefko K, Hodorowicz-Zaniewska D, Popiela T, Richter P (2009) IGF-I, IGF-II, IGFBP2, IGFBP3 and acid-labile subunit (ALS) in colorectal cancer patients before surgery and during 1 year follow up in relation to age. Adv Med Sci 54(1):51–58PubMedCrossRef

29.

Miyake H, Pollak M, Gleave ME (2000) Castration-induced up-regulation of insulin-like growth factor binding protein-5 potentiates insulin-like growth factor-I activity and accelerates progression to androgen independence in prostate cancer models. Cancer Res 60(11):3058–3064PubMed

30.

Hou XJ, Zhang YZ, Liu X, Meng LH, Qiao YB (2009) Expressions of IGFBP-5, cFLIP in cervical intraepithelial neoplasia, cervical carcinoma and their clinical significances: a molecular pathology. J Exp Clin Cancer Res 28:70PubMedCrossRef

Title: Expression Pattern and Prognostic Significance of IGFBP Isoforms in Anaplastic Astrocytoma
Authors: A. Kulkarni
B. Thota
M. R. Srividya
K. Thennarasu
A. Arivazhagan
V. Santosh
B. A. Chandramouli
Publication date: 01-10-2012
Publisher: Springer Netherlands
Published in: Pathology & Oncology Research / Issue 4/2012
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-012-9526-8

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