MVP expression in the prediction of clinical outcome of locally advanced oral squamous cell carcinoma patients treated with radiotherapy

Radiation Oncology

Pedro C Lara¹  Marta Lloret¹  Agustín Rey³  Mercedes Moreno²  Luis Alberto Henríquez-Hernández¹ 

[1] Clinical Sciences Department, Universidad de Las Palmas de Gran Canaria;Department of Maxillofacial Surgery, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain;Department of Pathology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain

关键词: Predictive factor;    Radiotherapy;    Oral carcinoma;    IGF-1R;    MVP;   

Others  :  1155366
DOI  :  10.1186/1748-717X-7-147

 received in 2012-04-11, accepted in 2012-08-13,  发布年份 2012

【 摘 要 】

Objective

To explore the role of Major Vault Protein (MVP) in oral cavity squamous cell carcinoma patients.

Subjects and Methods

131 consecutive patients suffering from oral cavity squamous cell carcinoma were included in the study. In the whole series, the mean follow-up for survivors was 123.11 ± 40.36 months. Patients in tumour stages I and II were referred to surgery; patients in stage III-IV to postoperative radiotherapy (mean dose = 62.13 ± 7.74 Gy in 1.8–2 Gy/fraction). MVP expression was studied by immunohistochemistry in paraffin-embedded tumour tissue.

Results

MVP expression was positive in 112 patients (85.5%) and no relation was found with clinic pathological variables. MVP overexpression (those tumours with moderate or strong expression of the protein) was related to insulin-like growth factor receptor-1 (IGF-1R) expression (P = 0.014). Tumour stage of the disease was the most important prognostic factor related to survival. Tumours overexpressing MVP and IGF-1R were strongly related to poor disease-free survival (P = 0.008, Exp(B) = 2.730, CI95% (1.302-5.724)) and cause-specific survival (P = 0.014, Exp(B) = 2.570, CI95% (1.215-5.437)) in patients achieving tumour stages III-IV, in multivariate analysis.

Conclusions

MVP and IGF-1R expression were related in oral squamous cell carcinoma and conferred reduced long-term survival in patients suffering from advanced stages of the disease.

【 授权许可】

   
2012 Henriquez-Hernandez et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Kickhoefer VA, Siva AC, Kedersha NL, Inman EM, Ruland C, Streuli M, Rome LH: The 193-kD vault protein, VPARP, is a novel poly(ADP-ribose) polymerase. J Cell Biol 1999, 146:917-928.
• [2]Mossink MH, van Zon A, Scheper RJ, Sonneveld P, Wiemer EA: Vaults: a ribonucleoprotein particle involved in drug resistance? Oncogene 2003, 22:7458-7467.
• [3]Steiner E, Holzmann K, Elbling L, Micksche M, Berger W: Cellular functions of vaults and their involvement in multidrug resistance. Curr Drug Targets 2006, 7:923-934.
• [4]Fichtner I, Paal K, Borgmann A, Badiali L, Wurm R, Henze G: Chemo- and radiation sensitivity of xenografted acute lymphoblastic leukemias–correlation to the expression of multidrug resistance proteins. Anticancer Res 2003, 23:2657-2664.
• [5]Yi C, Li S, Chen X, Wiemer EA, Wang J, Wei N, Deng XW: Major vault protein, in concert with constitutively photomorphogenic 1, negatively regulates c-Jun-mediated activator protein 1 transcription in mammalian cells. Cancer Res 2005, 65:5835-5840.
• [6]Shimamoto Y, Sumizawa T, Haraguchi M, Gotanda T, Jueng HC, Furukawa T, Sakata R, Akiyama S: Direct activation of the human major vault protein gene by DNA-damaging agents. Oncol Rep 2006, 15:645-652.
• [7]Raval-Fernandes S, Kickhoefer VA, Kitchen C, Rome LH: Increased susceptibility of vault poly(ADP-ribose) polymerase-deficient mice to carcinogen-induced tumorigenesis. Cancer Res 2005, 65:8846-8852.
• [8]Silva P, West CM, Slevin N, Valentine H, Ryder WD, Hampson L, Bibi R, Sloan P, Thakker N, Homer J, Hampson I: Tumor expression of major vault protein is an adverse prognostic factor for radiotherapy outcome in oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys 2007, 69:133-140.
• [9]Turner BC, Haffty BG, Narayanan L, Yuan J, Havre PA, Gumbs AA, Kaplan L, Burgaud JL, Carter D, Baserga R, Glazer PM: Insulin-like growth factor-I receptor overexpression mediates cellular radioresistance and local breast cancer recurrence after lumpectomy and radiation. Cancer Res 1997, 57:3079-3083.
• [10]Yu D, Watanabe H, Shibuya H, Miura M: Redundancy of radioresistant signaling pathways originating from insulin-like growth factor I receptor. J Biol Chem 2003, 278:6702-6709.
• [11]Chinnaiyan P, Allen GW, Harari PM: Radiation and new molecular agents, part II: targeting HDAC, HSP90, IGF-1R, PI3K, and Ras. Semin Radiat Oncol 2006, 16:59-64.
• [12]Lloret M, Lara PC, Bordon E, Pinar B, Rey A, Falcon O, Molano F, Hernandez MA: IGF-1R expression in localized cervical carcinoma patients treated by radiochemotherapy. Gynecol Oncol 2007, 106:8-11.
• [13]Lara PC, Bordon E, Rey A, Moreno M, Lloret M, Henriquez-Hernandez LA: IGF-1R expression predicts clinical outcome in patients with locally advanced oral squamous cell carcinoma. Oral Oncol 2011, 47:615-619.
• [14]Lloret M, Lara PC, Bordon E, Rey A, Falcon O, Apolinario RM, Clavo B, Ruiz A: MVP expression is related to IGF1-R in cervical carcinoma patients treated by radiochemotherapy. Gynecol Oncol 2008, 110:304-307.
• [15]Henriquez-Hernandez LA, Lloret M, Pinar B, Bordon E, Rey A, Lubrano A, Lara PC: BCL-2, in combination with MVP and IGF-1R expression, improves prediction of clinical outcome in complete response cervical carcinoma patients treated by radiochemotherapy. Gynecol Oncol 2011, 122:585-589.
• [16]Lloret M, Lara PC, Bordon E, Fontes F, Rey A, Pinar B, Falcon O: Major vault protein may affect nonhomologous end-joining repair and apoptosis through Ku70/80 and bax downregulation in cervical carcinoma tumors. Int J Radiat Oncol Biol Phys 2009, 73:976-979.
• [17]Cosaceanu D, Budiu RA, Carapancea M, Castro J, Lewensohn R, Dricu A: Ionizing radiation activates IGF-1R triggering a cytoprotective signaling by interfering with Ku-DNA binding and by modulating Ku86 expression via a p38 kinase-dependent mechanism. Oncogene 2007, 26:2423-2434.
• [18]Rocha RL, Hilsenbeck SG, Jackson JG, VanDenBerg CL, Weng C, Lee AV, Yee D: Insulin-like growth factor binding protein-3 and insulin receptor substrate-1 in breast cancer: correlation with clinical parameters and disease-free survival. Clin Cancer Res 1997, 3:103-109.
• [19]Peretz S, Jensen R, Baserga R, Glazer PM: ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response. Proc Natl Acad Sci U S A 2001, 98:1676-1681.
• [20]Shahrabani-Gargir L, Pandita TK, Werner H: Ataxia-telangiectasia mutated gene controls insulin-like growth factor I receptor gene expression in a deoxyribonucleic acid damage response pathway via mechanisms involving zinc-finger transcription factors Sp1 and WT1. Endocrinology 2004, 145:5679-5687.
• [21]Lara PC, Lloret M, Clavo B, Apolinario RM, Henriquez-Hernandez LA, Bordon E, Fontes F, Rey A: Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression. Radiat Oncol 2009, 4:29. BioMed Central Full Text
• [22]Lara PC, Lloret M, Clavo B, Apolinario RM, Bordon E, Rey A, Falcon O, Alonso AR, Belka C: Hypoxia downregulates Ku70/80 expression in cervical carcinoma tumors. Radiother Oncol 2008, 89:222-226.
• [23]Lara PC, Pruschy M, Zimmermann M, Henriquez-Hernandez LA: MVP and vaults: a role in the radiation response. Radiat Oncol 2011, 6:148. BioMed Central Full Text
• [24]Valenciano A, Henriquez-Hernandez LA, Moreno M, Lloret M, Lara PC: Role of IGF-1 Receptor in Radiation Response. Transl Oncol 2012, 5:1-9.