Top

Radiation Oncology

Published in:

Open Access 01-12-2012 | Research

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

Authors: Luis Alberto Henríquez-Hernández, Mercedes Moreno, Agustín Rey, Marta Lloret, Pedro C Lara

Published in: Radiation Oncology | Issue 1/2012

Abstract

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.

Available only for authorised users

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. 10.1083/jcb.146.5.917PubMedCentralCrossRefPubMed

Mossink MH, van Zon A, Scheper RJ, Sonneveld P, Wiemer EA: Vaults: a ribonucleoprotein particle involved in drug resistance? Oncogene 2003, 22: 7458-7467. 10.1038/sj.onc.1206947CrossRefPubMed

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. 10.2174/138945006778019345CrossRefPubMed

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.PubMed

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. 10.1158/0008-5472.CAN-05-0423CrossRefPubMed

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.PubMed

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. 10.1158/0008-5472.CAN-05-0770CrossRefPubMed

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. 10.1016/j.ijrobp.2007.02.025CrossRefPubMed

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.PubMed

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. 10.1074/jbc.M209809200CrossRefPubMed

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. 10.1016/j.semradonc.2005.08.008CrossRefPubMed

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. 10.1016/j.ygyno.2007.04.004CrossRefPubMed

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. 10.1016/j.oraloncology.2011.05.005CrossRefPubMed

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. 10.1016/j.ygyno.2008.04.034CrossRefPubMed

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. 10.1016/j.ygyno.2011.05.037CrossRefPubMed

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. 10.1016/j.ijrobp.2008.11.013CrossRefPubMed

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. 10.1038/sj.onc.1210037CrossRefPubMed

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.PubMed

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. 10.1073/pnas.98.4.1676PubMedCentralCrossRefPubMed

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. 10.1210/en.2004-0613CrossRefPubMed

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. 10.1186/1748-717X-4-29PubMedCentralCrossRefPubMed

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. 10.1016/j.radonc.2008.07.018CrossRefPubMed

23.

Lara PC, Pruschy M, Zimmermann M, Henriquez-Hernandez LA: MVP and vaults: a role in the radiation response. Radiat Oncol 2011, 6: 148. 10.1186/1748-717X-6-148PubMedCentralCrossRefPubMed

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. 10.1007/s12178-011-9105-8PubMedCentralCrossRefPubMed

Title: MVP expression in the prediction of clinical outcome of locally advanced oral squamous cell carcinoma patients treated with radiotherapy
Authors: Luis Alberto Henríquez-Hernández
Mercedes Moreno
Agustín Rey
Marta Lloret
Pedro C Lara
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Radiation Oncology / Issue 1/2012
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/1748-717X-7-147

At a glance: The STEP trials

Springer Medicine

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

Abstract

Objective

Subjects and Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Objective

Subjects and Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2012

Computed tomography-guided permanent brachytherapy for locoregional recurrent gastric cancer

Intraoperative radiation therapy with the photon radiosurgery system in locally advanced and recurrent rectal cancer: retrospective review of the Cleveland clinic experience

Use of combined maximum and minimum intensity projections to determine internal target volume in 4-dimensional CT scans for hepatic malignancies

A technique for pediatric total skin electron irradiation

Total skin electron beam therapy as palliative treatment for cutaneous manifestations of advanced, therapy-refractory cutaneous lymphoma and leukemia

Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma