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Title: Tumor Epression of Major Vault Protein is an Adverse Prognostic Factor for Radiotherapy Outcome in Oropharyngeal Carcinoma

Journal Article · · International Journal of Radiation Oncology, Biology and Physics
;  [1];  [1]; ;  [2]; ;  [3];  [4];  [2]
  1. Department of Academic Radiation Oncology, University of Manchester, Manchester (United Kingdom)
  2. Manchester Royal Infirmary, Gynaecological Oncology Laboratories, St. Mary's Hospital, Manchester (United Kingdom)
  3. Dental Hospital, Manchester (United Kingdom)
  4. Department of Surgery, Christie Hospital NHS Trust, Manchester (United Kingdom)

Purpose: Vaults are multi-subunit structures that may be involved in nucleo-cytoplasmic transport, with the major vault protein (MVP or lung resistance-related protein [LRP]) being the main component. The MVP gene is located on chromosome 16 close to the multidrug resistance-associated protein and protein kinase c-{beta} genes. The role of MVP in cancer drug resistance has been demonstrated in various cell lines as well as in ovarian carcinomas and acute myeloid leukemia, but nothing is known about its possible role in radiation resistance. Our aim was to examine this in head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Archived biopsy material was obtained for 78 patients with squamous cell carcinoma of the oropharynx who received primary radiotherapy with curative intent. Immunohistochemistry was used to detect MVP expression. Locoregional failure and cancer-specific survival were estimated using cumulative incidence and Cox multivariate analyses. Results: In a univariate and multivariate analysis, MVP expression was strongly associated with both locoregional failure and cancer-specific survival. After adjustment for disease site, stage, grade, anemia, smoking, alcohol, gender, and age, the estimated hazard ratio for high MVP (2/3) compared with low (0/1) was 4.98 (95% confidence interval, 2.17-11.42; p 0.0002) for locoregional failure and 4.28 (95% confidence interval, 1.85-9.95; p = 0.001) for cancer-specific mortality. Conclusion: These data are the first to show that MVP may be a useful prognostic marker associated with radiotherapy resistance in a subgroup of patients with HNSCC.

OSTI ID:
21036208
Journal Information:
International Journal of Radiation Oncology, Biology and Physics, Vol. 69, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2007.02.025; PII: S0360-3016(07)00389-6; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
Country of Publication:
United States
Language:
English