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dc.contributor.authorSilva, Priyamal
dc.contributor.authorWest, Catharine M L
dc.contributor.authorSlevin, Nicholas J
dc.contributor.authorValentine, Helen R
dc.contributor.authorRyder, W David J
dc.contributor.authorHampson, Lynne
dc.contributor.authorBibi, Rufzan
dc.contributor.authorSloan, Philip
dc.contributor.authorThakker, Nalin
dc.contributor.authorHomer, Jarrod J
dc.contributor.authorHampson, Ian N
dc.date.accessioned2009-06-22T13:42:49Z
dc.date.available2009-06-22T13:42:49Z
dc.date.issued2007-09-01
dc.identifier.citationTumor expression of major vault protein is an adverse prognostic factor for radiotherapy outcome in oropharyngeal carcinoma. 2007, 69 (1):133-40 Int. J. Radiat. Oncol. Biol. Phys.en
dc.identifier.issn0360-3016
dc.identifier.pmid17459603
dc.identifier.doi10.1016/j.ijrobp.2007.02.025
dc.identifier.urihttp://hdl.handle.net/10541/71161
dc.description.abstractPURPOSE: 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.
dc.language.isoenen
dc.subjectCancer Proteinsen
dc.subjectOropharyngeal Canceren
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshAnalysis of Variance
dc.subject.meshCarcinoma, Squamous Cell
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshMultidrug Resistance-Associated Proteins
dc.subject.meshNeoplasm Proteins
dc.subject.meshOropharyngeal Neoplasms
dc.subject.meshPrognosis
dc.subject.meshRadiation Tolerance
dc.subject.meshRetrospective Studies
dc.subject.meshTreatment Failure
dc.subject.meshVault Ribonucleoprotein Particles
dc.titleTumor expression of major vault protein is an adverse prognostic factor for radiotherapy outcome in oropharyngeal carcinoma.en
dc.typeArticleen
dc.contributor.departmentDepartment of Academic Radiation Oncology, The University of Manchester, Manchester, United Kingdom.en
dc.identifier.journalInternational Journal of Radiation Oncology, Biology, Physicsen
html.description.abstractPURPOSE: 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.


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