The role of lung resistance protein in radiation treated head and neck carcinoma

Objectives. Vault proteins are ribonucleotide proteins composed largely of a single large protein termed major vault protein. (MVP) The (MVP) LRP gene is located on chromosome 16 close to the genes coding for multidrug resistance-associated protein and protein kinase c-β. The role of MVP (LRP) in cancer drug resistance has been demonstrated in various cell lines as well as in ovarian carcinomas and acute myeloid leukaemia, however little is known about its possible role in radiation resistance.1,2 Our aim was to examine this in head and neck squamous carcinoma (HNSCC). Method. One hundred and thirty three patients with proven squamous cell carcinoma of the oropharynx were recruited into the study, looking at two subsites of posterior tongue and tonsil. These patients received primary radiotherapy with curative intent. Archived biopsy material was obtained for 78 patients. Immunohistochemistry was used to detect LRP expression. Locoregional failure and cancer specific survival were estimated using Kaplan Meier method. Results. On analysis of the whole group together LRP expression was strongly associated with locoregional failure (P < 0.0001) however, on subgroup analysis there was an obvious difference between the two sites, with increased LRP expression being associated with poor prognosis in the tongue group (P < 0.0001), but not the tonsil group. (P = 0.14). Conclusion. This is the first reported study of LRP as a prognostic marker in radiotherapy treated HNSCC suggesting it may play an important role not just in cancer drug resistance but also in radiation resistance. Of added interest is the difference in prognostic significance between the two subsites. References 1 Scheffer G.L., Wijngaard P.L., Flens M.J., et al. (1995) The drug resistance-related protein LRP is the human major vault protein. Nature Med.1, 578–582 2 Kozlov G., Vavelyuk O., Ovidiu M., et al. (2005) Solution structure of a two-repeat fragment of major vault protein. J. Mol. Biol.7