In our study, survivin is significantly related to the nodal status, which may suggest that survivin plays the key role in lymph node metastasis, as in the previous report [25]; however, survivin was not a significant prognostic factor in the present study. It is difficult to estimate the prognostic value of survivin because the

power of this study was low due to the learn more limited sample size; therefore, we considered the combination of biomarkers to be more powerful to show the prognostic value of survivin and p53 AIP1. The rationale was as follows, since p53 leads to the repression of survivin expression, and apoptotic cells induced by p53 caused resistance to apoptosis when survivin was overexpressed [21], p53 AIP1 might

have an inverse effect against survivin in the same manner as p53. Furthermore, as the relationship between survivin and p53AIP1 has not been investigated, we hypothesized that the combination analysis of survivin with p53AIP1 can be a powerful tool for risk stratification. Erastin molecular weight The combination of negative p53AIP1 and positive survivin showed the worst prognosis, leading to the speculation that these two genes act in an opposite manner and are critical for tumor progression. Multivariate analysis showed that the combination of these genes was an independent predictor of survival. Furthermore, p53AIP1 and survivin expressions in non-small cell lung cancer cells before chemotherapy may contribute as independent predictors of the effect of chemotherapy, such as DNA-damaging agents. In conclusion, although the sample size was small, our study demonstrated that the combination of survivin with p53AIP1 gene expression in non-small cell lung cancer is a possible independent prognostic factor. Further investigation of these combinations might show the prognostic significance of these genes in non-small cell lung this website cancer. Acknowledgements

This study was supported by a grant for National Hospital Clinical Research from the Ministry of Health, Labour and Welfare of Japan. We are grateful to Dr Yuji Onodera, BML Inc., for technical support and Ms. Yoko Miyanari, Department of Surgery II, Oita University Faculty of Medicine. References 1. Harris CC, Hollstein M: Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 1993, 329: 1318–1327.CrossRefPubMed 2. Mitsudomi T, Hamajima N, Ogawa M, Takahashi T: Prognostic significance of p53 alterations in patients with non-small cell lung cancer: a meta-analysis. Clin Cancer Res 2000, 6: 4055–4063.PubMed 3. Steele RJ, Thompson AM, Hall PA, Lane DP: The p53 tumour suppressor gene. Br J Surg 1998, 85: 1460–1467.CrossRefPubMed 4. Pfeifer GP, Denissenko MF, Olivier M, Tretyakova N, Hecht SS, Hainaut P: Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene 2002, 21: 7435–7451.CrossRefPubMed 5. Vogelstein B, Lane D, Levine AJ: Surfing the p53 network. Nature 2000, 408: 307–310.CrossRefPubMed 6.