Möllerström et al. BMC Cancer 2010, 10:296 http://www.biomedcentral.com/1471-2407/10/296 Page 7 of 11 Figure 4 Sub-cellular location for samples staining positive for ADIPOR1, ADORA1 and CD46. Brown colour represents staining of the specific protein. Immunohistochemistry staining performed for these proteins on tissue microarrays show staining of ADIPOR1 (A) and ADORA1 (B) as granular staining in the cytoplasm, and expression of CD46 concentrated to the cell membrane (C). antibodies since Kawakubo et al. detected staining pre- dominantly in the nucleus. However, our finding sup- ports the theory that down-regulation of BTG2 contributes to a more malignant behaviour of the cells. BTG2 is therefore a promising prognostic marker in breast cancer. The proteins ADIPOR1, ADORA1 and CD46 did not demonstrate differences in expression between tumours from alive and dead patients. High mRNA levels of ADIPOR1 have earlier been associated with lower risk of breast cancer [35]. Previously, Mirza et al. speculated that increased expression of ADORA1 may contribute to tumour cell growth and decreased apoptosis in breast tumour cells [36]. The intensity of CD46 expression has been negatively correlated with histological grade and type, tumour size, and tumour recurrence but not to overall survival [37], which is supported by the results from this study. These proteins may still be involved in breast cancer progression, although no significant differ- ence was seen in expression between alive and dead Table 4: The effect on the survival status of currently used markers compared to BTG2 expression BTG2 both BTG2 cytoplasm BTG2 membrane A Age HER2 Ki67 B Age HER2 Histological grade 2 Histological grade 3 Hormone receptor status Nodal Status Tumour size Odds Ratio 1.058 0.338 0.699 0.980 3.331 2.441 1.058 2.668 0.954 1.463 0.567 1.673 1.569 Odds Ratio 95%CI 1.031; 1.087 0.336; 0.339 0.697; 0.700 0.977; 0.983 3.248; 3.416 1.202; 4.956 95%CI 1.032; 1.085 2.640; 2.696 0.294; 3.094 0.432; 4.949 0.248; 1.296 0.823; 3.398 0.739; 3.330 P-value < 0.0001* < 0.0001* < 0.0001* < 0.0001* < 0.0001* 0.013* P-value < 0.0001* < 0.0001* 0.938 0.539 0.179 0.154 0.240 C-index C-index 0.711 0.768 0.768 0.768 0.768 0.758 0.696 0.761 0.770 0.770 0.767 0.768 0.765 A Cox-regression multivariate analysis was performed to test the effect on survival status of the markers used in current clinical praxis and the changes in the model predictive power induced by the removal of a single marker. The predictive power of the full new model as measured by the C-index is 0.781 (A). The C-index for the old model is 0.772 (B), and the model with only the statistically significant variables in the old model has a predictive power of 0.739.