Fig. 1.

Tumour hypoxia as assessed by high expression of HIF-1α and CA-9 affects metformin response in vivo. Increased tumour hypoxia is positively correlated with grade using a HIF-1α (r = 0.42, p = 0.07) and b CA-9 (r = 0.46, p = 0.03) IHC expression (n = 40 women). Numbers of tumours in each grade are: 2 atypical hyperplasia (AEH), 15 grade 1, 19 grade 2 and 4 grade 3. Change in Ki-67 (i.e. response to metformin) was correlated with baseline c HIF-1α and d CA-9. The figures illustrate the change in Ki-67 in endometrial tumour biopsies taken pre- and post-metformin treatment in 28 patients. Response to metformin was lower in hypoxic tumours as assessed by HIF-1α [mean adjusted difference 2.5% (95% CI 0.4, 4.6%), p = 0.018] and approached statistical significance with CA-9 [mean adjusted difference 10.9% (95% CI -2.0, 23.7%, p = 0.09) using an analysis of covariance