P<0.001 P=0.001 P<0.001 Ep-CAM expression ≤ 75% percentile (n=147) Ep-CAM expression > 75% percentile (n=47) Ep-CAM expression ≤ 75% percentile (n=147)

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P<0.001 P=0.001 P<0.001 Ep-CAM expression ≤ 75% percentile (n=147) Ep-CAM expression > 75% percentile (n=47) Ep-CAM expression ≤ 75% percentile (n=147) Ep-CAM expression > 75% percentile (n=47) Ep-CAM expression ≤ 75% percentile (n=147) Ep-CAM expression > 75% percentile (n=47) A B C Supplemental Fig. 1: High Ep-CAM RNA levels are associated with shorter disease free survival time (A), shorter metastasis free survival time (B) and shorter overall survival time (C). Levels of Ep-CAM RNA expression were dichotomized at the 75% percentile (corresponding data to Fig. 2 where data were dichotomized at the median).

P=0.119 P=0.182 P=0.031 Ep-CAM status negative (n=144) Ep-CAM status negative (n=144) Ep-CAM status negative (n=144) Ep-CAM status Positive (n=49) Ep-CAM status Positive (n=49) Ep-CAM status Positive (n=49) Supplemental Fig. 2: Immunohistochemically determined Ep-CAM status showed only trends towards shorter disease free survival and metastasis free survival time. A C B

Supplemental Fig. 3: Estrogen receptor, her-2 and progesterone receptor RNA expression show bimodal frequency distributions in 782 patients with node-negative breast cancer (combined cohort). Similar results were obtained for the individual subcohorts (Supplemental Fig. 4). The arrows indicate positions of the cutpoints for dichotomization. Log2 transformed gene array data were used.

Supplemental Fig. 4: Estrogen receptor, her-2 and progesterone receptor RNA expression show bimodal frequency distributions also in the individual subcohorts, the Transbig cohort (A), the Mainz cohort (B) and the Rotterdam cohort (C). Data correspond to Supplemental Fig. 3. A. Transbig cohort (n=302)

B. Mainz cohort (n=194) Supplemental Fig. 4

C. Rotterdam cohort (n=286) Supplemental Fig. 4

Supplemental Fig. 5: Ep-CAM RNA expression correlates with the proliferation metagene which has recently been established by Schmidt et al. (2008). R=0.425 P<0.001 N=782

Supplemental Fig. 6: Ep-CAM RNA levels in different intrinsic subtypes of node negative breast cancer. Ep-CAM expression in normal-like carcinomas (n=21) is lower compared to basal-like (P<0.001; n=21), ERBB2-like (P<0.001; n=25), and luminal B (P<0.001; n=69) subtypes. The difference between normal-like and luminal A (n=63) subtypes did not amount to statistical significance (P=0.08).