Supplementary Figure Legends

Table 1. Univariate analysis of phosphoprotein markers used in the study. Cutpoints for survival were selected using Xtile (see materials and methods) and minimum p-values corrected to minimise Type I error. Only variables with p<0.05 after Monte-Carlo simulation were considered significant.

Figure 1. Phosphoprotein expression of the five genetic pathway markers between histological subtypes in cohort 1 (p-values; Kruskal-Wallis test).

Figure 2. Unsupervised clustering of the five genetic pathway markers in cohort 2 reveals two main clusters (A), which do not differ with respect to prognosis. While patients with cluster 1 tumours have a worse outcome when treated with taxanes (log-rank p=0.031), this is not significant in multivariate analysis.

Figure 3. Unsupervised cluster analysis of cohort 1 tumours shows two main clusters with similar profiles of expression as in cohort 2.

Figure 4. Schematic of the pathways analysed in this study.

Figure 5. Expression of phosphoprotein markers according to histological subtype demostrates heterogeneity. (cohort 2).

Figure 6. K-means clustering of phosphoprotein data (cohort 1 shown here) produces 4 distinct phosphoprotein clusters (A) with different profiles of pathway alteration (B). (C) Overall survival according to phosphoprotein cluster show no differences in prognosis according to phosphoprotein cluster in this cohort of patients.

Cohort 1 Cohort 2

Target Minimum p-value

(corrected)

Monte-Carlo p-value HR (95% CI) Minimum p-value (corrected)

Monte-Carlo p-value

HR (95% CI)

pAKT (Ser 473) 0.220 0.680 N/A 0.382 0.480 N/A

pERK (Thr202/204) 0.082 0.550 N/A 0.660 0.680 N/A

pER (Ser118) 0.575 0.800 N/A 0.138 0.270 N/A

pCatenin (Ser33/37/41)

0.585 0.820 N/A 0.150 0.350 N/A

pSTAT3 (Ser727) 0.481 0.850 N/A 0.499 0.760 N/A

pNFB (Ser529) 0.316 0.710 N/A 0.595 0.730 N/A

pRB (Ser807/811) 0.341 0.740 N/A 0.610 0.620 N/A

pH2AX (Ser139) 0.328 0.690 N/A 0.030 0.050 1.47 (1.14,1.88)

pBRCA1 (Ser1524) 0.005 0.270 N/A 0.021 0.040 1.47 (1.17, 1.86)

p-p53 (Ser15) 0.369 0.640 N/A 0.550 0.580 N/A

Ki67 0.009 0.370 N/A 0.510 0.390 N/A

pHH3 0.035 0.390 N/A 0.050 0.040 1.47 (1.17, 1.80)

Caspase 3 0.132 0.550 N/A 0.614 0.570 N/A

Supplementary Table 1

Supplementary Figure 1

p=0.133 p=0.003 p=0.001

p=0.145 p=0.157

Supplementary Figure 2

Cluster 1 Cluster 2

A

B

p=0.436 p=0.482 p=0.031

Cluster 1 Cluster 2

Supplementary Figure 3

JAKJAK

TNFRTNFR

RTKRTKCadherinCadherin

RAS

RAF

MEK

ERK

PI3K

PIP2PIP3

AKT

STAT3

-Catenin

ER

NFB p50/52

p65/RelA

IKKIKK

IKK

p53

BRCA1

Histone H2A.X

Supplementary Figure 4

P

P

P

P

P

P

P

P

P

Supplementary Figure 5

Serous EndometrioidMixed CCMuc Other

Supplementary Figure 6

Cluster 1Cluster 2Cluster 3Cluster 4

A

B C