Volume 148, Issue 1, Pages 174-180 (January 2018) An NRG Oncology/GOG study of molecular classification for risk prediction in endometrioid endometrial cancer  Casey M. Cosgrove, David L. Tritchler, David E. Cohn, David G. Mutch, Craig M. Rush, Heather A. Lankes, William T. Creasman, David S. Miller, Nilsa C. Ramirez, Melissa A. Geller, Matthew A. Powell, Floor J. Backes, Lisa M. Landrum, Cynthia Timmers, Adrian A. Suarez, Richard J. Zaino, Michael L. Pearl, Paul A. DiSilvestro, Shashikant B. Lele, Paul J. Goodfellow  Gynecologic Oncology  Volume 148, Issue 1, Pages 174-180 (January 2018) DOI: 10.1016/j.ygyno.2017.10.037 Copyright © 2017 Elsevier Inc. Terms and Conditions

Fig. 1 Molecular classes and association with clinicopathologic and demographic variables for 982 endometrioid endometrial cancers. Frequency distribution of the four molecular classes. (A) Overlap of POLE mutations with MMR deficient and copy number altered molecular classes. The POLE classification was restricted to those tumors with normal DNA mismatch repair with no evidence of copy number alteration/LOH (B) and patterns seen across the four classes for significantly associated variables. Pearson's Chi-squared tests P values (C). Gynecologic Oncology 2018 148, 174-180DOI: (10.1016/j.ygyno.2017.10.037) Copyright © 2017 Elsevier Inc. Terms and Conditions

Fig. 2 Survival analysis for the four molecular classes of endometrioid endometrial cancer. Shown are the Kaplan-Meier plots of patient (A) progression-free survival, (B) endometrial cancer-specific, and (C) overall survival by molecular group. Nominal P values are presented with no adjustment for multiple testing. HR=hazard ratio. Gynecologic Oncology 2018 148, 174-180DOI: (10.1016/j.ygyno.2017.10.037) Copyright © 2017 Elsevier Inc. Terms and Conditions

Fig. S1 Hierarchical classification of EEC based on molecular findings. All tumors were characterized for MMR defects (IHC, MSI, and MLH1 methylation), LOH and POLE mutations. Those subjects not informative for markers used to assess LOH (N=51) could not be classified. Gynecologic Oncology 2018 148, 174-180DOI: (10.1016/j.ygyno.2017.10.037) Copyright © 2017 Elsevier Inc. Terms and Conditions

Fig. S2 Patterns of LOH across the 84 tumors classified as copy number altered (CNA). In addition to the eight tumors with LOH at all three loci (left side), nine cases had loss at two loci and were not informative for the third. Six cases had loss at one locus and were not informative at the other two, for a total of 23 cases for which loss of all three loci is possible. Thirty-one tumors on the other hand were informative for all three markers and showed LOH at a single site. Gynecologic Oncology 2018 148, 174-180DOI: (10.1016/j.ygyno.2017.10.037) Copyright © 2017 Elsevier Inc. Terms and Conditions

Fig. S3 Relationship between TCGA genome-wide copy alteration estimates and copy number altered molecular class based on GISTIC findings for the D17S250, D5S346 and D2S123 region. The four molecular classes determined using the three-marker LOH, MMR and POLE status are indicated with colored bars. The putative genome-wide copy number alterations based on GISTIC 2.0 are presented as fraction genome altered (FGA). Black bars indicate the 16 cases classified as copy number altered based on GISTIC findings for the three regions of interest. Figure adapted from cBioPortal [36,37]. Gynecologic Oncology 2018 148, 174-180DOI: (10.1016/j.ygyno.2017.10.037) Copyright © 2017 Elsevier Inc. Terms and Conditions

Fig. S4 Representative TP53 IHC staining for copy number altered tumors. (A) Sample G471T harboring a missense mutation and positive (mutant) p53 staining. (B) Sample G472T with no mutation and normal (absent) staining. (C) Sample G286T with loss-of-function mutation(s) and normal (absent) staining. (D) Tonsil tissue used as positive control for staining. p53 detected using clone DO-7 monoclonal antibody. 10× magnification. Gynecologic Oncology 2018 148, 174-180DOI: (10.1016/j.ygyno.2017.10.037) Copyright © 2017 Elsevier Inc. Terms and Conditions