Endometrial cancer molecular profiling in a Caribbean-Black patient population (404)

Abstract

Objectives: To characterize the molecular profiles of endometrial cancer (EC) and correlate with clinical outcomes in a Caribbean- Black patient population. Methods: A multi-center retrospective analysis of Caribbean-Black patients with surgically staged EC from 2015-2021 was conducted. All patients underwent comprehensive surgical staging and/or tumor debulking and molecular tumor profiling performed on pathologic specimens via next-generation sequencing (NGS). Tumors were classified based on TCGA/ProMisE classification: MMR deficient (MMR-d/ MSI-H), p53 abnormal (p53abn), p53 wild type (p53wt), and POLE mutated (POLEmut). Differences in the frequencies of histologic subtypes, stage distribution, and adjuvant therapy were compared using Pearson’s Chi-square test. Progression-free survival (PFS) and overall survival (OS) rates were calculated between p53abn versus other mutational profiles (p53wt and MMR-d/MSI-H) using Kaplan- Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. Results: Of the 119 patients meeting inclusion criteria, the final analysis included 76 patients with complete follow-up data. Tumors were classified as MMR-d/MSI-H (n=11, 14.5%), p53abn (n=43, 56.6%), p53wt (n=21, 27.6%), and POLEmut (n=1, 1.3%). The median age at diagnosis was 64 years (range: 26-82). Histology included 44.0% endometrioid, 47.5% uterine serous (USC), 14.5% carcinosarcoma, and 8.5% clear cell adenocarcinomas. There was no significant difference in the stage distribution between different mutation profiles (p=0.725). USC tumors were associated with p53abn, and endometrioid tumors were associated with MMR-d/MSI-H (p<0.01). All carcinosarcoma patients were p53abn. Patients with p53abn tumors were significantly more likely to receive chemotherapy alone or in combination with radiotherapy versus all other cohorts (p<0.01). One patient with stage IA endometrioid tumor demonstrated POLEmut; this patient remains recurrence-free without adjuvant therapy and was excluded from survival analyses. When compared to all other mutational profiles, p53abn tumors trended towards poorer PFS (29 vs 22 months, respectively; p=0.209) and OS (not reached vs 43 months respectively; p=0.102). On MVA, USC histology and p53abn were significant independent predictors of survival (p=0.03 and p=0.05, respectively). Conclusions: Tumors with p53abn are found in more than half of Caribbean-Black EC patients, with an overrepresentation of aggressive type II histologies in this population compared to those previously reported in the general population. Although not reaching statistical significance, there is a trend towards worse survival outcomes in these p53abn tumors. Further studies are warranted to evaluate EC adjuvant therapy in the context of molecular profiles to improve outcomes for this high-risk patient population. Objectives: To characterize the molecular profiles of endometrial cancer (EC) and correlate with clinical outcomes in a Caribbean- Black patient population. Methods: A multi-center retrospective analysis of Caribbean-Black patients with surgically staged EC from 2015-2021 was conducted. All patients underwent comprehensive surgical staging and/or tumor debulking and molecular tumor profiling performed on pathologic specimens via next-generation sequencing (NGS). Tumors were classified based on TCGA/ProMisE classification: MMR deficient (MMR-d/ MSI-H), p53 abnormal (p53abn), p53 wild type (p53wt), and POLE mutated (POLEmut). Differences in the frequencies of histologic subtypes, stage distribution, and adjuvant therapy were compared using Pearson’s Chi-square test. Progression-free survival (PFS) and overall survival (OS) rates were calculated between p53abn versus other mutational profiles (p53wt and MMR-d/MSI-H) using Kaplan- Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. Results: Of the 119 patients meeting inclusion criteria, the final analysis included 76 patients with complete follow-up data. Tumors were classified as MMR-d/MSI-H (n=11, 14.5%), p53abn (n=43, 56.6%), p53wt (n=21, 27.6%), and POLEmut (n=1, 1.3%). The median age at diagnosis was 64 years (range: 26-82). Histology included 44.0% endometrioid, 47.5% uterine serous (USC), 14.5% carcinosarcoma, and 8.5% clear cell adenocarcinomas. There was no significant difference in the stage distribution between different mutation profiles (p=0.725). USC tumors were associated with p53abn, and endometrioid tumors were associated with MMR-d/MSI-H (p<0.01). All carcinosarcoma patients were p53abn. Patients with p53abn tumors were significantly more likely to receive chemotherapy alone or in combination with radiotherapy versus all other cohorts (p<0.01). One patient with stage IA endometrioid tumor demonstrated POLEmut; this patient remains recurrence-free without adjuvant therapy and was excluded from survival analyses. When compared to all other mutational profiles, p53abn tumors trended towards poorer PFS (29 vs 22 months, respectively; p=0.209) and OS (not reached vs 43 months respectively; p=0.102). On MVA, USC histology and p53abn were significant independent predictors of survival (p=0.03 and p=0.05, respectively). Conclusions: Tumors with p53abn are found in more than half of Caribbean-Black EC patients, with an overrepresentation of aggressive type II histologies in this population compared to those previously reported in the general population. Although not reaching statistical significance, there is a trend towards worse survival outcomes in these p53abn tumors. Further studies are warranted to evaluate EC adjuvant therapy in the context of molecular profiles to improve outcomes for this high-risk patient population.