A monocentric analysis of ESCAT gene actionability detection in non-specific molecular profile (NSMP) endometrial cancer.
Abstract
e17634 Background: The non-specific molecular profile (NSMP) subtype accounts for 50% of endometrial carcinoma (EC). It's a heterogeneous group of tumors, characterized by minimal cell mutations and low copy number variations, including both aggressive and clinically low-risk ECs. Methods: In January 2022 our institution launched a comprehensive cancer genome profiling (CGP) (FPG500 IRB approval 3837; NCT06020625) enrolling also EC patients. Oncogenic and likely oncogenic alterations were reported according to OncoKB and classified as Tier I-II-III according to ESCAT classification. The aim of the current analysis was to describe ESCAT gene actionability findings. Results: From January 1 st 2022 to December 31 st 2023, 253 patients with any FIGO stage, NSMP ECs were enrolled. Median age was 62 years and the most frequent histotype was endometrioid (96.9%). Estrogen receptors were positive in 94.5%. Overall, 233 patients (92%) had at least one tier III ESCAT alteration. The more frequent variants were found in PTEN (88%), PIK3CA (43%), FGFR2 (15%) and AKT1 (6%). 18% of patients had an ESR1 variant, while a KRAS G12C variant was found in 11% of patients. The majority of PTEN variants were R130X: R130G (40 pts, 17.2%), R130Q (17 pts, 7.3%) and R130* (10 pts, 4.3%). The PIK3CA's more frequently altered hotspots were H1047R (21 pts, 9.0%), E545D/K/Q/A (13 pts, 5.6%) and E542K (9 pts, 3.9%). The most frequent FGFR2 hotspot was S252W (16 pts, 6.9%). Mutually exclusive genes (p<0.05) were AKT and PTEN, PIK3CA and PIK3R1, FGFR2 with CTNNB1 and KRAS. Significant co-occurrence (p<0.05). was found between PTEN and PIK3CA and ARID1A. Considering ESCAT Tiers, the PI3K pathway was altered in 85% of patients. Conclusions: Our descriptive analysis aligns with existing literature data. Further investigation correlating survival and recurrence rates with molecular findings could unveil prognostic subgroups and potentially targetable variants.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (17)
Floriana Camarda
Fondazione Policlinico Universitario A. Gemelli, IRCCS, Division of Gynecologic Oncology, Catholic university of the Sacred Heart, Rome, Italy
Luca Mastrantoni
Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Chiara Parrillo
Bioinformatics Research Core Facility, Gemelli Science and Technology Park (GSTeP), IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
Tina Pasciuto
Marianna Manfredelli
Scientific Directorate, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Rita Trozzi
Anna Fagotti, MD, PhD, and Rita Trozzi, MD, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy, Università Cattolica del Sacro Cuore, Rome, Italy; Diana Giannarelli, PhD, MSc, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy; and Giovanni Scambia, MD, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy, Università Cattolica del Sacro Cuore, Rome, Italy
Luciano Giaco'
Bioinformatics Research Core Facility, Gemelli Science and Technology Park (G-STeP), Fondazione Policlinico Universitario "A. Gemelli," IRCCS, Rome, Italy
Federica Persiani
Bioinformatics Research Core Facility, Gemelli Science and Technology Park (GSTeP), IRCCS Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
Iolanda Mozzetta
Data Collection Research Core Facilty Gemelli Science and Technology Park (GSTeP), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Angelo Minucci
Departmental Unit of Molecular and Genomic Diagnostics, Genomics Core Facility, Gemelli Science and Technology Park (G-STeP), Fondazione Policlinico Universitario "A. Gemelli," IRCCS, Rome, Italy
Elisa De Paolis
Gemelli Science and Technology Park (G-STeP), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Emanuele Perrone
Unit of Gynecologic Oncology, Department Woman and Child Health Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico
Valentina Iacobelli
Fondazione Policlinico Universitario A. Gemelli, IRCCS, Division of Gynecologic Oncology, Catholic university of the Sacred Heart, Rome, Italy
Gian Franco Zannoni
Gynecopathology and Breast Pathology Unit, Department of Women's, Children's and Public Health Sciences, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy; Università Cattolica Del Sacro Cuore, Rome, Italy
Francesco Fanfani
Unit of Gynecologic Oncology, Department Woman and Child Health Sciences and Public Health, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico
Giovanni Scambia
Camilla Nero
Gynecologic Oncology Unit, Department of Women’s and Children’s Health Sciences, Fondazione Policlinico Universitario "A. Gemelli," IRCCS, and Catholic University of the Sacred Heart, Rome, Italy