TY - JOUR
T1 - Less is more? Comparison between genomic profiling and immunohistochemistry-based models in endometrial cancer molecular classification: A multicenter, retrospective, propensity-matched survival analysis
AU - Perrone, E
AU - Tarantino, Vincenzo
AU - Esposito, G
AU - Palmieri, L
AU - Guaita, A
AU - van Rompuy, As
AU - Scaglione, Giulia
AU - Capasso, I
AU - Giannarelli, Diana
AU - Trozzi, Rita
AU - Congedo, L
AU - Ervas, Elisa
AU - Zannoni, Gian Franco
AU - Scambia, Giovanni
AU - Amant, F
AU - Fanfani, Francesco
PY - 2024
Y1 - 2024
N2 - Background: Genomic profiling-based model (GP-M) is the gold-standard for endometrial cancer (EC) molecular classification, but several issues related to the availability of genomic sequencing in low-income settings remain and health disparities in the management are increasing. This study aims to investigate the non-inferiority of the immunohistochemistry-alone model in classifying ECs compared to the standard genomic profiling-based model in terms of oncologic outcomes. Methods: All preoperative uterine-confined ECs undergoing surgical staging were retrospectively included. Patients classified by IHC-M were stratified into: MMR-proficient (MMRp), p53 wild type (p53wt) and estrogen receptor (ER) positive, 2) MMRp, p53wt and ER-negative, 3) MMRd, and 4) p53abn. A case-control comparison was performed between the IHC-M and GP-M cohorts. Then, a propensity-matched analysis was performed: ECs classified by IHC-M were matched in a 3:1 ratio with patients classified by GP-M. Results: 1587 patients with EC were included. The Kaplan-Meier survival curves for disease-free survival and overall survival demonstrated that the two models performed similarly in risk-stratifying the study population (p < 0.0001). Moreover, the AUC-ROC showed overlapping results: 0.77 (0.66-0.87) for IHC-M and 0.72 (0.63-0.81) for GP-M, indicating that both models were able to successfully identify patients at high-risk and low-risk of disease recurrence/progression. Conclusion: The IHC-M showed overlapping classification performance compared to the GP-M in terms of oncologic outcomes. This study may lay the basis to further investigate the real-life clinical impact of POLE sequencing in molecular classification and the potential stand-alone prognostic role of ER status for further allocation of EC patients into risk classes.
AB - Background: Genomic profiling-based model (GP-M) is the gold-standard for endometrial cancer (EC) molecular classification, but several issues related to the availability of genomic sequencing in low-income settings remain and health disparities in the management are increasing. This study aims to investigate the non-inferiority of the immunohistochemistry-alone model in classifying ECs compared to the standard genomic profiling-based model in terms of oncologic outcomes. Methods: All preoperative uterine-confined ECs undergoing surgical staging were retrospectively included. Patients classified by IHC-M were stratified into: MMR-proficient (MMRp), p53 wild type (p53wt) and estrogen receptor (ER) positive, 2) MMRp, p53wt and ER-negative, 3) MMRd, and 4) p53abn. A case-control comparison was performed between the IHC-M and GP-M cohorts. Then, a propensity-matched analysis was performed: ECs classified by IHC-M were matched in a 3:1 ratio with patients classified by GP-M. Results: 1587 patients with EC were included. The Kaplan-Meier survival curves for disease-free survival and overall survival demonstrated that the two models performed similarly in risk-stratifying the study population (p < 0.0001). Moreover, the AUC-ROC showed overlapping results: 0.77 (0.66-0.87) for IHC-M and 0.72 (0.63-0.81) for GP-M, indicating that both models were able to successfully identify patients at high-risk and low-risk of disease recurrence/progression. Conclusion: The IHC-M showed overlapping classification performance compared to the GP-M in terms of oncologic outcomes. This study may lay the basis to further investigate the real-life clinical impact of POLE sequencing in molecular classification and the potential stand-alone prognostic role of ER status for further allocation of EC patients into risk classes.
KW - Uterine neoplasm
KW - Endometrial cancer
KW - Surgery
KW - Immunohistochemistry
KW - Molecular classification
KW - Uterine neoplasm
KW - Endometrial cancer
KW - Surgery
KW - Immunohistochemistry
KW - Molecular classification
UR - http://hdl.handle.net/10807/305363
U2 - 10.1016/j.ygyno.2024.10.010
DO - 10.1016/j.ygyno.2024.10.010
M3 - Article
SN - 0090-8258
VL - 191
SP - 150
EP - 157
JO - Gynecologic Oncology
JF - Gynecologic Oncology
ER -