| Autores |
Pelegrina, Beatriz , Paytubi, Sonia , Marin, Fatima , Martinez, Jose Manuel , CARMONA PESTAÑA, ÁLVARO, Frias-Gomez, Jon , Peremiquel-Trillas, Paula , Dorca, Eduard , Zanca, Alba , Lopez-Querol, Marta , Onieva, Irene , Benavente, Yolanda , Barahona, Marc , Fernandez-Gonzalez, Sergi , De Francisco, Javier , Cano, Victor , Vidal, August , Pijuan, Lara , Canet-Hermida, Julia , Duenas, Nuria , Brunet, Joan , Pineda, Marta , Matias-Guiu, Xavier , Ponce, Jordi , Bosch, Francesc Xavier , De Sanjose, Silvia , Alemany, Laia , Costasa, Laura |
| Abstract |
Background The incidence of endometrial cancer is increasing worldwide. While delays in diagnosis reduce survival, case molecular misclassification might be associated with under-and over-treatment. The objective of this study was to evaluate genetic alterations to detect and molecularly classify cases of endometrial cancer using non-invasive samples.Methods Consecutive patients with incident endometrial cancer (N = 139) and controls (N = 107) from a recent Spanish case-control study were included in this analysis. Overall, 339 cervicovaginal samples (out of which 228 were clinician-collected and 111 were self-collected) were analysed using a test based on next-generation sequencing (NGS), which targets 47 genes. Immunohistochemical markers were evaluated in 133 tumour samples. A total of 159 samples were used to train the detection algorithm and 180 samples were used for validation.Findings Overall, 73% (N = 94 out of 129 clinician-collected samples, and N = 66 out of 90 self-collected samples) of endometrial cancer cases had detectable mutations in clinician-collected and self-collected samples, while the specificity was 80% (79/99) for clinician-collected samples and 90% (19/21) for self-collected samples. The molecular classifications obtained using tumour samples and non-invasive gynaecologic samples in our study showed moderate-to-good agreement. The molecular classification of cases of endometrial cancer into four groups using NGS of both clinician-collected and self-collected cervicovaginal samples yielded significant differences in disease-free survival. The cases with mutations in POLE had an excellent prognosis, whereas the cases with TP53 mutations had the poorest clinical outcome, which is consistent with the data on tumour samples. Interpretation This study classified endometrial cancer cases into four molecular groups based on the analysis of cervicovaginal samples that showed significant differences in disease-free survival. The molecular classification of endometrial cancer in non-invasive samples may improve patient care and survival by indicating the early need for aggressive surgery, as well as reducing referrals to highly specialized hospitals in cancers with good prognosis. Validation in independent sets will confirm the potential for molecular classification in non-invasive samples. Copyright & COPY; 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
