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Impact of lower uterine segment involvement in type II endometrial cancer and the unique mutational profile of serous tumors

OBJECTIVE: Evaluation of the impact of lower uterine segment involvement (LUSI) in type II endometrial cancer, and mutational profile of uterine papillary serous carcinomas (UPSC). METHODS: Retrospective cohort study comparing patients with type II endometrial cancer with LUSI to patients without LU...

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Detalles Bibliográficos
Autores principales: Kogan, Liron, Octeau, David, Amajoud, Zainab, Abitbol, Jeremie, Laskov, Ido, Ferenczy, Alex, Pelmus, Manuela, Eisenberg, Neta, Kessous, Roy, Lau, Susie, Yasmeen, Amber, Gotlieb, Walter H., Salvador, Shannon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003406/
https://www.ncbi.nlm.nih.gov/pubmed/29915797
http://dx.doi.org/10.1016/j.gore.2018.03.004
Descripción
Sumario:OBJECTIVE: Evaluation of the impact of lower uterine segment involvement (LUSI) in type II endometrial cancer, and mutational profile of uterine papillary serous carcinomas (UPSC). METHODS: Retrospective cohort study comparing patients with type II endometrial cancer with LUSI to patients without LUSI. Genes commonly implicated in carcinogenesis were analyzed in a subgroup of 42 patients with UPSC using next generation sequencing. RESULTS: 83 patients with type II endometrial cancer were included in the study, of these, LUSI was diagnosed in 31.3%. During a median follow-up of 45.5 months, patients with LUSI developed more local and distant recurrences (local: 19.2% vs. 3.5%, P = .03; distant: 50% vs. 17.5%, P = .004) and progression events (73.1% vs. 26.3%, P < .001), with shorter mean progression-free survival (16 months compared to 26.5 months, P < .01). In a multivariate analysis, LUSI was the only significant pathological factor, associated with a 2.9-fold increase in the risk of progression (P = .007), and a 2.6-fold increase in the risk of death (P = .02). In the subgroup of patients with UPSC, mutations were identified in 54 genes, including TP53 (80%), PPP2R1A (40%), and PTEN (22.5%). Frequent mutations in the PTEN-PI3K-AKT signaling pathway were found in patients with tumor in the upper uterine segment only (P = .04), with PTEN being mutated in 29% of the samples (P = .07). CONCLUSION: Type II endometrial cancers presenting in the LUS have a significantly worse prognosis and this might be associated with a unique mutational profile.