TY - JOUR
T1 - Impact of lower uterine segment involvement in type II endometrial cancer and the unique mutational profile of serous tumors
AU - Kogan, Liron
AU - Octeau, David
AU - Amajoud, Zainab
AU - Abitbol, Jeremie
AU - Laskov, Ido
AU - Ferenczy, Alex
AU - Pelmus, Manuela
AU - Eisenberg, Neta
AU - Kessous, Roy
AU - Lau, Susie
AU - Yasmeen, Amber
AU - Gotlieb, Walter H.
AU - Salvador, Shannon
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/5
Y1 - 2018/5
N2 - 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.
AB - 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.
KW - Gene analysis
KW - Lower uterine segment
KW - PTEN mutation
KW - Sequencing
KW - Type II endometrial cancer
KW - Uterine papillary serous carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85044749377&partnerID=8YFLogxK
U2 - 10.1016/j.gore.2018.03.004
DO - 10.1016/j.gore.2018.03.004
M3 - Article
AN - SCOPUS:85044749377
SN - 2211-338X
VL - 24
SP - 43
EP - 47
JO - Gynecologic Oncology Reports
JF - Gynecologic Oncology Reports
ER -