PMID- 29243125 OWN - NLM STAT- MEDLINE DCOM- 20180508 LR - 20220321 IS - 1432-2307 (Electronic) IS - 0945-6317 (Linking) VI - 472 IP - 4 DP - 2018 Apr TI - Minichromosome maintenance complex component 6 (MCM6) expression correlates with histological grade and survival in endometrioid endometrial adenocarcinoma. PG - 623-633 LID - 10.1007/s00428-017-2278-9 [doi] AB - Minichromosome maintenance complex component 6 (MCM6) is involved in initiating DNA replication and is upregulated during licensed G0 phase of the cell cycle. This early expression permits its labeling of more proliferating cells than those by Ki-67. Here using a cohort of 89 endometrioid adenocarcinoma, we report findings made on the prognostic value of MCM6 based on immunohistochemical labeling index (LI) of the protein in comparison with that of Ki67 as no such information is currently available. Additionally, we examined the prognostic values of these markers based on their mRNA expression using a cohort of uterine corpus endometrial carcinoma (UCEC, n = 307) taken from The Cancer Genome Atlas (TCGA) database. Our evidence indicated the presence of a positive correlation between the LI of MCM6 and the histological grade of endometrioid endometrial adenocarcinoma (grade I, 66.7%; grade II, 75.3%; grade III, 81.4%; p < 0.001) and an inverse correlation between the LI of MCM6 and the overall and progression-free survival (p = 0.02 for both). The LI of Ki-67 correlated with grade (p < 0.001), but not survival. The MCM6 and Ki-67 inter-observer intra-class correlation coefficients were excellent: 0.84 (95% confidence interval, 0.83-0.91) and 0.84 (0.77-0.90), respectively. For in silico analyses of the TCGA cohort, both univariate and multivariate Cox analyses (p = 0.003 and p = 0.03, respectively) revealed high MCM6 mRNA Z-scores associated with reduced overall survival. This association was absent for Ki-67. MCM6 is thus a highly reproducible marker of poor prognosis in endometrial cancer. Evaluation of MCM6 should thus be considered in daily practice for risk stratification. FAU - Hotton, Judicael AU - Hotton J AD - Department of Gynecology and Obstetrics, CHRU de Nancy, Nancy, France. AD - INSERM U954, Universite de Lorraine, Vandoeuvre-les-Nancy, France. FAU - Agopiantz, Mikael AU - Agopiantz M AD - INSERM U954, Universite de Lorraine, Vandoeuvre-les-Nancy, France. AD - Department of Medical Gynecology, CHRU de Nancy, Nancy, France. FAU - Leroux, Agnes AU - Leroux A AD - Department of Pathology, Institut de Cancerologie de Lorraine, Vandoeuvre-les-Nancy, France. FAU - Charra-Brunaud, Claire AU - Charra-Brunaud C AD - Department of Radiotherapy, Institut de Cancerologie de Lorraine, Vandoeuvre-les-Nancy, France. FAU - Marie, Beatrice AU - Marie B AD - Department of Pathology, CHRU de Nancy, Nancy, France. FAU - Busby-Venner, Helene AU - Busby-Venner H AD - INSERM U954, Universite de Lorraine, Vandoeuvre-les-Nancy, France. AD - Department of Pathology, CHRU de Nancy, Nancy, France. FAU - Morel, Olivier AU - Morel O AD - Department of Gynecology and Obstetrics, CHRU de Nancy, Nancy, France. FAU - Gueant, Jean-Louis AU - Gueant JL AD - INSERM U954, Universite de Lorraine, Vandoeuvre-les-Nancy, France. AD - Department of Molecular Medicine and Personalized Therapeutics, Department of Biochemistry, Molecular Biology, Nutrition, and Metabolism, CHRU de Nancy, Vandoeuvre-les-Nancy, France. FAU - Vignaud, Jean-Michel AU - Vignaud JM AD - INSERM U954, Universite de Lorraine, Vandoeuvre-les-Nancy, France. AD - Department of Pathology, CHRU de Nancy, Nancy, France. FAU - Battaglia-Hsu, Shyue-Fang AU - Battaglia-Hsu SF AD - INSERM U954, Universite de Lorraine, Vandoeuvre-les-Nancy, France. FAU - Gauchotte, Guillaume AU - Gauchotte G AUID- ORCID: 0000-0001-5585-9195 AD - INSERM U954, Universite de Lorraine, Vandoeuvre-les-Nancy, France. g.gauchotte@chru-nancy.fr. AD - Department of Pathology, CHRU de Nancy, Nancy, France. g.gauchotte@chru-nancy.fr. AD - Service d'Anatomie et Cytologie Pathologiques, Hopital Central, CHRU de Nancy, 29, avenue du Marechal De Lattre de Tassigny, 54000, Nancy, France. g.gauchotte@chru-nancy.fr. LA - eng PT - Journal Article DEP - 20171214 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 RN - 0 (Biomarkers, Tumor) RN - EC 3.6.4.12 (MCM6 protein, human) RN - EC 3.6.4.12 (Minichromosome Maintenance Complex Component 6) SB - IM MH - Aged MH - Biomarkers, Tumor/*analysis MH - Carcinoma, Endometrioid/mortality/*pathology MH - Cohort Studies MH - Disease-Free Survival MH - Endometrial Neoplasms/mortality/pathology MH - Female MH - Humans MH - Middle Aged MH - Minichromosome Maintenance Complex Component 6/analysis/*biosynthesis MH - Prognosis MH - Retrospective Studies OTO - NOTNLM OT - Endometrial carcinoma OT - Endometrioid adenocarcinoma OT - Immunohistochemistry OT - Ki-67 OT - MCM6 OT - Proliferation EDAT- 2017/12/16 06:00 MHDA- 2018/05/09 06:00 CRDT- 2017/12/16 06:00 PHST- 2017/09/05 00:00 [received] PHST- 2017/12/04 00:00 [accepted] PHST- 2017/11/30 00:00 [revised] PHST- 2017/12/16 06:00 [pubmed] PHST- 2018/05/09 06:00 [medline] PHST- 2017/12/16 06:00 [entrez] AID - 10.1007/s00428-017-2278-9 [pii] AID - 10.1007/s00428-017-2278-9 [doi] PST - ppublish SO - Virchows Arch. 2018 Apr;472(4):623-633. doi: 10.1007/s00428-017-2278-9. Epub 2017 Dec 14.