| Literature DB >> 34782936 |
Eun Young Kang1, Joshua Millstein2, Gordana Popovic3, Nicola S Meagher4,5, Adelyn Bolithon4,5, Aline Talhouk6,7,8, Derek S Chiu6, Michael S Anglesio7,8,9, Betty Leung10, Katrina Tang11, Neil Lambie12, Marina Pavanello13, Annalyn Da-Anoy1, Diether Lambrechts14,15, Liselore Loverix16, Siel Olbrecht16, Christiani Bisinotto17, Jesus Garcia-Donas18, Sergio Ruiz-Llorente18, Monica Yagüe-Fernandez18, Robert P Edwards19, Esther Elishaev20, Alexander Olawaiye19, Sarah Taylor19, Beyhan Ataseven21,22, Andreas du Bois21,23, Philipp Harter21,23, Jenny Lester24, Claus K Høgdall25, Sebastian M Armasu26, Yajue Huang27, Robert A Vierkant26, Chen Wang28, Stacey J Winham28, Sabine Heublein29, Felix K F Kommoss30, Daniel W Cramer31,32, Naoko Sasamoto32, Lilian van-Wagensveld33, Maria Lycke34, Constantina Mateoiu35, Janine Joseph36, Malcolm C Pike2,37, Kunle Odunsi38,39, Chiu-Chen Tseng40, Celeste L Pearce2,41, Sanela Bilic42, Thomas P Conrads43, Arndt Hartmann44, Alexander Hein45, Michael E Jones46, Yee Leung47,48,49, Matthias W Beckmann45, Matthias Ruebner45, Minouk J Schoemaker46, Kathryn L Terry31,32, Mona A El-Bahrawy50, Penny Coulson46, John L Etter36, Katherine LaVigne-Mager51, Juergen Andress52, Marcel Grube52, Anna Fischer53, Nina Neudeck53, Greg Robertson4,54, Rhonda Farrell55, Ellen Barlow56, Carmel Quinn3,5,10,57,58, Anusha Hettiaratchi58, Yovanni Casablanca59, Ramona Erber44, Colin J R Stewart60, Adeline Tan47,61, Yu Yu62, Jessica Boros13,63, Alison H Brand63, Paul R Harnett64,65, Catherine J Kennedy13,63, Nikilyn Nevins13,63,65, Terry Morgan66, Peter A Fasching45,67, Ignace Vergote16, Anthony J Swerdlow46,68, Francisco J Candido Dos Reis17, G Larry Maxwell69, Susan L Neuhausen70, Arantzazu Barquin-Garcia18, Francesmary Modugno19,71, Kirsten B Moysich36, Philip J Crowe10, Akira Hirasawa72, Florian Heitz21,23,73, Beth Y Karlan24, Ellen L Goode74, Peter Sinn30, Hugo M Horlings33, Estrid Høgdall75,76, Karin Sundfeldt77, Stefan Kommoss52, Annette Staebler53, Anna H Wu2, Paul A Cohen47,78, Anna DeFazio13,63,64,65, Cheng-Han Lee79, Helen Steed80, Nhu D Le81, Simon A Gayther82, Kate Lawrenson83, Paul D P Pharoah84,85, Gottfried Konecny67, Linda S Cook86,87, Susan J Ramus4,5, Linda E Kelemen88, Martin Köbel89.
Abstract
Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.Entities:
Keywords: High-grade serous carcinoma; MCM3; Proliferation
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Year: 2021 PMID： 34782936 PMCID： PMC9035053 DOI： 10.1007/s00428-021-03232-0
Source DB: PubMed Journal: Virchows Arch ISSN： 0945-6317 Impact factor: 4.535