期刊
VIRCHOWS ARCHIV
卷 480, 期 4, 页码 855-871出版社
SPRINGER
DOI: 10.1007/s00428-021-03232-0
关键词
High-grade serous carcinoma; Proliferation; MCM3
类别
资金
- Alberta Precision Laboratory [RS19-612, RS10-526]
- National Institutes of Health/National Cancer Institute (NCI) [R01CA172404]
- Heuer Stiftung fur medizinische Forschung
- NSW Ministry of Health
- UNSW Sydney under the NSW Health PhD Scholarship Program
- Translational Cancer Research Network, a translational cancer research center program- Cancer Institute NSW
- Michael Smith Foundation for Health Research Scholar Award
- Janet D. Cottrelle Foundation Scholars program
- BC Cancer Foundation
- VGH + UBC Hospital Foundation
- US National Cancer Institute [K07-CA80668, R01CA095023, R01 CA126841]
- US Army Medical Research and Materiel Command [DAMD17-02-1-0669]
- NIH/National Center for Research Resources/General Clinical Research Center grant [MO1RR000056]
- University of Pittsburgh Dean's Faculty Advancement Fund
- American Cancer Society [SIOP-06-258-01-COUN]
- Westmead Hospital Department of Gynaecological Oncology
- National Health and Medical Research Council [310,670, 628,903]
- Cancer Institute NSW [12/RIG/1-17, 15/RIG/1-16]
- West Translational Cancer Research Centre
- Breast Cancer Now
- Institute of Cancer Research (ICR)
- NHS
- Swedish Cancer foundation
- Swedish government
- Swedish county council, the ALF-agreement
- Assar Gabrielsson foundation
- U.S. Defense Health Program [HU0001-16-20006, HU0001-19-2-0031]
- Translational Cancer Research Network (TCRN), a Translational Cancer Research Centre - Cancer Institute NSW
- Dutch Cancer Society [IKNL2014-6838]
- NCI [P30CA014089]
- [P50-CA135393]
- [R01-CA248288]
MCM3 mRNA and protein expression levels are associated with survival in patients with tubo-ovarian high-grade serous carcinomas (HGSC), showing a correlation between high MCM3 expression and longer overall survival.
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-naive 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-naive tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naive 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.
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