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MCM2, MCM4, and MCM6 in Breast Cancer: Clinical Utility in Diagnosis and Prognosis
- Source :
- Neoplasia: An International Journal for Oncology Research, Vol 21, Iss 10, Pp 1015-1035 (2019), Neoplasia (New York, N.Y.)
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- Breast cancer is a heterogeneous disease comprising the estrogen receptor (ER)–positive luminal subtype which is subdivided into luminal A and luminal B and ER-negative breast cancer which includes the triple-negative subtype. This study has four aims: 1) to examine whether Minichromosome Maintenance (MCM)2, MCM4, and MCM6 can be used as markers to differentiate between luminal A and luminal B subtypes; 2) to study whether MCM2, MCM4, and MCM6 are highly expressed in triple-negative breast cancer, as there is an urgent need to search for surrogate markers in this aggressive subtype, for drug development purposes; 3) to compare the prognostic values of these markers in predicting relapse-free survival; and 4) to compare the three approaches used for scoring the protein expression of these markers by immunohistochemistry (IHC). MCM2, MCM4, MCM6, and MKI67 mRNA expression was first studied using in silico analysis of available breast cancer datasets. We next used IHC to evaluate their protein expression on tissue microarrays using three scoring methods. MCM2, MCM4, and MCM6 can help in distinction between luminal A and luminal B whose therapeutic management and clinical outcomes are different. MCM2, MCM4, MCM6, and Ki-67 are highly expressed in breast cancer of high histological grades that comprise clinically aggressive tumors such as luminal B, HER2-positive, and triple-negative subtypes. Low transcript expression of these markers is associated with increased probability of relapse-free survival. A positive relationship exists among the three scoring methods of each of the four markers. An independent validation cohort is needed to confirm their clinical utility.
- Subjects :
- 0301 basic medicine
Oncology
Cancer Research
%, percentage score
ER, estrogen receptor
Vis.Tis.S., Visiomorph Tissuemorph score
Estrogen receptor
Gene Expression
Disease
Kaplan-Meier Estimate
0302 clinical medicine
MCM, Minichromosome Maintenance
HER2, human epidermal growth factor receptor 2
Tissue microarray
biology
Prognosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Immunohistochemistry
DP, digital pathology
Drug development
030220 oncology & carcinogenesis
Disease Progression
IHS, Immunohistochemical score
Female
IHC, immunohistochemistry
medicine.medical_specialty
Original article
In silico
Breast Neoplasms
lcsh:RC254-282
03 medical and health sciences
Breast cancer
Internal medicine
medicine
Biomarkers, Tumor
TMA, tissue microarray
Humans
FFPE, formalin-fixed, paraffin-embedded
Neoplasm Staging
business.industry
MCM6
Gene Expression Profiling
Computational Biology
Minichromosome Maintenance Complex Component 2
medicine.disease
Survival Analysis
Minichromosome Maintenance Complex Component 4
030104 developmental biology
Ki-67 Antigen
SBR-EE, Scarff-Bloom-Richardson-Elston-Ellis
biology.protein
TCGA, The Cancer Genome Atlas
Neoplasm Grading
HPS, hematoxylinphloxine saffron
business
Subjects
Details
- Language :
- English
- ISSN :
- 14765586
- Volume :
- 21
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Neoplasia: An International Journal for Oncology Research
- Accession number :
- edsair.doi.dedup.....542355ea565d70c766ba7599ccc806ab