MCM6 versus Ki-67 in diagnosis of luminal molecular subtypes of breast cancers

Diagn Pathol. 2022 Feb 6;17(1):24. doi: 10.1186/s13000-022-01209-4.


Background: Currently, breast cancers are divided into four major molecular subtypes. The distinction between the luminal A and luminal B subtypes is mainly based on the cellular proliferation indices and is assessed by the Ki-67 scoring. Due to the limitations in the assessment and expression of Ki-67, we hypothesized that minichromosome maintenance protein 6 (MCM6) might be taken as a surrogate marker to differentiate molecular subtypes and aid in more precise grading of tumors.

Methods: We performed a retrospective, cross-sectional study on 124 samples of breast cancer and 40 samples of normal breast tissue. Relevant clinical information was retrieved from the Cancer Institute database.

Results: MCM6 could discriminate between various categories of histologic grades, tubule formation, mitotic indices, and nuclear pleomorphism (P = 0.002 for tubule formation and P < 0.001 for other). Moreover, the MCM6 score exhibited a significant correlation with the mitotic count (P < 0.001). However, the Ki-67 score could not discriminate subgroups of the mitotic index and nuclear pleomorphism. Compared to the luminal A subtype, luminal B exhibited a higher MCM6 score (P = 0.01). Besides, MCM6 scores were higher for certain subtypes with more aggressive behaviors, such as hormone receptor (HR)-negative disease, and human epidermal growth factor receptor 2 (HER2)-enriched and triple-negative breast cancers, as there was a significantly higher MCM6 mean score in the HR-negative in comparison to the luminal breast cancers (P < 0.001). Similarly, higher MCM6 scores were observed among samples with more advanced nuclear grades, tubule formation, and overall grades.

Conclusion: MCM6 can differentiate luminal A and luminal B subtypes and is correlated with mitotic counts. However, this study was unable to prove the superiority of MCM6 in differentiating between molecular subtypes compared to the Ki-67 score. Nevertheless, in our study, MCM6 was superior to Ki-67 in exhibiting correlations with the mitotic grade, tubule formation, and nuclear grades. More studies are needed to standardize its assessment methods, determine more robust cut-off values, and evaluate its associations with prognostic features of breast cancer.

Keywords: Biomarkers; Breast cancer; Diagnostic; Ki67; Luminal B; Luminal a; MCM6.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / genetics
  • Cross-Sectional Studies
  • Female
  • Humans
  • Ki-67 Antigen / metabolism
  • Minichromosome Maintenance Complex Component 6
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Progesterone / metabolism
  • Retrospective Studies


  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Receptors, Progesterone
  • Receptor, ErbB-2
  • MCM6 protein, human
  • Minichromosome Maintenance Complex Component 6