Loss of MDC1 in Endometrial Carcinoma Is Associated With Loss of MRN Complex and MMR Deficiency

Anticancer Res. 2019 Dec;39(12):6547-6553. doi: 10.21873/anticanres.13870.


Aim: To evaluate the frequency of loss of mediator of DNA damage checkpoint protein 1 (MDC1) protein expression in endometrial cancer (EC) and to determine whether loss of MDC1 is associated with certain clinicopathological parameters.

Materials and methods: MDC1 expression was examined in 426 samples of EC. The nuclear immunoreactivity of the protein was defined as: negative, weak, moderate and strong.

Results: Loss of MDC1 expression (defined as negative nuclear staining) was found in 8.9% (38/426) of ECs and was significantly associated with the loss of MRE11 homolog, double-strand break repair nuclease, RAD50 double-strand break repair protein and nibrin complex components. In addition, loss of expression of MDC1 showed a significant correlation with any mismatch repair deficiency, with endometrioid histological subtype and low tumour grading.

Conclusion: Based on these findings, we suggest that MDC1 loss frequently occurs in ECs with microsatellite instability. Due to deficient homologous recombination DNA repair, MDC1-negative ECs might show an increased sensitivity to poly(ADP-ribose) polymerase-inhibitory therapy.

Keywords: MDC1; PARP; endometrial carcinoma; mismatch repair; targeted therapy.

MeSH terms

  • Acid Anhydride Hydrolases
  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins / deficiency*
  • DNA Mismatch Repair
  • DNA Repair Enzymes / deficiency*
  • DNA-Binding Proteins / deficiency*
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MRE11 Homologue Protein / deficiency*
  • Microsatellite Instability
  • Neoplasm Staging
  • Nuclear Proteins / deficiency*
  • Nuclear Proteins / metabolism*
  • Survival Analysis
  • Tissue Array Analysis
  • Trans-Activators / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MDC1 protein, human
  • NBN protein, human
  • Nuclear Proteins
  • Trans-Activators
  • MRE11 Homologue Protein
  • Acid Anhydride Hydrolases
  • Rad50 protein, human
  • DNA Repair Enzymes