Mediator of DNA damage checkpoint protein 1 (MDC1) expression as a prognostic marker for nodal recurrence in early-stage breast cancer patients treated with breast-conserving surgery and radiation therapy.
The mediator of DNA damage checkpoint protein 1 (MDC1) regulates cell cycle checkpoints and recruits repair proteins to sites of double-stranded DNA damage using its BRCA1 carboxy-terminal (BRCT) domains. MDC1 under-expression has been associated with radiosensitivity in cells. The purpose of this study was to evaluate the clinico-pathologic and prognostic significance of MDC1 expression in a cohort of early-stage breast cancer patients treated with breast conservation therapy. Paraffin specimens from 489 women with early-stage breast cancer treated with breast conservation therapy were constructed into tissue microarrays. The arrays were stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and MDC1. This was correlated with clinico-pathologic factors and outcomes. MDC1 expression was evaluable in 351 cases (72%). Decreased MDC1 expression was found to be correlated with nodal failure (P = 0.05), but not ipsilateral breast relapse-free survival (IBRFS), distant metastasis-free survival (DMFS), or overall survival (OS). Subset analysis in node-negative patients revealed that decreased MDC1 expression predicted for nodal failure (P < 0.01). Our study is the first to assess the clinico-pathologic and prognostic significance of MDC1 expression in patients with early-stage breast cancer treated with lumpectomy and radiotherapy. MDC1 under-expression predicted for nodal failure, but not for IBRFS, DM, or OS. The role of other proteins involved in the DNA damage repair pathway and their effects on MDC1 expression, as well as the level of MDC1 expression in patients with BRCA1 mutations warrant further investigation.
Patel
Akshar N
AN
Department of Radiation Oncology, UMDNJ-Robert Wood Johnson Medical School and The Cancer Instititute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
Goyal
Sharad
S
Wu
Hao
H
Schiff
Devora
D
Moran
Meena S
MS
Haffty
Bruce G
BG
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D019313:BRCA1 Protein / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery*; D018797:Cell Cycle Proteins; D004249:DNA Damage; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D012008:Recurrence; D015534:Trans-Activators / Q000096:biosynthesis*
D048868:Adaptor Proteins, Signal Transducing; D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015534:Trans-Activators; C492913:BRCA1 protein, human; C413163:MDC1 protein, human; C508053:ERBB2 protein, human