Nodal metastasis signatures in breast cancer

Pathol Res Pract. 2017 Jun;213(6):680-687. doi: 10.1016/j.prp.2016.11.017. Epub 2016 Dec 5.


Although the molecular taxonomy of invasive breast cancer is based on heterogeneous histologic types, pathologic nodal (pN) stage remains one of the most important independent prognostic factors. Although node-positive number (NPN) has been widely as an accepted staging algorithm of pN stage, the node-positive ratio (NPR) in totally resected axillary nodes has been considered as another reasonable indicator. We aimed to identify signatures to play a predictive role in nodal metastasis for analytic validation between the primary breast cancers with positive node metastasis and those with negative node metastasis. We validated expression profiles of surrogate candidates extracted from the prior 2D MALDI-TOF data for invasive breast cancer using fluorescence/silver in situ hybridization (FISH/SISH) and immunohistochemistry (IHC) in 151 primary breast cancers accompanied with 102 metastatic nodal tissues. Cox proportional hazards regression analyses indicated that event factors (recurrence or metastasis) were significantly more frequent in cases with CCDN1, c-myc gene amplification, IgHA2 low expression. CCDN1 gene amplification (OR: 5.702, p=0.0006), IgHA2 low expression (OR: 0.16, p=0.0184) remained significant factors for events on multivariate analyses. WDR+/ERK++ was significantly detected in higher pN stage (averaging 6.5 regional nodes or 43% of NPR), while seldom found in pN0-1. In conclusion, both overexpression of WDR1 and p-ERK in the primary breast cancer could play a role in the nodal signature over pN2-3.

Keywords: Breast cancer; ERK; Node positive number; Node positive ratio; WDR1; c-MET.

MeSH terms

  • Aged
  • Biomarkers, Tumor
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology*
  • Disease-Free Survival
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Genes, myc
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization / methods
  • Lymph Node Excision
  • Lymphatic Metastasis / pathology*
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Phosphorylation
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Survival Rate


  • Biomarkers, Tumor
  • Microfilament Proteins
  • WDR1 protein, human
  • Extracellular Signal-Regulated MAP Kinases