An immunohistochemical evaluation of the proteins Wnt1 and glycogen synthase kinase (GSK)-3β in invasive breast carcinomas

Histopathology. 2013 May;62(6):899-907. doi: 10.1111/his.12095. Epub 2013 Mar 28.

Abstract

Aims: Our purpose was to investigate, in breast carcinomas, the prognostic importance of the proteins Wnt1 and glycogen synthasekinase (GSK)-3β, and their associations with classic clinicopathological indices.

Methods and results: Immunohistochemistry was performed on paraffin-embedded tissue specimens from 288 invasive breast carcinomas to detect the expression of the proteins Wnt1, GSK3β, oestrogen receptor (ER), progesterone receptor (PR), erbB2, p53, Ki67, caspase-3 and β-catenin. Both Wnt1 and GSK3β were detected predominantly in the cytoplasm of the invasive tumour cells and the in-situ component, while GSK3β was also detected in the stromal fibroblasts. Wnt1 immunoreactivity in the invasive tumour cells showed an inverse association with histological grade (P = 0.002), Ki67 (P = 0.008) and p53 (P = 0.031), while its relation with ER, erbB2 and caspase-3 was found to be positive (P = 0.007, P = 0.018 and P = 0.03, respectively). Cytoplasmic Wnt1 expression was related to a favourable prognosis within the subgroup of patients with stage II disease (P = 0.032).

Conclusions: Wnt1 expression in the invasive tumour cells seems to promote differentiation and apoptosis, while being related inversely to proliferation. Therefore, this suggests its participation in the primary stages of breast carcinogenesis. The latter is supported further by the immunodetection of Wnt1 in in-situ carcinomas.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Lobular / metabolism*
  • Carcinoma, Lobular / pathology
  • Cell Differentiation
  • Cell Proliferation
  • Female
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Prognosis
  • Wnt Signaling Pathway
  • Wnt1 Protein / metabolism*

Substances

  • Biomarkers, Tumor
  • WNT1 protein, human
  • Wnt1 Protein
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3