In situ localization of tumor cells associated with the epithelial-mesenchymal transition marker Snail and the prognostic impact of lymphocytes in the tumor microenvironment in invasive ductal breast cancer

Exp Mol Pathol. 2017 Apr;102(2):268-275. doi: 10.1016/j.yexmp.2017.02.013. Epub 2017 Feb 21.

Abstract

Purpose: Tumor surgery is aimed at complete resection of the lesion while ensuring a sufficient tumor-specific safety distance. Nevertheless, in many cases the most peripheral part - the invasion front - remains in situ. Tumor cells at the tumor margin have been reported to lose their epithelial properties and acquire features of mesenchymal cells. The process of epithelial-to-mesenchymal transition (EMT) is believed to be of prime importance for tissue and vessel invasion. Furthermore, the detection of tumor-infiltrating lymphocytes in the microenvironment of breast cancer might serve as a reliable prognostic marker.

Methods: We investigated tissue microarrays of 352 breast cancer patients with regard to the presence and distribution of the EMT factor Snail, and the presence of FoxP3, CD3 and CD8 in the immune microenvironment.

Results: The expression of the transcription factor Snail is strongly associated with longer disease-free and overall survival. The presence of CD3, CD8 or FoxP3 is associated with a better outcome, although statistically significant results were noted only for FoxP3. The prognostic significance of FoxP3 and Snail were also proven in multivariate analysis.

Conclusions: Based on previous studies concerning the intratumoral heterogeneity of EMT, our results suggest that Snail and FoxP3 are possible prognostic markers for breast cancer. The diverse presence of lymphocytes in the tumor microenvironment (CD3 and CD8) was confirmed. Although the importance of these markers is known, their specific role in tumor invasion and metastasis as well as their hierarchical organization in these tumors remain unclear.

Keywords: Breast cancer; CD3; CD8; Epithelial-to-mesenchymal transition; FoxP3; Microenvironment; Prognostic factor; Snail; Tissue microarray; Tumor heterogeneity.

MeSH terms

  • Biomarkers, Tumor
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / pathology
  • CD3 Complex / genetics
  • CD3 Complex / metabolism
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition*
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Genetic Markers
  • Humans
  • Lymphocytes, Tumor-Infiltrating / cytology*
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proportional Hazards Models
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism*
  • Socioeconomic Factors
  • Tissue Array Analysis
  • Tumor Microenvironment*

Substances

  • Biomarkers, Tumor
  • CD3 Complex
  • CD8 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Genetic Markers
  • Snail Family Transcription Factors