Clinicopathologic characteristics of STAT1 positive/interleukin-8 negative subgroup in triple negative breast cancer defined by surrogate immunohistochemistry

Histol Histopathol. 2013 Nov;28(11):1461-71. doi: 10.14670/HH-28.1461. Epub 2013 May 15.

Abstract

Background: The aim of this study was to define immune-related triple negative breast cancer (TNBC) using immunohistochemistry for STAT1, CD20, CD3, IL-8, and IFN-γ and to assess its clinicopathologic characteristics.

Material and methods: Tissues from 133 cases of TNBC were used for a tissue microarray. Expression of STAT1, CD20, CD3, IL-8, and IFN-γ were evaluated by immunohistochemical staining of the tissue microarrays. Immune-related type was defined as TNBC which was positive for STAT1 and negative for IL-8. A separate assessment of IL-8 and STAT1 status in tumor and stroma compartment was used to further classify immune-related type into tumor-based and stroma-based immune-related TNBC.

Results: Stroma-based, immune-related TNBC showed a significantly smaller central acellular zone (p=0.043), more lymphocytic infiltration (p⟨0.001), higher CD20 index (p=0.001), and higher CD3 index (p=0.018) than stroma-based, non-immune-related TNBC. IL-8 was independently associated with shorter disease-free survival (Hazard ratio: 3.804, 95% CI: 1.234-11.729, p=0.020) and shorter overall survival (Hazard ratio: 3.434, 95% CI: 1.132-10.414, p=0.029).

Conclusions: Immune-related proteins such as STAT1, IFN-γ, IL-8, and CD20 were variably expressed in TNBCs. Stroma-based, immune-related TNBC (when positive for stromal STAT1 and negative for stromal IL-8) showed significantly higher lymphocytic infiltration including both CD3 positive T cell and CD20 positive B cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / immunology*
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Interleukin-8 / biosynthesis
  • Kaplan-Meier Estimate
  • Middle Aged
  • STAT1 Transcription Factor / biosynthesis
  • Tissue Array Analysis
  • Triple Negative Breast Neoplasms / classification*
  • Triple Negative Breast Neoplasms / immunology*
  • Triple Negative Breast Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Interleukin-8
  • STAT1 Transcription Factor
  • STAT1 protein, human