Emerging prognostic markers related to mesenchymal characteristics of poorly differentiated breast cancers

Tumour Biol. 2016 Apr;37(4):5427-35. doi: 10.1007/s13277-015-4361-7. Epub 2015 Nov 12.

Abstract

Despite the screening program, breast cancer is the commonest cause of cancer death in women in the industrialized world. In this study, we investigate the correlation among poorly differentiated carcinoma, epithelial to mesenchymal transition (EMT) phenomenon, and expression of NF-kB, Sonic Hedgehog (SHH), K-RAS, and PTX3 in breast cancer in 100 breast biopsies. Samples were classified as follows: 30 benign lesions (BL), 30 ductal infiltrating carcinomas low grade (MLG1), and 40 ductal infiltrating carcinomas high grade (MLG3). Expression of vimentin, CD44, β-catenin, NF-kB, SHH, K-RAS, CD44, and PTX3 was studied by immunohistochemistry. The different rate of cells with vimentin, nuclear β-catenin, and CD44 expression in MLG3 as compared with MLG1 and BL suggested that the process of de-differentiation of breast cancer cells could be related to the EMT. Our results showed a significant increase in NF-kB signal in MLG3 (2.33 ± 0.77) with respect to MLG1 (1.26 ± 0.55) and BL (0.86 ± 0.52). SHH expression appeared low in BL (1.00 ± 0.41) and homogenously widespread in MLG1 (1.23 ± 0.63) and MLG3 (1.56 ± 0.54). An important increase in K-RAS signal was observed in MLG3 compared to that in BL (2.20 ± 0.69 vs 0.82 ± 0.59). As regards PTX3, we observed a strong expression in MLG3 (2.00 ± 0.78) with respect to BL (0.58 ± 0.55) and MLG1 (1.53 ± 0.76). The recurring expression of NF-kB, SHH, K-RAS, and PTX3 in vimentin- and CD44-positive breast cancer cells allows to speculate that breast cells acquire the ability to express these molecules in concomitance to EMT phenomenon.

Keywords: Breast cancer markers; Epithelial to mesenchymal transition; K-RAS; NF-kB; PTX3; Sonic Hedgehog.

MeSH terms

  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • C-Reactive Protein / biosynthesis*
  • C-Reactive Protein / genetics
  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hedgehog Proteins / biosynthesis*
  • Hedgehog Proteins / genetics
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Hyaluronan Receptors / genetics
  • NF-kappa B / biosynthesis
  • NF-kappa B / genetics
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / biosynthesis*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Serum Amyloid P-Component / biosynthesis*
  • Serum Amyloid P-Component / genetics
  • Vimentin / biosynthesis
  • Vimentin / genetics

Substances

  • Biomarkers, Tumor
  • CD44 protein, human
  • Cadherins
  • Hedgehog Proteins
  • Hyaluronan Receptors
  • KRAS protein, human
  • NF-kappa B
  • SHH protein, human
  • Serum Amyloid P-Component
  • Vimentin
  • PTX3 protein
  • C-Reactive Protein
  • Proto-Oncogene Proteins p21(ras)