Immunohistochemical expression of homeoproteins Six1 and Pax3 in breast phyllodes tumours correlates with histological grade and clinical outcome

Histopathology. 2014 May;64(6):807-17. doi: 10.1111/his.12329. Epub 2014 Jan 20.


Aims: Homeoproteins are transcription factors which critically regulate developmental processes. Deregulated expression of homeoproteins is observed in several malignancies, such as breast cancer and rhabdomyosarcoma, and contributes to malignant progression. We aimed to investigate the expression and prognostic importance of Six1 and Pax3 homeoproteins in phyllodes tumours - a group of uncommon biphasic tumours comprising both epithelial and stromal components.

Methods and results: A total of 272 cases diagnosed from January 2003 to December 2010 were included in this study - 189 (69.5%) benign, 60 (22.1%) borderline and 23 (8.4%) malignant tumours. Immunohistochemistry was performed on tissue microarray sections using antibodies against Six1 and Pax3. Staining H-score was assessed in epithelium and stroma separately, and correlated with tumour grade, clinicopathological parameters and prognosis. Tumour grade was associated positively with stromal cytoplasmic expression (P < 0.001; P = 0.011) but correlated negatively with epithelial nuclear expression (P = 0.013; P = 0.007) of both Six1 and Pax3. High stromal cytoplasmic expression of Six1 was associated with metastasis (P = 0.044) and shorter time to recurrence (P = 0.056). Pax3 stromal cytoplasmic expression was associated with poorer overall survival (P = 0.033).

Conclusions: Six1 and Pax3 expression is correlated with tumour grade, unfavourable clinicopathological parameters and poorer clinical outcome, suggesting that both proteins may play a role in malignant progression.

Keywords: Pax3; Six1; immunohistochemistry; phyllodes tumours; prognosis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Disease Progression
  • Female
  • Homeodomain Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Grading
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors / metabolism*
  • Phyllodes Tumor / metabolism*
  • Phyllodes Tumor / pathology
  • Prognosis
  • Tissue Array Analysis
  • Young Adult


  • Biomarkers, Tumor
  • Homeodomain Proteins
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • SIX1 protein, human