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Stem cell biomarker ALDH1A1 in breast cancer shows an association with prognosis and clinicopathological variables that is highly cut-off dependent
  1. Martin Sjöström1,
  2. Linda Hartman1,
  3. Gabriella Honeth1,
  4. Dorthe Grabau1,2,
  5. Per Malmström1,3,
  6. Cecilia Hegardt1,
  7. Mårten Fernö1,
  8. Emma Niméus1,4
  1. 1Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden
  2. 2Division of Pathology, Skåne University Hospital, Lund, Sweden
  3. 3Division of Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden
  4. 4Division of Surgery, Skåne University Hospital, Lund, Sweden
  1. Correspondence to Dr Emma Niméus, Department of Clinical Sciences Lund, Oncology and Pathology, Medicon Village, By 406, Lund SE-223 81, Sweden; Emma.Nimeus{at}med.lu.se

Abstract

Aims Aldehyde dehydrogenase family 1 member A1 (ALDH1A1) is a putative marker of breast cancer stem cells (CSCs) with prognostic implications when expressed in cancer or stroma. However, previous results are contradictory and we therefore aimed to further evaluate the impact of ALDH1A1 on distant disease-free survival (DDFS) and correlation with clinicopathological variables in breast cancer, specifically by evaluating different cut-offs.

Methods Two breast cancer cohorts (N=216 and N=210) were evaluated with immunohistochemistry for ALDH1A1 on tissue microarrays with three different cut-offs in cancer cells and in stromal cells. The association of ALDH1A1 with DDFS and other clinicopathological variables was assessed. As further validation, gene expression levels of ALDH1A1 and association with survival were analysed in one of the cohorts and a separate cohort.

Results ALDH1A1 expression in cancer cells was associated with either a better or a worse prognosis, depending on cut-off. Considering weakly stained cancer cells as positive, ALDH1A1+ was associated with a better prognosis in both cohorts. Considering only strongly stained cells as positive, ALDH1A1+ was associated with oestrogen receptor and progesterone receptor negativity in both cohorts and worse prognosis in one of the cohorts. Stromal ALDH1A1 staining was associated with improved DDFS in one cohort. Gene expression analysis showed that a high ALDH1A1 expression was associated with a better prognosis.

Conclusions ALDH1A1 is associated with DDFS and clinicopathological variables, both in cancer cells and stroma, but is highly cut-off dependent. Only the strongly ALDH1A1-stained cells show a more aggressive phenotype typical for CSCs.

  • BREAST CANCER
  • CANCER STEM CELLS
  • ENZYMES
  • ONCOLOGY
  • TUMOUR MARKERS

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