A novel truncated form of S100P predicts disease-free survival in patients with lymph node positive breast cancer

• S100P occurs in breast tumor tissue predominantly in a 9.2-kDa carboxyterminally truncated form.
• Truncated S100P is exclusively found in the cell nucleus.
• Truncated S100P can be localized in tissue sections by imaging mass spectrometry.
• This novel S100P isoform is strongly prognostic for poor disease-free survival in women with node-positive breast cancer.

The calcium-binding protein S100P is overexpressed in various cancers and may contribute to the oncogenic phenotype. This study used mass spectrometry to characterize a novel 9.2-kDa C-terminally truncated form of S100P (t-S100P), and to investigate its potential prognostic value in breast cancer. Univariate analysis demonstrated the association between breast tissue t-S100P levels (n = 148) and conventional pathological markers. Across all tumor samples, high t-S100P was strongly prognostic for poor disease-free survival (P = 0.005), its efficacy confined to lymph node-positive tumors (n = 74, P = 0.007). Matrix-assisted laser desorption/ionization imaging mass spectrometry confirmed differential t-S100P abundance between breast cancer and unaffected adjacent tissue. t-S100P was exclusively located in the cell nucleus of breast cancer tissue, and full-length S100P was essentially undetectable by mass spectrometry. We conclude that t-S100P is the predominant form of S100P in breast cancer tissue and is strongly prognostic for disease-free survival in women with lymph node-positive disease.