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Updated: Apr 14, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
High Expression of PAPP-A Predicts Poor Outcomes in Oestrogen Receptor-Positive Breast Cancer Patients
Zeanap Mabruk1, Esme Bullock1, Xue Xiao2
1Cancer Research UK Scotland Centre (Edinburgh), Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, UK.
Introduction:
Insulin-like growth factor 1 (IGF-1)/IGF-1 receptor (IGF-1R) signalling is activated in breast cancer and associated with disease progression. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that can cleave IGF binding proteins leading to the release of bioactive IGF-1 and the subsequent activation of IGF-1 signalling. Here, we aimed to assess the prognostic significance of PAPP-A in breast cancer.
Methods:
Breast cancer tissue microarrays were stained for PAPP-A and expression correlated with survival and other clinical features. Analysis of publicly available data sets was carried out to determine associations between PAPPA and gene sets associated with IGF-1/IGF-1R pathway activation.
Results:
PAPP-A was expressed in both the tumour and stromal compartments in breast cancer specimens and was higher in oestrogen receptor (ER)-negative (ER-) than ER-positive (ER+) cases. There was a significant association between high PAPP-A expression and reduced cancer-specific survival (CSS) in ER+ (HR 1.389, 95% CI 1.051-1.836, p = 0.021) but not ER- patients (HR 1.040, 95% CI 0.712-1.598, p = 0.838). In a second cohort of ER+ invasive lobular carcinoma (ILC) PAPP-A expression was also associated with reduced CSS (HR 1.765, 95% CI 1.098-2.836, p = 0.019). PAPPA correlated with REACTOME PI3K-AKT and IGF1R signalling gene sets in ER+ breast cancers.
Conclusion:
High expression of PAPP-A is associated with poor prognosis in ER+ breast cancer and correlates with IGF-1/IGF-1R pathway activation.
