Pregnancy-associated plasma protein-A expression in human breast cancer

Growth Horm IGF Res. 2014 Dec;24(6):264-7. doi: 10.1016/j.ghir.2014.10.007.


Objective: Pregnancy-associated plasma protein-A (PAPP-A) is a zinc metalloproteinase in the insulin-like growth factor system that is expressed by tissues outside of pregnancy and involved in normal and dysregulated growth. PAPP-A has been implicated in several cancers. However, studies of PAPP-A expression in breast cancer are limited. In this study, we assessed PAPP-A expression in different subtypes of human malignant breast cancer. Design Formalin-fixed paraffin-embedded tumor samples from 46 female patients with invasive breast cancer were divided into five defined groups [using markers for HER2, estrogen receptor, progesterone receptor, proliferation] that roughly correlate with molecularly defined subtypes (luminal A, luminal B, luminal/HER2 +, HER2 +, triple negative). These samples were analyzed for PAPP-A expression by immunohistochemistry.

Results: PAPP-A staining in tumor tissue was detected in 45 of 46 specimens. There were significantly greater extent and intensity of PAPP-A expression in luminal B specimens with high proliferation index than luminal A specimens (P = 0.01). However, there were no differences between specimens positive or negative for HER2 (P = 0.14) or positive and negative for estrogen receptor (P = 0.31).

Conclusion: PAPP-A was detected in almost all breast cancer specimens and a more intense and greater extent of its expression was associated with luminal B specimens compared to luminal A specimens. The role of PAPP-A in breast cancer prognosis, and possibly therapeutics, warrants further investigation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Lobular / metabolism*
  • Carcinoma, Lobular / pathology
  • Estrogen Receptor alpha / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Pregnancy
  • Pregnancy-Associated Plasma Protein-A / metabolism*
  • Prognosis
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism


  • Biomarkers, Tumor
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Pregnancy-Associated Plasma Protein-A
  • PAPPA protein, human