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

Abstract

ObjectivePregnancy-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. ResultsPAPP-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). ConclusionPAPP-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.