title: Pregnancy-associated plasma protein-A expression in human  breast cancer.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Mansfield
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Visscher
authors.forename: Steven N
authors.initials: SN
authors.lastname: Hart
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Goetz
authors.forename: Claus
authors.initials: C
authors.lastname: Oxvig
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Conover
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human