Mansfield Aaron S, Visscher Daniel W, Hart Steven N, Wang Chen, Goetz Matthew P, Oxvig Claus, Conover Cheryl A
Growth Horm IGF Res. 2014 Dec;24(6):264-7. doi: 10.1016/j.ghir.2014.10.007.
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.
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).
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.
妊娠相关血浆蛋白-A（PAPP-A）是胰岛素样生长因子系统中的一种锌金属蛋白酶，由非妊娠组织表达，参与正常生长和生长失调过程。PAPP-A与多种癌症有关。然而，关于PAPP-A在乳腺癌中表达的研究有限。在本研究中，我们评估了PAPP-A在人类恶性乳腺癌不同亚型中的表达情况。设计：将46例浸润性乳腺癌女性患者的福尔马林固定石蜡包埋肿瘤样本分为五个明确的组[使用HER2、雌激素受体、孕激素受体、增殖标志物]，这些组大致与分子定义的亚型（腔面A型、腔面B型、腔面/HER2+型、HER2+型、三阴性）相关。通过免疫组织化学分析这些样本中PAPP-A的表达。
46个标本中有45个在肿瘤组织中检测到PAPP-A染色。增殖指数高的腔面B型标本中PAPP-A表达的范围和强度明显大于腔面A型标本（P = 0.01）。然而，HER2阳性或阴性标本之间（P = 0.14）以及雌激素受体阳性和阴性标本之间（P = 0.31）没有差异。
几乎所有乳腺癌标本中都检测到了PAPP-A，与腔面A型标本相比，腔面B型标本中其表达更强烈且范围更广。PAPP-A在乳腺癌预后以及可能的治疗中的作用值得进一步研究。
