Progranulin expression in breast cancer with different intrinsic subtypes

Abstract

Progranulin is a newly discovered 88-kDa glycoprotein originally purified from the highly tumorigenic mouse teratoma-derived cell line PC. We found that high progranulin expression was associated with higher breast carcinoma angiogenesis, reflected by increased vascular endothelial growth factor expression and higher microvessel density. However, no immunohistochemical evidence currently exists to correlate progranulin expression with clinicopathological features in different intrinsic subtypes of breast carcinoma biopsies. The aim of this study was to investigate the progranulin expression profiles in the intrinsic subtypes of breast carcinomas and their relevance to histopathological and clinicopathological features.Tissue blocks containing 264 cases of breast carcinomas from 2006 to 2009 were classified as different intrinsic subtypes. Tissues of four intrinsic subtypes were immunostained for progranulin, vascular endothelial growth factor and CD105. Their relevance to histopathological and clinicopathological features was also analyzed. Twenty tissue samples from breast fibroadenomas were included in this study.Progranulin expression showed no significant differences in different intrinsic subtypes, although an increasing tendency could be found in the triple-negative breast cancer (TNBC) subgroup (χ2=5.00, df=3, p=0.17). However, differences were significant when pathologically node metastasis-positive (pN+) TNBC were excluded (χ2=17.84, df=3, p<0.01). Some clinicopathological parameters, including CK5/6 (χ2=0.08, df=3, p=0.78), E-cadherin (χ2=0.71, df=3, p=0.40) and P53 (χ2=0.05, df=3, p=0.83), displayed no correlation with activity of progranulin in pathologically node metastasis-negative (pN−) TNBC. It was noted that the EGFR expression level of the pN− TNBC subtype was significantly higher in cases with strong progranulin expression than in cases with weak progranulin expression (χ2=11.26, df=1, p<0.01).A significantly higher expression level of progranulin in pN− TNBC suggests that progranulin is a promising new target for pN− TNBC treatment. Strong expression of progranulin correlates with positive EGFR expression in the pN− TNBC subtype. The close relationship between EGFR and progranulin/VEGF/CD105 expression may partly play a role in high angiogenesis levels in the pN− TNBC subtype.