title: Periostin expression in cancer-associated fibroblasts of invasive ductal breast carcinoma.
abstract: Periostin (POSTN) is a secreted cell adhesion glycoprotein that plays an important role in proliferation, adhesion and migration processes, as well as in regulation of mechanisms related to epithelial-mesenchymal transition (EMT). It also plays a key role in angio- and lymphangiogenesis and in formation of distant metastases. The aim of this work was to determine expression of POSTN in invasive ductal breast carcinoma (IDC) and in non-invasive ductal carcinoma in situ (DCIS) and to correlate its expression with clinicopathological parameters. Material for immunohistochemical studies (IHC) comprise of 70 IDC cases, 44 DCIS cases and 21 cases of fibrocystic change (FC). Frozen (-80˚C) fragments of tumours taken from 41 patients with IDC were used for molecular studies (real-time PCR), including 11 cases of IDC subjected to laser capture microdissection (LCM). POSTN expression was shown mainly in tumour stromal cells, i.e. cancer-associated fibroblasts (CAFs). Statistically significant higher level of POSTN expression in CAFs in IDC as compared to FC (p<0.0001) was observed. Additionally, statistically elevated expression level of POSTN in CAFs in IDC relative to DCIS (p<0.0001) and significantly increased expression of POSTN in CAFs in DCIS in comparison to FC (p=0.0158) was also shown. High level of POSTN expression in CAFs in IDC (>8 IRS points) was significantly correlated with tumour malignancy grade (G) (p=0.0070). Moreover, higher POSTN expression by CAFs was associated with patient shorter overall survival. Significant increase of POSTN expression on mRNA and protein level in CAFs in IDC with the growing malignancy grade of the tumours (G) was shown. Furthermore, with the use of LCM method, statistically significant higher expression of mRNA POSTN in stromal cells relative to cancer cells (p<0.001) was noted. POSTN might be a factor playing an important role in the mechanism of IDC progression.
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Ratajczak-Wielgomas
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland.
authors.forename: Jedrzej
authors.initials: J
authors.lastname: Grzegrzolka
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Piotrowska
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gomulkiewicz
authors.affiliation: Regional Specialist Hospital, Research and Development Center, 51-124 Wroclaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Witkiewicz
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Dziegiel
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human