title: Expression of cancer-associated fibroblast-related proteins differs between invasive lobular carcinoma and invasive ductal carcinoma.
abstract: Cancer-associated fibroblasts (CAFs) are classified into various functional subtypes such as fibroblast activation protein-α (FAP-α), fibroblast specific protein-1 (FSP-1), platelet-derived growth factor receptor-α (PDGFR-α), and PDGFR-β. In this study, we compared the expression of CAF-related proteins in invasive lobular carcinoma (ILC) with those in invasive carcinoma of no special type (NST) and assessed the implications of the differences observed. Using tissue microarrays of 104 ILC and 524 invasive carcinoma (NST) cases, immunohistochemistry for CAF-related proteins [podoplanin, prolyl 4-hydroxylase, FAP-α, FSP-1/S100A4, PDGFR-α, PDGFR-β, and chondroitin sulfate proteoglycan (NG2)] was conducted. In invasive carcinoma (NST), tumor cells expressed a high level of PDGFR-α, whereas ILC tumor cells expressed high levels of podoplanin, prolyl 4-hydroxylase, FAP-α, and FSP-1/S100A4. In stromal cells of invasive carcinoma (NST), high expression levels of prolyl 4-hydroxylase, PDGFR-α, and NG2 were observed, whereas ILC stromal cells expressed high levels of FAP-α, FSP-1/S100A4, and PDGFR-β. In ILC, tumoral FSP-1/S100A4 positivity was associated with higher Ki-67 labeling index (p = 0.010) and non-luminal A type cancer (p = 0.014). Stromal PDGFR-α positivity was associated with lymph node metastasis (p = 0.011). On survival analysis of entire cases, tumoral FSP-1/S100A4 positivity (p = 0.002), stromal podoplanin positivity (p = 0.041), and stromal FSP-1/S100A4 negativity (p = 0.041) were associated with shorter disease-free survival; only tumoral FSP-1/S100A4 positivity (p = 0.044) was associated with shorter overall survival. In ILC, the expression of FAP-α and FSP-1/S100A4 was higher in both tumor and stromal cells than that observed in invasive carcinoma (NST). These results indicate that CAFs are a potential target in ILC treatment.
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.
authors.forename: Cheol Keun
authors.initials: CK
authors.lastname: Park
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.
authors.forename: Woo Hee
authors.initials: WH
authors.lastname: Jung
authors.affiliation: Department of Pathology, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea. kjs1976@yuhs.ac.
authors.forename: Ja Seung
authors.initials: JS
authors.lastname: Koo
mesh_terms: D000941:Antigens / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology*; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D064828:Prolyl Hydroxylases / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4 / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D046888:Tissue Array Analysis; D000099216:Chondroitin Sulfate Proteoglycan 4; D000099167:Fibroblast Activation Protein Alpha; D000098853:Podoplanin
chemical_list: D000941:Antigens; D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D064828:Prolyl Hydroxylases; D011509:Proteoglycans; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D000071999:S100 Calcium-Binding Protein A4; D012697:Serine Endopeptidases; D000099216:Chondroitin Sulfate Proteoglycan 4; D000099167:Fibroblast Activation Protein Alpha; C117468:PDPN protein, human; D000098853:Podoplanin; C077591:S100A4 protein, human; C000605860:PDGFRB protein, human
keywords: Breast cancer; Cancer-associated fibroblast; Invasive ductal carcinoma; Invasive lobular carcinoma; Tumor stroma