Differential Expression of Cancer-Associated Fibroblast-Related Proteins in Ductal Carcinoma in situ According to Molecular Subtype and Stromal Histology

Abstract

OBJECTIVE: The purpose of this study is to investigate the expression of cancer-associated fibroblast (CAF)-related proteins and their implication in ductal carcinoma in situ (DCIS).

METHODS: We constructed a tissue microarray of 223 cases of DCIS and examined immunohistochemical staining for the 7 CAF-related proteins. We classified DCIS into luminal type, human epidermal growth factor receptor-2 (HER-2) type, and triple negative breast cancer (TNBC) according to the immunohistochemical results for estrogen receptor, progesterone receptor, and HER-2. We also classified DCIS into desmoplastic, normal-like, and inflammatory type according to stromal histology.

RESULTS: There were significant differences in the expression of S100A4, podoplanin, prolyl 4-hydroxylase subunit alpha 3, NG2, and PDGFRα in stromal cells of DCIS when classified according to molecular subtype. The expression rate of all CAF-related proteins in stromal cells was higher in the HER-2 type and TNBC than in the luminal type (p < 0.001). When classified according to stromal subtype, there were significant differences in the expression of all CAF-related proteins in stromal cells, with the inflammatory stromal type showing higher expression of CAF-related proteins than other stromal types.

CONCLUSION: The expression of CAF-related proteins in stromal cells of DCIS varies according to molecular subtype and stromal type.