Differential expression of transferrin receptor (TfR) in a spectrum of normal to malignant breast tissues: implications for in situ and invasive carcinoma.

Transferrin receptor (TfR), a type II transmembranous receptor involved in iron uptake, is highly expressed in some cancers. We evaluated the expression of TfR in a spectrum of normal to malignant breast tissues to test the hypothesis that overexpression is associated with malignant transformation. Expression of TfR was studied by immunohistochemistry (CD71-Antibody, Thermo Fisher Scientific, Fremont, CA) for percent positive cells (%) and intensity of staining (0 to 3 score) in normal (n=127), benign (n=172), potentially premalignant and in-situ carcinoma (n=65), and invasive carcinoma (n=38). Normal and benign lesions had significantly lower TfR expression compared with premalignant lesions (atypical hyperplasia and carcinoma in situ) and invasive carcinoma (median %: 0, 10, 50, and 80, respectively; P<0.0001). TfR expression was higher in high-grade ductal carcinoma in situ (DCIS) than in other grades of DCIS (median %: 95 vs 55; P=0.02) and in high-grade invasive carcinoma. Among the latter, medullary carcinoma had the highest expression and there was a trend for invasive lobular carcinoma to have a higher expression than invasive ductal carcinoma. In invasive carcinoma cases, the proportion (%) of cells staining for TfR was inversely correlated with the percentage of estrogen receptor-positive cells, with a decreasing slope on linear regression models. In comparison, the relationship with progesterone receptor was not as well defined and linear regression models revealed close to a flat line. These data show that there is a differential expression of TfR in breast tissues with the highest expression in in-situ and invasive carcinoma and with aggressive phenotypes (higher grade DCIS and lower estrogen receptor positivity in invasive carcinomas). Further studies are indicated to determine whether TfR is an independently significant prognostic marker that may have potential as a therapeutic target in in-situ and invasive breast carcinoma.