hyperplasia (ADH), atypical lobular hyperplasia (ALH), ductal carcinoma in situ ... included other common benign lesions such as sclerosing adenosis and ...
RESEARCH ARTICLE
Differential Expression of Transferrin Receptor (TfR) in a Spectrum of Normal to Malignant Breast Tissues: Implications for In Situ and Invasive Carcinoma Meenakshi Singh, MD,* Kimberly Mugler, MD,w Dulan W. Hailoo, MD,* Stephanie Burke, BS,* Barbara Nemesure, PhD,w Kathleen Torkko, PhD,z and Kenneth R. Shroyer, MD, PhD*
Abstract: 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; P60% cases) with the median staining intensity for all lesions in group 1 being 1 (Table 1; Fig. 3).
TfR Protein Expression in Atypical Hyperplasia and In-situ Carcinoma (Group 2) All diagnostic categories within group 2 (ADH, DCIS, ALH, and LCIS) revealed TfR expression (Table 1). The median proportion of positive staining cells in group 2 was 50%. A greater median proportion of staining was found in LCIS (90%) and DCIS (85%), whereas a lesser median proportion of staining was found in ALH (0%) and ADH (5%) (Table 1). The median staining intensity for DCIS and LCIS was also higher than that in atypical hyperplasias (2 vs 1or 0) (Table 1). TfR expression was greater in high-grade DCIS compared with lower grades of DCIS (median percent positive cells: 95 vs 55; P = 0.02) (Figs. 1, 2). The difference in the median proportion of cells staining for and the staining intensity for TfR in group 2 versus group 1 was statistically significant (P
