Expression of cytokeratin markers, ER-alpha, PR, HER-2/neu, and EGFR in pure ductal carcinoma in situ (DCIS) and DCIS with co-existing invasive ductal carcinoma (IDC) of the breast.
Previously, we showed that pure ductal carcinoma in situ (DCIS) of the breast can be divided into 3 subtypes (luminal, basal/stem, and null) based on the expression of 5 cytokeratin (CK) markers: CK5/6, CK14, CK17 (stem/basal), and CK8, CK18 (luminal). The distributions of CK subtypes were associated with nuclear grade and differential expression of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), HER-2/neu, and epidermal growth factor receptor (EGFR). In this study, we further explore the expression patterns of CK markers, ER-alpha, PR, HER-2/neu, and EGFR by immunohistochemical (IHC) analysis of 99 cases of pure DCIS and 96 cases of DCIS with co-existing invasive ductal carcinoma (DCIS/IDC). We show that between high-grade DCIS and DCIS/IDC, there are differential expression patterns for ER-alpha, PR, and EGFR in corresponding CK subtypes, suggesting that at least some pure DCIS is molecularly distinct from DCIS/IDC. In most cases there is a high degree of co-expression of these markers between DCIS and the co-existing IDC, suggesting that DCIS is frequently a precursor lesion for co-existing IDC. The rate of discordant expression of these markers is low and is more frequently associated with high-grade carcinoma, suggesting that other molecular pathways also may also be present. There are significant differences in the expression of these molecular markers between high-grade and non-high-grade carcinomas, supporting the view that high-grade and non-high-grade carcinomas of the breast are molecularly distinct entities.
Steinman
Sharon
S
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Wang
Jianmin
J
Bourne
Patricia
P
Yang
Qi
Q
Tang
Ping
P
D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D009378:Neoplasms, Multiple Primary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D047628:Estrogen Receptor alpha; D007633:Keratins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone