Differential S100 Protein Family Expression in the Basal-Like Breast Carcinoma Subtype.
Kamaljeet Singh, Shaolei Lu, Harleen Sidhu, Lolie Noble, Rose Tavares, Ronald DeLellis, Murray Resnick, Evgeny Yakirevich. Rhode Island Hospital/Alpert Medical School of Brown University, Providence
Background: The S100 proteins are a calcium-binding family of proteins comprising 20 known members. Altered expression of S100 proteins has been described in breast, lung, bladder, kidney, thyroid, gastric, prostate and oral cancers. S100 proteins are commonly up-regulated in tumors and this is often associated with tumor progression. S100A2 and S100A9 have been documented as tumor suppressors in some cancers and as tumor promoters in others. Our aim was to investigate the expression pattern of S100, S100A2, S100A4, S100A6, and S100A9 in the different molecular subtypes of breast carcinoma.
Design: Tissue microarrays were constructed from 254 cases of grade 3 breast carcinoma. The cases were stratified into 3 subtypes based on expression of ER, HER2, CK5/6 and EGFR: 1) luminal (ER+), 2) HER2 (HER2+/ER-), and 3) basal-like (ER-/HER2-/CK5/6+ and /or EGFR+). Immunohistochemical expression of S100, S100A2, S100A4, S100A6 and S100A9 proteins was assessed in tumor cells and peritumoral stroma on a scale of 0-3+.
Results: The cases were stratified into 72 luminal, 70 HER2+ and 112 basal-like. Normal breast myoepithelial cells exhibited nuclear and cytoplasmic S100 staining. Normal luminal epithelium showed nuclear S100A2 and nuclear and cytoplasmic S100A6 expression. S100A4 and S100A9 were expressed in tumor cells, immune cells and the stromal cells but were absent in normal breast. Tumor cells showed both nuclear and cytoplasmic localization of all S100 proteins. The S100, S100A2, and S100A4 expression in tumor cells was significantly higher in basal-like subtype as opposed to ER+ and HER2+ tumors (P<0.0001). Expression of S100A6 and S100A9 proteins was significantly lower in the HER2 subtype as compared to the basal-like and luminal subtypes (P<0.0001). Expression of all S100 proteins in the tumor cells showed strong association with CK5/6 and EGFR expression (p<0.001).
|S100+ (%)||S100A2+ (%)||S100A4+ (%)||S100A6+ (%)||S100A9+ (%)|
|ER+||26 (38)||34 (50)||44 (69)||55 (83)||43 (69)|
|HER2||25 (40)||33 (52)||46 (73)||45 (73) **||19 (32) **|
|Basal||77 (77) *||73 (72) *||89 (89) *||84 (81)||71 (74)|