Researchers in the Johns Hopkins Division of Breast Pathology report that the transcription factor GATA3 is expressed more subsets of invasive breast carcinomas than previously known. In a study published online ahead of print in Human Pathology (http://www.ncbi.nlm.nih.gov/pubmed/23375642), researchers investigated the role of GATA3 in different types of primary and metastatic breast carcinomas, as well as stromal lesions. GATA3 is a protein that acts as a transcription factor, which means it controls the transcription (or “writing”) of DNA genes into RNA so that they can become proteins. GATA3 plays a role in the development of many different tissues types, including the breast, inflammatory T cells, and hair follicles. Immunohistochemistry for the GATA3 protein has been shown to be positive in certain breast carcinomas and in urothelial carcinomas. Although multiple studies previously showed GATA3 to be positive in estrogen and progesterone receptor (ER and PR)-positive carcinomas, this is the first study to look at GATA3 expression in breast carcinomas subdivided by the subtypes of ER and PR-positive/Her2-negative (“luminal type”), ER and PR-negative/Her2-positive (“Her2-positive type”), and ER/PR/Her2-negative (“triple negative”) including the specific subtype of metaplastic (sarcomatoid) breast carcinomas. Furthermore, this is the first study to look at GATA3 in matched primary and metastatic carcinomas from the same patient, as well as in the fibroepithelial (or “stromal”) lesions of phyllodes tumors and fibroadenomas.
In this study, our researchers found that GATA3 labeling was seen in 67% (66/99) of primary ductal carcinomas including 43% of triple-negative and 54% of metaplastic carcinomas. In the cases of paired primary and metastatic carcinomas, GATA3 labeling was seen in 90% (27/30) of primary breast carcinomas in the, including 67% of triple-negative carcinomas GATA3 labeling was overwhelmingly maintained in paired metastases, including all metastases which lost ER and/or PR expression from the primary. In contrast, GATA3 labeling was seen in only 1 fibroepithelial neoplasm (a phyllodes tumor), which suggests that GATA3 labeling may help distinguish metaplastic carcinoma from malignant phyllodes tumors. This research shows that GATA3 can be particularly useful as a marker for metastatic breast carcinoma, especially triple-negative and metaplastic carcinomas, which lack specific markers of mammary origin including ER.
Reference: Cimino-Mathews A, Subhawong AP, Illei PB, Sharma R, Halushka MK, Vang R, Fetting JH, Park BH, Argani PA. GATA-3 Expression in Breast Carcinoma: Utility in Triple Negative, Sarcomatoid and Metastatic Carcinomas. Human Pathol. 2013 Jan 31. [Epub ahead of print]