April 2013 –GATA3 expression is detected in primary and metastatic breast carcinomas, including those which are triple negative for ER, PR and Her2

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]

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January 2013 – Resident research in breast cancer to be presented at upcoming pathology conference in Baltimore

The annual conference held by the United States & Canadian Academy of Pathology (USCAP) will be in Baltimore, March 2-8, 2013. This conference presents continuing education opportunities and is a forum for the presentation of cutting edge research and discoveries. Pathology residents from the Johns Hopkins Hospital are presenting their original research projects in many areas of disease, including breast cancer. Please help us congratulate these resident researchers on their accomplishment and contribution to the field of breast cancer research. These novel research projects in breast cancer with resident first authors include:

 NKX3.1 Expression in Primary Breast Carcinoma
Resident first author: Mark A Samols MD
Additional authors: Andrea Subhawong MD, Rajni Sharma PhD, Peter B Illei MD, Pedram Argani MD, Ashley Cimino-Mathews MD

Frozen Section Evaluation of Breast Carcinoma Sentinel Lymph Nodes: A Retrospective Review of 1940 Cases
Resident first author: Justin Poling, MD
Additional authors: Pedram Argani MD, Ashley Cimino-Mathews MD

Are Breast Cancer Metastases Enriched for Stem Cells?
Resident first author: Doreen Nguyen MD
Additional Authors: Andrea Subhawong MD, Celina Kleer MD, Pedram Argani MD, Ashley Cimino-Mathews MD

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December 2012 – The transcription factor Sox10 is expressed in invasive breast carcinomas

Researchers in the Johns Hopkins Division of Breast Pathology report that the transcription factor Sox10 is expressed in a subset of invasive breast carcinomas. In a study published online ahead of print in Human Pathology (http://www.ncbi.nlm.nih.gov/pubmed/23260325), researchers investigated the role of Sox10 in various subtypes of breast tumors. Sox10 is a transcription factor, which means that interacts it with DNA to cause the transcription (or “writing”) of certain genes from DNA into RNA to become proteins. It was previously thought that Sox10 was specific to cells derived from the neural crest, such as the melanocytes of normal skin and of the tumor melanoma, as well as the benign myoepithelial cells of the breast. In this study, our researchers found that 40% of breast carcinomas labeled for the Sox10 transcription factor by immunohistochemistry, and this expression which was seen primarily in aggressive subtypes of the basal-like, unclassified triple negative and metaplastic carcinomas. These findings show that breast carcinoma must be considered in the differential diagnosis of melanoma for a mestastatic malignant neoplasm that is positive for S100 and Sox10. Additionally, Sox10 expression in the basal-like, unclassified triple negative, and metaplastic carcinomas supports the concept that these neoplasms show myoepithelial (or basal-like) differentiation. This research suggests that potential treatments targeting the Sox10 pathway may be useful in the most aggressive types of breast carcinoma.

Reference: Cimino-Mathews A, Subhawong AP, Elwood H, Warzecha HN, Sharma R, Park BH, Taube JM, Illei PB, Argani P. Neural crest transcription factor Sox10 is preferentially expressed in triple-negative and metaplastic breast carcinomas. Hum Pathol. 2012 Dec 19.[Epub ahead of print].

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