Cytokeratin 7, GATA3, and SOX-10 is a Comprehensive Panel in Diagnosing Triple Negative Breast Cancer Brain Metastases

Abstract

Following lung cancer, breast cancer is the second most common metastatic tumor to the brain, of which triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2+ (HER2+) breast cancer are the most common subtypes. TNBC does not have standard immunoprofiles and can be difficult to distinguish from other metastases. A tissue microarray was created from 47 patients with breast cancer metastases to the brain and 12 paired breast primaries. Of 47 breast cancer metastases, 24 were HER2+, 14 were TNBC, and 9 were luminal. Forty-five were cytokeratin 7 (CK7) positive, 36 were GATA-binding protein 3 (GATA3) positive, 7 were Sry-related HMg-Box gene 10 (SOX-10) positive, 20 were mammaglobin positive, and 19 were gross cystic disease fluid protein 15 positive. At least one of the CK7, GATA3, or SOX-10 was positive in all TNBC metastases. A panel of CK7, GATA3, and SOX-10 is complementary in the diagnosis of breast cancer brain metastasis. SOX-10 appears to be a specific but not particularly sensitive marker in this context.

Differential Regulation of Lacto-/Neolacto- Glycosphingolipid Biosynthesis Pathway Reveals Transcription Factors as Potential Candidates in Triple-Negative Breast Cancer

“…GATA3 transcription factor has previously been associated with less aggressive ER+ BC [63], but recent studies reported the expression of GATA3 in a subset of TNBC, with a broad range of 31.4% to 83% of TNBCs reported in different studies [64][65][66]. Interestingly, GATA3 expression appears to correlate with TNBC metastasis [67], and GATA3 gene variants were detected in 11% of metastatic BCs in a 115 patient cohort [68]. However, there has been no established link between GATA3 expression and glycosylation regulation or GSL pathway.…”

Combination of GATA3, SOX-10, and PAX8 in a Comprehensive Panel to Diagnose Breast Cancer Metastases

“…Meanwhile, metastatic malignant melanoma can simulate a variety of high-grade tumors, including TNBC, suggesting that SOX10 expression may not help differentiate TNBC from malignant melanoma (20). Therefore, SOX10 expression levels in such scenarios should be interpreted in conjunction with other melanocyte markers, namely Human Melanoma Black (HMB) 45 and Melan-A, to avoid diagnostic pitfalls (7).…”

Avoiding “False Positive” and “False Negative” Immunohistochemical Results in Breast Pathology

“…SOX-10 has been emerging as a complementary marker to GATA3 in diagnosing metastatic breast cancer, es- pecially for TNBC [83][84][85]. One study found that 82% of TNBCs was GATA3 positive and 58% was SOX-10 positive, with 95% being positive for at least one marker [86].…”

“…Another study demonstrated that SOX-10 had sensitivity of 62.3% and specificity of 100% as a marker in favor of TNBC compared with lung adenocarcinoma, while GATA3 only had a moderate sensitivity of 30.4% and a specificity of 98.7% in TNBCs [87]. A recent study found that SOX-10 exhibited the greatest utility in diagnosing poorly differentiated, GATA3 negative TNBC cases as most SOX-10 positive TNBCs were GATA3 negative or focal/weak (5/6, 83.3%) [88].…”