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Diagnostic Biomarkers in Metastatic Breast Cancer

Explore the role of GATA-3, GCDFP-15, and Mammaglobin as sensitive markers in diagnosing metastatic breast cancer. This study delves into the significance of these biomarkers in distinguishing breast cancer from other primary and metastatic tumors. Discover the implications of utilizing a panel of stains for enhanced diagnostic accuracy and the nuances of marker combinations in determining tissue origin. The findings shed light on the moderate sensitivity of these markers in triple-negative breast cancer, emphasizing the importance of comprehensive evaluation.

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Diagnostic Biomarkers in Metastatic Breast Cancer

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  1. Diagnostic Biomarkers in Metastatic Breast Cancer Lei Huo MD PhD The University of Texas MD Anderson Cancer Center

  2. Metastatic breast cancer • Unknown primary • Metastatic tumors to breast: • Melanoma • Carcinoma: ovary, lung, GI, kidney, skin (squamous) • (Lymphoma)

  3. Ovarian carcinoma WT1 PAX8 Breast carcinoma GCDFP-15 mammaglogin GATA-3 Lung adenocarcinoma TTF-1 Naspin A Renal cell carcinoma PAX8 PAX2 Pancreas (DPC4/SMAD4) Stomach Cholangiocarcinoma ER/PR+ ER/PR– Urothelial carcinoma GATA-3, uroplakin III Colon CDX2 +/– Ovarian mucinous carcinoma (ER, PAX8) –/+ +/+ CK7/CK20 Pancreas (DPC4/SMAD4) Stomach Cholangiocarcinoma –/– Stomach (CDX2) Breast carcinoma ER/PR, GCPFP-15, mammaglobin, GATA-3 Melanoma cocktail S100 melanA HMB-45 MiTF SOX10 Hepatocellular Carcinoma HepPar 1

  4. Sensitivity in breast cancer: GCDFP-15: 60% Mammaglobin: 80% GATA-3: 70-80%

  5. Primary TN (n=63) Metastatic TN (n=118) Huo L et al. Histopathology 2013

  6. 62 primary TNBC (all resection specimens) • 68 metastatic TNBC (44 biopsies, 24 excision specimens) Regional lymph nodes 19 Lung 25 Liver 9 Bone 4 Soft tissue 3 Ovary 2 GI tract 2 Distant LN 1 Bladder 1 Trachea 1 Uterus 1 Huo L et al. Histopathology 2015

  7. Antibodies • GCDFP-15: clone D6, Covance • Mammaglobin: clone 1A5, Biocare Medical • GATA-3: clone HG3-31, Santa Cruz Biotechnology Positivity • Positive: >5% • Focal: 5% or less • Negative: no staining

  8. Primary TN Huo L et al. Histopathology 2015

  9. Primary TN (n=62)

  10. GATA-3

  11. Metastatic TN (n=68)

  12. GCDFP-15 mammaglobin GATA-3

  13. GATA-3 is a more sensitive marker than GCDFP-15 and mammaglobin in TNBC • A panel of stains including all three markers may increase the diagnostic accuracy for tissue origin • The sensitivity in TNBC is moderate even when all three markers are combined, therefore negative staining for all markers does not exclude breast origin

  14. Acknowledgements Michael Deavers Michael Gilcrease Yun Gong Ming Guo Kelly Hunt Erika Resetkova Yun Wu Amy Zhang Jinxia Zhang Hui Chen Herminia Patino Ariana Trevino Kim-Anh Vu

  15. Thank you

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