ADAM8 is expressed widely in breast cancer and predicts poor outcome in hormone receptor positive, HER-2 negative patients

Cancer Cell International

Research

Sandra Althouse¹  Sha Cao¹  Steven J. Michael²  Nora D. Mineva³  Stefania Pianetti³  Gail E. Sonenshein³  Hannah H. Chen⁴  Kathy D. Miller⁵ 

[1] Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA;Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, 136 Harrison Ave., 02111, Boston, MA, USA;Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, 136 Harrison Ave., 02111, Boston, MA, USA;Adecto Pharmaceuticals, Inc., 75 Kneeland St., 14th Floor, 02111, Boston, MA, USA;Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, USA;Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, USA;

关键词: ADAM8;    Breast cancer;    Biomarker;    Immunohistochemistry;    Diagnosis;    Prognosis;   

DOI  :  10.1186/s12935-023-03024-3

 received in 2023-06-13, accepted in 2023-08-06,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundBreast malignancies are the predominant cancer-related cause of death in women. New methods of diagnosis, prognosis and treatment are necessary. Previously, we identified the breast cancer cell surface protein ADAM8 as a marker of poor survival, and a driver of Triple-Negative Breast Cancer (TNBC) growth and spread. Immunohistochemistry (IHC) with a research-only anti-ADAM8 antibody revealed 34.0% of TNBCs (17/50) expressed ADAM8. To identify those patients who could benefit from future ADAM8-based interventions, new clinical tests are needed. Here, we report on the preclinical development of a highly specific IHC assay for detection of ADAM8-positive breast tumors.MethodsFormalin-fixed paraffin-embedded sections of ADAM8-positive breast cell lines and patient-derived xenograft tumors were used in IHC to identify a lead antibody, appropriate staining conditions and controls. Patient breast cancer samples (n = 490) were used to validate the assay. Cox proportional hazards models assessed association between survival and ADAM8 expression.ResultsADAM8 staining conditions were optimized, a lead anti-human ADAM8 monoclonal IHC antibody (ADP2) identified, and a breast staining/scoring control cell line microarray (CCM) generated expressing a range of ADAM8 levels. Assay specificity, reproducibility, and appropriateness of the CCM for scoring tumor samples were demonstrated. Consistent with earlier findings, 36.1% (22/61) of patient TNBCs expressed ADAM8. Overall, 33.9% (166/490) of the breast cancer population was ADAM8-positive, including Hormone Receptor (HR) and Human Epidermal Growth Factor Receptor-2 (HER2) positive cancers, which were tested for the first time. For the most prevalent HR-positive/HER2-negative subtype, high ADAM8 expression identified patients at risk of poor survival.ConclusionsOur studies show ADAM8 is widely expressed in breast cancer and provide support for both a diagnostic and prognostic value of the ADP2 IHC assay. As ADAM8 has been implicated in multiple solid malignancies, continued development of this assay may have broad impact on cancer management.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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Fig. 2