PMID- 36635351 OWN - NLM STAT- MEDLINE DCOM- 20230116 LR - 20230301 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 13 IP - 1 DP - 2023 Jan 12 TI - PDJ amplicon in triple negative breast cancer. PG - 618 LID - 10.1038/s41598-023-27887-8 [doi] LID - 618 AB - Amplification of chromosome 9p24.1 targeting PD-L1, PD-L2, and JAK2 (PDJ amplicon) is present in subsets of triple negative breast cancers (TNBCs) and is associated with poor clinical outcomes. However, the prevalence of PDJ+ TNBCs varies extensively across studies applying different methods for interrogating samples of interest. To rigorously assess the prevalence of PDJ amplicons in TNBC, its prognostic value and whether it is enriched by chemotherapy, we interrogated 360 TNBC samples including 74 surgical resections from patients treated in the neoadjuvant setting, and tissue microarrays (TMAs) with 31 cases from African American women and 255 resected non-metastatic cases, with a 3 color fluorescence in situ hybridization (FISH) assay targeting the 9p24.1 PDJ amplicon, 9q24.3, and 9q34.1. Samples with mean PDJ signal of > 4.5 copies, and ratios of PDJ/9q24 >/= 2 and/or PDJ/9q34.1 >/= 2 were called amplified (PDJ+). Correlative analyses included the association of tumor infiltrating lymphocytes (TILs) with PDJ amplicons in TNBCs. In addition, we investigated intratumor copy number of PDJ amplicons in PDJ+ and PDJ- TNBCs. Matched pre- and post-neoadjuvant treatment biopsies were available from patients (n = 6) to evaluate the effects of therapy on PDJ status. Our study provides a rigorous analysis of the prevalence, distribution, and clinical correlatives of the PDJ amplicon in TNBC. CI - (c) 2023. The Author(s). FAU - Roesler, Alexander S AU - Roesler AS AD - Department of Research, Mayo Clinic in Arizona, Scottsdale, AZ, USA. AD - School of Medicine, Duke University, Durham, NC, USA. FAU - Malasi, Smriti AU - Malasi S AD - Department of Research, Mayo Clinic in Arizona, Scottsdale, AZ, USA. FAU - Koslosky, Lori AU - Koslosky L AD - MetaSystems Group, Inc., Newton, MA, USA. FAU - Hartmayer, Peter AU - Hartmayer P AD - MetaSystems Group, Inc., Newton, MA, USA. FAU - Naab, Tammey J AU - Naab TJ AD - Department of Pathology, Howard University Hospital, Washington, DC, USA. FAU - Carter, Jodi M AU - Carter JM AD - Departments of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. AD - Departments of Surgery, Mayo Clinic, Rochester, MN, USA. FAU - Zahrieh, David AU - Zahrieh D AD - Departments of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. FAU - Hillman, David AU - Hillman D AD - Departments of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. FAU - Leon-Ferre, Roberto A AU - Leon-Ferre RA AD - Departments of Oncology, Mayo Clinic, Rochester, MN, USA. FAU - Couch, Fergus J AU - Couch FJ AD - Departments of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. FAU - Goetz, Matthew P AU - Goetz MP AD - Departments of Oncology, Mayo Clinic, Rochester, MN, USA. FAU - Anderson, Karen S AU - Anderson KS AD - Division of Hematology-Oncology, Mayo Clinic in Arizona, Scottsdale, AZ, USA. AD - Biodesign Institute, Arizona State University, Tempe, AZ, USA. FAU - Pockaj, Barbara A AU - Pockaj BA AD - Division of General Surgery, Section of Surgical Oncology, Mayo Clinic in Arizona, Phoenix, AZ, USA. FAU - Barrett, Michael T AU - Barrett MT AD - Department of Research, Mayo Clinic in Arizona, Scottsdale, AZ, USA. barrett.michael@mayo.edu. AD - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic in Arizona, Scottsdale, AZ, USA. barrett.michael@mayo.edu. LA - eng GR - P50 CA116201/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230112 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (B7-H1 Antigen) RN - 0 (Biomarkers, Tumor) SB - IM MH - Humans MH - Female MH - *Triple Negative Breast Neoplasms/pathology MH - In Situ Hybridization, Fluorescence MH - Prognosis MH - B7-H1 Antigen/genetics MH - Neoadjuvant Therapy MH - Lymphocytes, Tumor-Infiltrating/pathology MH - Biomarkers, Tumor/genetics PMC - PMC9837184 COIS- Author LK. and P.H. are employed by MetaSystems Group, Inc. (Newton, MA, USA), and Author A.S.R., S.M., T.J.N., J.M.C.,D.Z., D.H., R.L.F., F.J.C., M.P.G., K.S.A., B.A.P., and M.B. do not have any Competing-Interest. EDAT- 2023/01/13 06:00 MHDA- 2023/01/17 06:00 PMCR- 2023/01/12 CRDT- 2023/01/12 23:18 PHST- 2022/09/12 00:00 [received] PHST- 2023/01/10 00:00 [accepted] PHST- 2023/01/12 23:18 [entrez] PHST- 2023/01/13 06:00 [pubmed] PHST- 2023/01/17 06:00 [medline] PHST- 2023/01/12 00:00 [pmc-release] AID - 10.1038/s41598-023-27887-8 [pii] AID - 27887 [pii] AID - 10.1038/s41598-023-27887-8 [doi] PST - epublish SO - Sci Rep. 2023 Jan 12;13(1):618. doi: 10.1038/s41598-023-27887-8.