Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast
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Zoran Gatalica1, Semir Vranic2, Anatole Ghazalpour1, Joanne Xiu1, Idris Tolgay Ocal3, John McGill4, Ryan P. Bender1, Erin Discianno1, Aaron Schlum1, Souzan Sanati5, Juan Palazzo6, Sandeep Reddy1, Barbara Pockaj3
1Caris Life Sciences, Phoenix, AZ, United States of America
2Department of Pathology, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina
3Mayo Clinic, Scottsdale, AZ, United States of America
4Miraca Life Sciences, Phoenix, AZ, United States of America
5Division of Anatomic and Molecular Pathology, Washington University School of Medicine, Saint Louis, MO, United States of America
6Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Philadelphia, PA, United States of America
Zoran Gatalica, e-mail: email@example.com
Keywords: breast, fibroepithelial tumors, malignant phyllodes tumor, biomarkers, molecular profiling
Received: November 04, 2015 Accepted: November 17, 2015 Published: November 28, 2015
Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast.
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