title: X-Ray of Excised Cancerous Breast Tissue Does Not Affect Clinical Biomarker Expression.
abstract: College of American Pathologists (CAP) and the American Society of Clinical Oncology have emphasized the need to reduce preanalytic variables for evaluating predictive biomarker expression in breast cancer. Postoperative x-ray of excised breast tissue is commonplace, yet is a variable that has not been investigated previously. We asked whether such radiation affects expression of relevant biomarkers.
  
  
  
  A previous study found that human breast cancers grown in mice demonstrate the same immunohistochemical and molecular profiles as the original tumors. Thirteen patient-derived xenografts were harvested fresh and divided for specimen radiography and a matched nonirradiated control, while following CAP/ASCO guidelines for cold ischemia time and fixation. Samples were processed in a tissue microarray for immunohistochemistry. Estrogen receptor (ER), progesterone receptor (PR), p53, and Ki67 staining was evaluated using an optimized scoring algorithm performed on digitally scanned slides. Samples were also scored manually by a blinded pathologist using the H-score method, and HER2 by the CAP/ASCO 2013 protocol. Histologic scores were compared by analysis of variance.
  
  
  
  There was no significant difference in quantity or intensity of staining between irradiated and nonirradiated samples for estrogen receptor (P=0.28), p53 (P=0.96), and Ki67 (P=0.94). A small but statistically significant difference was observed for PR (P=0.0058). HER2 staining was similarly unchanged in the 1 tumor exhibiting 3+ staining.
  
  
  
  Our study demonstrates that x-ray of breast carcinomas does not significantly affect the expression of predictive biomarkers, with the exception of PR for unclear reasons. It also highlights the utility of the patient-derived xenograft model for biomarker studies.
authors.affiliation: Departments of Pathology.
authors.forename: Isaac E
authors.initials: IE
authors.lastname: Lloyd
authors.affiliation: Oncological Sciences, Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Alana L
authors.initials: AL
authors.lastname: Welm
authors.affiliation: Oncological Sciences, Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Yoko
authors.initials: Y
authors.lastname: DeRose
authors.affiliation: Surgery, University of Utah.|Department of Surgery, University of Arizona College of Medicine Tucson and University of Arizona Cancer Center, Tucson, AZ.
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Neumayer
authors.affiliation: ARUP Laboratories, Salt Lake City, UT.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Kohan
authors.affiliation: ARUP Laboratories, Salt Lake City, UT.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Malmberg
authors.affiliation: ARUP Laboratories, Salt Lake City, UT.
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Salama
authors.affiliation: Departments of Pathology.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Factor
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D014965:X-Rays
chemical_list: D014408:Biomarkers, Tumor