title: Identification and characterization of optimal gene expression markers for detection of breast cancer metastasis.
abstract: Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement in breast cancer. Historically, SLN-positive patients have undergone axillary lymph node dissection in a second surgery. Intraoperative SLN analysis could reduce the cost and complications of a second surgery; however, existing histopathological methods lack standardization and exhibit poor sensitivity. Rapid molecular methods may lead to improved intraoperative diagnosis of SLN metastasis. In this study, we used a genome-wide gene expression analysis of breast and other tissues to identify seven putative markers for detecting breast cancer metastasis. We assessed the utility of these markers for identifying clinically actionable metastases in lymph nodes through reverse transcriptase-polymerase chain reaction analysis of SLNs from 254 breast cancer patients. Polymerase chain reaction signals were compared to pathology on a per-patient basis. The optimal two-gene combination, mammaglobin and cytokeratin 19, detected clinically actionable metastasis in breast SLNs with 90% sensitivity and 94% specificity. Application of stringent criteria for identifying presumptive hematoxylin- and eosin-positive samples increased sensitivity and specificity to 91 and 97%, respectively. This study represents the first comprehensive demonstration of the utility of gene expression markers for detecting clinically actionable breast metastases. An intraoperative molecular assay using these markers has the potential to significantly reduce second surgeries for patients undergoing SLN dissection.
authors.affiliation: Veridex, LLC, P.O. Box 4920, 33 Technology Drive, Warren, NJ 07059, USA. jbackus@vrxus.jnj.com
authors.forename: John
authors.initials: J
authors.lastname: Backus
authors.forename: Todd
authors.initials: T
authors.lastname: Laughlin
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Belly
authors.forename: Robert
authors.initials: R
authors.lastname: White
authors.forename: Jon
authors.initials: J
authors.lastname: Baden
authors.forename: C
authors.initials: C
authors.lastname: Justus Min
authors.forename: Ann
authors.initials: A
authors.lastname: Mannie
authors.forename: Lorraine
authors.initials: L
authors.lastname: Tafra
authors.forename: David
authors.initials: D
authors.lastname: Atkins
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Verbanac
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000556:secondary*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm