title: Evaluation of BrightGen HR RT-qDx assay to detect nuclear receptors mRNA overexpression in FFPE breast cancer tissue samples for selection of tamoxifen therapy.
abstract: Breast cancer is a significant cause of death in women. Estrogen receptor (ER) and progesterone receptor (PR) are important prognostic factors indicating higher recovery rate in the breast cancer patients. Currently, immunohistochemical (IHC) staining is a conventional method to identify expression of ER and PR. If a breast cancer patient expresses ER or PR, a chemotherapy with estrogen inhibitors such as tamoxifen is supposed to be effective. Although IHC staining is a reliable method, it may not a useful method for continuous monitoring of ER and PR expression changes in multiple breast cancer patients. In the present study, we evaluated an alternative method of IHC for detection of ER and PR expression. A quantitative RT-PCR method called 'the BrightGen HR RT-qDx assay' was employed to detect mRNA expression of the nuclear receptors in 199 formalin-fixed paraffin-embedded (FFPE) breast cancer tissue samples. Among the ER/PR positive samples by IHC, 83 were determined positive and 16 were determined negative for the nuclear receptor mRNA by the quantitative RT-PCR method. Among the ER/PR negative samples by IHC, 37 were determined negative and 2 were determined positive by the quantitative RT-PCR method. The overall sensitivity and specificity of the quantitative RT-PCR method were 83.8% and 94.8% (P = 0.0026), respectively. We also optimized the quantitative RT-PCR method by setting up the diagnostic cut-off value using the likelihood ratio. The highest likelihood ratio was when the expression levels of the relative nuclear receptor mRNA passed 103.3 at which sensitivity and specificity was highest. These data suggest that BrightGen HR RT-qDx assay could be an alternative method for detection of the prognostic factors of nuclear receptors expressed in breast cancer patients for providing essential information for therapeutic application of tamoxifen.
authors.affiliation: M&D, Inc., Wonju Eco Environmental Technology Center Gangwon, Republic of Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Gangwon, Republic of Korea ; Department of Clinical Laboratory Science, College of Medical Science, Daegu Haany University Daegu, Republic of Korea.
authors.forename: Sangjung
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Gangwon, Republic of Korea ; Institute for Life Science and Biotechnology, Yonsei University Seoul, Republic of Korea.
authors.forename: Sunghyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Gangwon, Republic of Korea.
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Department of Clinical Laboratory Science, Hyejeon College Chungnam, Republic of Korea.
authors.forename: Dongsup
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Surgery, Yonsei University College of Medicine Seoul, Republic of Korea.
authors.forename: Seungil
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, College of Natural Sciences, Hoseo University Chungnam, Republic of Korea.
authors.forename: Dongju
authors.initials: D
authors.lastname: Jung
authors.affiliation: Department of Pathology, Wonju College of Medicine, Yonsei University Gangwon, Republic of Korea.
authors.forename: Kwang Hwa
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University Wonju, Gangwon, Republic of Korea.
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Lee
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D006801:Humans; D007150:Immunohistochemistry; D016013:Likelihood Functions; D061986:MCF-7 Cells; D016612:Paraffin Embedding; D018579:Patient Selection; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000235:genetics*; D011980:Receptors, Progesterone / Q000235:genetics*; D013629:Tamoxifen / Q000627:therapeutic use*; D016707:Tissue Fixation / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D004965:Estrogen Antagonists; D005404:Fixatives; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D005557:Formaldehyde
keywords: Breast cancer; ER; FFPE; PR; RT-qPCR; molecular diagnosis