Prediction of Oncotype DX and TAILORx risk categories using histopathological and immunohistochemical markers by classification and regression tree (CART) analysis |
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| Authors: | Helen Ingoldsby Mark Webber Deirdre Wall Carl Scarrott John Newell Grace Callagy |
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| Affiliation: | 1. Discipline of Pathology, National University of Ireland, Galway, Ireland;2. Department of Pathology, Galway University Hospitals, Ireland;3. School of Mathematics, Statistics and Applied Maths and HRB Clinical Research Facility, National University of Ireland, Galway, Ireland;4. Department of Mathematics and Statistics, University of Canterbury, Christchurch, New Zealand;1. Clinique de Genolier, Switzerland;2. Leiden University Medical Center, The Netherlands;3. Medical School, University of Athens, Athens, Greece;4. Ontario Institute for Cancer Research, Toronto, Canada;5. Weston Park Hospital NHS Trust, Sheffield, United Kingdom;1. Nuclear Medicine Department, Germans Trias i Pujol University Hospital, Carretera del Canyet, Badalona, Spain;2. Oncology Department, Catalan Institute of Oncology, Germans Trias i Pujol University Hospital, Carretera del Canyet, Badalona, Spain;3. Pathology Department, Germans Trias i Pujol University Hospital, Carretera del Canyet, Badalona, Spain;4. Radiology Department, Germans Trias i Pujol University Hospital, Carretera del Canyet, Badalona, Spain;5. Surgery Department, Germans Trias i Pujol University Hospital, Carretera del Canyet, Badalona, Spain;6. Gynecology Department, Germans Trias i Pujol University Hospital, Carretera del Canyet, Badalona, Spain;1. Department of Surgery, Jeroen Bosch Ziekenhuis, P.O. Box 90153, 5200 ME ''s-Hertogenbosch, The Netherlands;2. Department of Radiology, Jeroen Bosch Ziekenhuis, ''s-Hertogenbosch, The Netherlands;3. Department of Pathology, Jeroen Bosch Ziekenhuis, ''s-Hertogenbosch, The Netherlands;4. Department of Oncology, Jeroen Bosch Ziekenhuis, ''s-Hertogenbosch, The Netherlands;1. Division of Gynecological Oncology, Fondazione del Piemonte per l''Oncologia, Turin, Italy;2. Institute for Cancer Research and Treatment (IRCC) of Candiolo, Strada Provinciale 142, Km. 3.95, 10060 Candiolo, Turin, Italy;3. The Clinical Trials Group, Dept. of Surgery, University College of London (UCL), Clerkenwell Bldg, Whittington Campus, London N19 5LW, UK |
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| Abstract: | Oncotype DX is an RT-PCR assay used to predict which patients with ER-positive node-negative (NN) disease will benefit from chemotherapy. Each patient is stratified into a risk category based on a recurrence score (RS) and the TAILORx trial is determining the benefit of chemotherapy for patients with mid-range RSs.We tested if Oncotype DX and TAILORx risk categories could be predicted by standard pathological features and protein markers corresponding to 10 genes in the assay (ER, PR, Ki67, HER2, BCL2, CD68, Aurora A kinase, survivin, cyclin B1 and BAG1) on 52 patients who enrolled on TAILORx. Immunohistochemistry for the protein markers was performed on whole tissue sections.Classification and regression tree (CART) analysis correctly classified 69% of cases into Oncotype DX risk categories based on the expression of PR, survivin and nuclear pleomorphism. All tumours with PR staining (Allred score ≥2) and marked nuclear pleomorphism were in the high-risk category. No case with PR <2, low survivin (≤15.5%) and nuclear pleomorphism <3 was high-risk. Similarly, 77% of cases were correctly classified into TAILORx categories based on nuclear pleomorphism, survivin, BAG1 and cyclin B1. Ki67 was the only variable that predicted the absolute RS with a cut-off for positivity of 15% (p = 0.003).In conclusion, CART revealed key predictors including proliferation markers, PR and nuclear pleomorphism that correctly classified over two thirds of ER-positive NN cancers into Oncotype DX and TAILORx risk categories. These variables could be used as an alternative to the RT-PCR assay to reduce the number of patients requiring Oncotype DX testing. |
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| Keywords: | Oncotype DX TAILORx Breast cancer Immunohistochemistry PR Ki67 |
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