Georgios Lazaridis1, Vassiliki Kotoula2,3, Eleni Vrettou2, Ioannis Kostopoulos2, Kyriaki Manousou4, Kyriaki Papadopoulou3, Eleni Giannoulatou5,6, Mattheos Bobos3, Maria Sotiropoulou7, George Pentheroudakis8, Ioannis Efstratiou2, Alexandra Papoudou-Bai9, Amanda Psyrri10, Christos Christodoulou11, Helen Gogas12, Angelos Koutras13, Eleni Timotheadou14, Dimitrios Pectasides15, Flora Zagouri16, George Fountzilas3,17. 1. Department of Medical Oncology, Faculty of Medicine Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Thessaloniki, Greece georlaz@yahoo.gr. 2. Department of Pathology, School of Health Sciences, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. 3. Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, Thessaloniki, Greece. 4. Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece. 5. Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia. 6. The University of New South Wales, Kensington, NSW, Australia. 7. Department of Pathology, Alexandra Hospital, Athens, Greece. 8. Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece. 9. Department of Pathology, Ioannina University Hospital, Ioannina, Greece. 10. Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece. 11. Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece. 12. First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 13. Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece. 14. Department of Medical Oncology, Faculty of Medicine Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Thessaloniki, Greece. 15. Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece. 16. Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece. 17. Aristotle University of Thessaloniki, Thessaloniki, Greece.
Abstract
BACKGROUND/AIM: PTEN-loss and PIK3CA mutations have been addressed as markers of PI3K activation in breast cancer. We evaluated these markers in early high-risk breast cancer (EBC) focusing on PTEN immunohistochemistry (IHC) issues, particularly in HER2-positive disease. MATERIALS AND METHODS: We examined PTEN-loss and PIK3CA mutations in 1265 EBC patients treated with adjuvant chemotherapy within two clinical trials. Two different methods for the evaluation of PTEN IHC were used, one upfront binary (loss; no-loss) and the other initially multi-scale allowing for the classification of "grey zone" tumors with low and very low PTEN protein expression. RESULTS: PTEN-loss (33.4% and 22.1%, depending on the IHC method) and PIK3CA mutations (29.6%) were associated with ER/PgR/HER2-negative and ER/PgR-positive disease, respectively. Concordance of the two IHC methods was moderate (Cohen's kappa 0.624). PTEN-loss discrepancy and intra-tumor heterogeneity concerned "grey zone" tumors that were prevalent among HER2-positive cancers. PTEN-loss independently conferred higher risk for relapse and death. Compared to single PIK3CA mutations,single PTEN-loss was independently associated with increased risk for relapse and death. Depending on the evaluation method, in HER2-positive cancer, PTEN-loss was without- or of marginal unfavorable prognostic significance. CONCLUSION: In EBC, PTEN-loss is an independent predictor of poor outcome. When occurring singly, PTEN-loss and PIK3CA mutations have opposite prognostic impact. In HER2-positive disease, assessment of PTEN-loss by IHC appears unreliable and the marker is without clear prognostic significance. Copyright
BACKGROUND/AIM: PTEN-loss and PIK3CA mutations have been addressed as markers of PI3K activation in breast cancer. We evaluated these markers in early high-risk breast cancer (EBC) focusing on PTEN immunohistochemistry (IHC) issues, particularly in HER2-positive disease. MATERIALS AND METHODS: We examined PTEN-loss and PIK3CA mutations in 1265 EBC patients treated with adjuvant chemotherapy within two clinical trials. Two different methods for the evaluation of PTEN IHC were used, one upfront binary (loss; no-loss) and the other initially multi-scale allowing for the classification of "grey zone" tumors with low and very low PTEN protein expression. RESULTS:PTEN-loss (33.4% and 22.1%, depending on the IHC method) and PIK3CA mutations (29.6%) were associated with ER/PgR/HER2-negative and ER/PgR-positive disease, respectively. Concordance of the two IHC methods was moderate (Cohen's kappa 0.624). PTEN-loss discrepancy and intra-tumor heterogeneity concerned "grey zone" tumors that were prevalent among HER2-positive cancers. PTEN-loss independently conferred higher risk for relapse and death. Compared to single PIK3CA mutations,single PTEN-loss was independently associated with increased risk for relapse and death. Depending on the evaluation method, in HER2-positive cancer, PTEN-loss was without- or of marginal unfavorable prognostic significance. CONCLUSION: In EBC, PTEN-loss is an independent predictor of poor outcome. When occurring singly, PTEN-loss and PIK3CA mutations have opposite prognostic impact. In HER2-positive disease, assessment of PTEN-loss by IHC appears unreliable and the marker is without clear prognostic significance. Copyright
Authors: Rulla M Tamimi; A Heather Eliassen; Tengteng Wang; Yujing J Heng; Gabrielle M Baker; Vanessa C Bret-Mounet; Liza M Quintana; Lisa Frueh; Susan E Hankinson; Michelle D Holmes; Wendy Y Chen; Walter C Willett; Bernard Rosner Journal: Cancer Epidemiol Biomarkers Prev Date: 2022-10-04 Impact factor: 4.090
Authors: Terrick Andey; Michael M Attah; Nana Adwoa Akwaaba-Reynolds; Sana Cheema; Sara Parvin-Nejad; George K Acquaah-Mensah Journal: Gene X Date: 2020-05-01