Associação Portuguesa de Investigação em Cancro
p-mTOR expression is associated with prognosis in luminal breast carcinoma
p-mTOR expression is associated with prognosis in luminal breast carcinoma
Francisco Beça1,2,3, Rosário André4,5, Duarte Saraiva Martins6, Tiago Bilhim7, Diana Martins2, Fernando Schmitt2,8,9
1 - Department of Medical Oncology, Dana-Farber Cancer Institute/Harvard Medical School, Boston, Massachusetts, USA
2 - IPATIMUP—Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
3 - Faculty of Medicine, Department of Pathology and Oncology, University of Porto, Porto, Portugal
4 - Champalimaud Clinical Centre, Champalimaud Foundation, Lisbon, Portugal
5 - Department of Genetics, Oncology and Human Toxicology, Faculdade de Ciencias Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
6 - Department of Pediatric Cardiology, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal
7 - Department of Radiology, Faculdade de Ciências Médicas, Universidade Nova de Lisboa and Hospital de São José, Centro Hospitalar de Lisboa Central, Lisbon, Portugal
8 - Faculty of Medicine, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
9 - Department of Pathology, University Health Network, Toronto, Canada
Abstract:
Aims: Despite considerable interest in the PI3K/AKT/mTOR pathway in breast carcinomas (BC), published data reports contradictory results regarding the association of phosphorylated mammalian target of Rapamycin (p-mTOR) expression with clinico-pathological features and prognosis in BC. Here, we evaluate the main clinico-pathological associations with p-mTOR expression in BC, with focus on the different molecular subtypes.
Methods: In this retrospective study, 331 BC patients were included in final analysis. Outcome measures included disease-free survival (DFS) and overall survival (OS) times. Baseline data and outcome measures were compared between immunohistochemical p-mTOR expressing and non-expressing BCs. Subgroup analysis was performed to assess the effect of p-mTOR expression in the outcome for each BC molecular subtype.
Results: 43.8% of the tumours were positive for p-mTOR, with a significant correlation between p-mTOR expression with smaller (<2 cm) (p=0.021) and lower-grade tumours (p<0.001). Expression of p-mTOR was also associated with longer DFS (HR of 0.32, p<0.001) and OS (HR of 0.20, p<0.001). In a multivariable analysis, the HR remained significant with minimal change (HR=0.26, p=0.002 for OS; HR=0.40, p=0.002 for DFS). In subgroup analysis, luminal p-mTOR-expressing tumours demonstrated longer DFS and OS (HR 0.33, p=0.003; HR 0.20, p=0.003, respectively) independently of size, grade, lymph node status and Her-2 overexpression.
Conclusions: p-mTOR expression is associated with smaller, lower-grade and with luminal BC. In multivariable analysis, p-mTOR expression was associated with longer DFS and OS, independently of the size, grade and lymph node status, especially in luminal BCs.
Journal of Clinical Pathology
