Clément Morgat1,2, Véronique Brouste3, Adrien Chastel4,5, Valérie Vélasco6,7, Gaétan Macgrogan6,7, Elif Hindié4,5,8. 1. Nuclear Medicine Department, University Hospital of Bordeaux, 33076, Bordeaux, France. clement.morgat@u-bordeaux.fr. 2. University of Bordeaux, CNRS, EPHE, INCIA, UMR 5287, 33000, Bordeaux, France. clement.morgat@u-bordeaux.fr. 3. Clinical and Epidemiological Research Unit, Institut Bergonié, 33076, Bordeaux, France. 4. Nuclear Medicine Department, University Hospital of Bordeaux, 33076, Bordeaux, France. 5. University of Bordeaux, CNRS, EPHE, INCIA, UMR 5287, 33000, Bordeaux, France. 6. Surgical Pathology Unit, Department of Biopathology, Institut Bergonié, 33076, Bordeaux, France. 7. INSERM, ACTION U1218, 33076, Bordeaux, France. 8. Institut Universitaire de France (IUF), Paris, France.
Abstract
PURPOSE: Neurotensin receptor-1 (NTS1) is increasingly recognized as a potential target in diverse tumors including breast cancer, but factors associated with NTS1 expression have not been fully clarified. METHODS: We studied NTS1 expression using the Tissue MicroArray (TMA) of primary breast tumors from Institut Bergonié. We also studied association between NTS1 expression and clinical, pathological, and biological parameters, as well as patient outcomes. RESULTS: Out of 1419 primary breast tumors, moderate to strong positivity for NTS1 (≥ 10% of tumoral cells stained) was seen in 459 samples (32.4%). NTS1 staining was cytoplasmic in 304 tumors and nuclear in 155 tumors, a distribution which appeared mutually exclusive. Cytoplasmic overexpression of NTS1 was present in 21.5% of all breast tumors. In multivariate analysis, factors associated with cytoplasmic overexpression of NTS1 in breast cancer samples were higher tumor grade, Ki67 ≥ 20%, and higher pT stage. Cytoplasmic NTS1 was more frequent in tumors other than luminal A (30% versus 17.3%; p < 0.0001). Contrastingly, the main "correlates" of a nuclear location of NTS1 were estrogen receptor (ER) positivity, low E&E (Elston and Ellis) grade, Ki67 < 20%, and lower pT stage. In NTS1-positive samples, cytoplasmic expression of NTS1 was associated with shorter 10-year metastasis-free interval (p = 0.033) compared to NTS1 nuclear staining. Ancillary analysis showed NTS1 expression in 73% of invaded lymph nodes from NTS1-positive primaries. CONCLUSION: NTS1 overexpression was found in about one-third of breast tumors from patients undergoing primary surgery with two distinct patterns of distribution, cytoplasmic distribution being more frequent in aggressive subtypes. These findings encourage the development of NTS1-targeting strategy, including radiopharmaceuticals for imaging and therapy.
PURPOSE: Neurotensin receptor-1 (NTS1) is increasingly recognized as a potential target in diverse tumors including breast cancer, but factors associated with NTS1 expression have not been fully clarified. METHODS: We studied NTS1 expression using the Tissue MicroArray (TMA) of primary breast tumors from Institut Bergonié. We also studied association between NTS1 expression and clinical, pathological, and biological parameters, as well as patient outcomes. RESULTS: Out of 1419 primary breast tumors, moderate to strong positivity for NTS1 (≥ 10% of tumoral cells stained) was seen in 459 samples (32.4%). NTS1 staining was cytoplasmic in 304 tumors and nuclear in 155 tumors, a distribution which appeared mutually exclusive. Cytoplasmic overexpression of NTS1 was present in 21.5% of all breast tumors. In multivariate analysis, factors associated with cytoplasmic overexpression of NTS1 in breast cancer samples were higher tumor grade, Ki67 ≥ 20%, and higher pT stage. Cytoplasmic NTS1 was more frequent in tumors other than luminal A (30% versus 17.3%; p < 0.0001). Contrastingly, the main "correlates" of a nuclear location of NTS1 were estrogen receptor (ER) positivity, low E&E (Elston and Ellis) grade, Ki67 < 20%, and lower pT stage. In NTS1-positive samples, cytoplasmic expression of NTS1 was associated with shorter 10-year metastasis-free interval (p = 0.033) compared to NTS1 nuclear staining. Ancillary analysis showed NTS1 expression in 73% of invaded lymph nodes from NTS1-positive primaries. CONCLUSION: NTS1 overexpression was found in about one-third of breast tumors from patients undergoing primary surgery with two distinct patterns of distribution, cytoplasmic distribution being more frequent in aggressive subtypes. These findings encourage the development of NTS1-targeting strategy, including radiopharmaceuticals for imaging and therapy.
Authors: Willi Sauerbrei; Sheila E Taube; Lisa M McShane; Margaret M Cavenagh; Douglas G Altman Journal: J Natl Cancer Inst Date: 2018-08-01 Impact factor: 13.506
Authors: Kimberly J Riehle; Heidi L Kenerson; Kevin M Riggle; Rigney Turnham; Kevin Sullivan; Renay Bauer; John D Scott; Raymond S Yeung Journal: Oncotarget Date: 2019-08-20