Expression of neurotensin receptor-1 (NTS) in primary breast tumors, cellular distribution, and association with clinical and biological factors.

PURPOSE

Neurotensin receptor-1 (NTS) is increasingly recognized as a potential target in diverse tumors including breast cancer, but factors associated with NTS expression have not been fully clarified.

METHODS

We studied NTS expression using the Tissue MicroArray (TMA) of primary breast tumors from Institut Bergonié. We also studied association between NTS expression and clinical, pathological, and biological parameters, as well as patient outcomes.

RESULTS

Out of 1419 primary breast tumors, moderate to strong positivity for NTS (≥ 10% of tumoral cells stained) was seen in 459 samples (32.4%). NTS staining was cytoplasmic in 304 tumors and nuclear in 155 tumors, a distribution which appeared mutually exclusive. Cytoplasmic overexpression of NTS was present in 21.5% of all breast tumors. In multivariate analysis, factors associated with cytoplasmic overexpression of NTS in breast cancer samples were higher tumor grade, Ki67 ≥ 20%, and higher pT stage. Cytoplasmic NTS 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 NTS were estrogen receptor (ER) positivity, low E&E (Elston and Ellis) grade, Ki67 < 20%, and lower pT stage. In NTS-positive samples, cytoplasmic expression of NTS was associated with shorter 10-year metastasis-free interval (p = 0.033) compared to NTS nuclear staining. Ancillary analysis showed NTS expression in 73% of invaded lymph nodes from NTS-positive primaries.

CONCLUSION

NTS 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 NTS-targeting strategy, including radiopharmaceuticals for imaging and therapy.