Trop-2 is a determinant of breast cancer survival

Federico Ambrogi, Marco Fornili, Patrizia Boracchi, Marco Trerotola, Valeria Relli, Pasquale Simeone, Rossana La Sorda, Rossano Lattanzio, Patrizia Querzoli, Massimo Pedriali, Mauro Piantelli, Elia Biganzoli, Saverio Alberti

Research output: Contribution to journalArticle

Abstract

Trop-2 is a calcium signal transducer that drives tumor growth. Anti-Trop-2 antibodies with selective reactivity versus Trop-2 maturation stages allowed to identify two different pools of Trop-2, one localized in the cell membrane and one in the cytoplasm. Of note, membrane-localized/functional Trop-2 was found to be differentially associated with determinants of tumor aggressiveness and distinct breast cancer subgroups. These findings candidated Trop-2 states to having an impact on cancer progression. We tested this model in breast cancer. A large, consecutive human breast cancer case series (702 cases; 8 years median follow-up) was analyzed by immunohistochemistry with anti-Trop-2 antibodies with selective reactivity for cytoplasmic-retained versus functional, membrane-associated Trop-2. We show that membrane localization of Trop-2 is an unfavorable prognostic factor for overall survival (1+ versus 0 for all deaths: hazard ratio, 1.63; P = 0.04), whereas intracellular Trop-2 has a favorable impact on prognosis, with an adjusted hazard ratio for all deaths of 0.48 (high versus low; P = 0.003). A corresponding impact of intracellular Trop-2 was found on disease relapse (high versus low: hazard ratio, 0.51; P = 0.004). Altogether, we demonstrate that the Trop-2 activation states are critical determinants of tumor progression and are powerful indicators of breast cancer patients survival.

Original languageEnglish
Article numbere96993
JournalPLoS One
Volume9
Issue number5
DOIs
Publication statusPublished - May 13 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Ambrogi, F., Fornili, M., Boracchi, P., Trerotola, M., Relli, V., Simeone, P., La Sorda, R., Lattanzio, R., Querzoli, P., Pedriali, M., Piantelli, M., Biganzoli, E., & Alberti, S. (2014). Trop-2 is a determinant of breast cancer survival. PLoS One, 9(5), [e96993]. https://doi.org/10.1371/journal.pone.0096993