Details

Autor(en) / Beteiligte

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

Titel

Trop-2 is a determinant of breast cancer survival

Ist Teil von

• PloS one, 2014-05, Vol.9 (5), p.e96993-e96993

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.