Trop-2 is a determinant of breast cancer survival.
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.
Unit of Medical Statistics, Biometry and Bioinformatics "Giulio A. Maccacaro", Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy.
Federico
F
Ambrogi
Unit of Medical Statistics, Biometry and Bioinformatics "Giulio A. Maccacaro", Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy.
Marco
M
Fornili
Unit of Medical Statistics, Biometry and Bioinformatics "Giulio A. Maccacaro", Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy.
Patrizia
P
Boracchi
Unit of Cancer Pathology, Department of Biomedical Sciences and CeSI, Fondazione 'G. D'Annunzio', University of Chieti, Chieti, Italy.
Marco
M
Trerotola
Unit of Cancer Pathology, Department of Biomedical Sciences and CeSI, Fondazione 'G. D'Annunzio', University of Chieti, Chieti, Italy.
Valeria
V
Relli
Unit of Cancer Pathology, Department of Biomedical Sciences and CeSI, Fondazione 'G. D'Annunzio', University of Chieti, Chieti, Italy.
Pasquale
P
Simeone
Unit of Cancer Pathology, Department of Biomedical Sciences and CeSI, Fondazione 'G. D'Annunzio', University of Chieti, Chieti, Italy; MediaPharma s.r.l., CeSI, University 'G. D'Annunzio', Chieti, Italy.
Rossana
R
La Sorda
Unit of Cancer Pathology, Department of Biomedical Sciences and CeSI, Fondazione 'G. D'Annunzio', University of Chieti, Chieti, Italy; MediaPharma s.r.l., CeSI, University 'G. D'Annunzio', Chieti, Italy.
Rossano
R
Lattanzio
Section of Surgical Pathology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy.
Patrizia
P
Querzoli
Section of Surgical Pathology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy.
Massimo
M
Pedriali
Unit of Cancer Pathology, Department of Biomedical Sciences and CeSI, Fondazione 'G. D'Annunzio', University of Chieti, Chieti, Italy; MediaPharma s.r.l., CeSI, University 'G. D'Annunzio', Chieti, Italy.
Mauro
M
Piantelli
Unit of Medical Statistics, Biometry and Bioinformatics "Giulio A. Maccacaro", Department of Clinical Sciences and Community Health, University of Milan, Milano, Italy; Fondazione IRCCS, Istituto Nazionale Tumori, Milano, Italy.
Elia
E
Biganzoli
Unit of Cancer Pathology, Department of Biomedical Sciences and CeSI, Fondazione 'G. D'Annunzio', University of Chieti, Chieti, Italy; Department of Neurosciences, Imaging and Clinical Sciences - Physiology and Physiopathology, University of Chieti, Chieti, Italy; Oncoxx Biotech s.r.l., Chieti, Italy.
Saverio
S
Alberti
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499380:TACSTD2 protein, human