title: Cyclin E correlates with manganese superoxide dismutase expression and predicts survival in early breast cancer patients receiving adjuvant epirubicin-based chemotherapy.
abstract: Anthracycline-based chemotherapy represents a milestone in the treatment of breast cancer. We previously demonstrated in an in vitro model that cyclin E overexpression is associated with increased expression of manganese superoxide dismutase (MnSOD) and resistance to doxorubicin. In the present study, immunohistochemical expression of cyclin E and MnSOD was evaluated in 134 early breast cancer patients receiving adjuvant epirubicin-based chemotherapy regimens containing epirubicin. Both parameters were correlated with the available clinicopathological parameters and with the outcome of patients. Overexpression of cyclin E and MnSOD was detected in 46 (34.3%) and 56 (41.8%) patients, respectively, and expression levels of the two proteins were related. Disease-free and alive patients displayed a lower mean percentage of cyclin E-expressing cells than relapsed and dead patients, respectively. Kaplan-Meier survival analysis demonstrated a significant separation between high versus low cyclin E-expressing tumors in terms of overall survival (P = 0.038 by log-rank). Similar results were obtained considering the subset of node-negative patients separately. No significant relationship with patient outcome was observed for MnSOD expression levels. At multivariate analysis cyclin E failed to demonstrate an independent prognostic value. In conclusion, the results of the present study support previous evidence that increased cyclin E expression is associated with higher MnSOD expression levels and poorer outcome, at least as evaluated in terms of overall survival. Further studies are warranted to evaluate the usefulness of cyclin E as a prognostic marker to identify breast cancer patients at higher risk of death from the disease when treated with adjuvant anthracycline-based therapy.
authors.affiliation: Giovanni XXIII Cancer Research Center, Catholic University of Sacred Heart, Rome, Italy. asgambato@rm.unicatt.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sgambato
authors.forename: Andrea
authors.initials: A
authors.lastname: Camerini
authors.forename: Paola
authors.initials: P
authors.lastname: Collecchi
authors.forename: Cristina
authors.initials: C
authors.lastname: Graziani
authors.forename: Generoso
authors.initials: G
authors.lastname: Bevilacqua
authors.forename: Alessandra
authors.initials: A
authors.lastname: Capodanno
authors.forename: Mario
authors.initials: M
authors.lastname: Migaldi
authors.forename: Valeria
authors.initials: V
authors.lastname: Masciullo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.forename: Achille
authors.initials: A
authors.lastname: Cittadini
authors.forename: Domenico
authors.initials: D
authors.lastname: Amoroso
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D019927:Cyclin E / Q000378:metabolism*; D018572:Disease-Free Survival; D015251:Epirubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013482:Superoxide Dismutase / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D000903:Antibiotics, Antineoplastic; D019927:Cyclin E; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015251:Epirubicin; D013482:Superoxide Dismutase