Open AccessCyclin E correlates with manganese superoxide dismutase expression and predicts survival in early breast cancer patients receiving adjuvant epirubicin‐based chemotherapy
Author(s) -
Sgambato Alessandro,
Camerini Andrea,
Collecchi Paola,
Graziani Cristina,
Bevilacqua Generoso,
Capodanno Alessandra,
Migaldi Mario,
Masciullo Valeria,
Scambia Giovanni,
Rossi Giulio,
Cittadini Achille,
Amoroso Domenico
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01141.x
Subject(s) - epirubicin , anthracycline , breast cancer , medicine , doxorubicin , chemotherapy , oncology , cancer , cyclin e , cyclin d1 , survival analysis , immunohistochemistry , adjuvant therapy , cancer research , cell cycle
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. ( Cancer Sci 2009; 100: 1026–1033)