Τίτλος:
Protein expression patterns of cell cycle regulators in operable breast cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background-Aim: To evaluate the prognostic role of elaborate molecular clusters encompassing cyclin D1, cyclin E1, p21, p27 and p53 in the context of various breast cancer subtypes. Methods: Cyclin E1, cyclin D1, p53, p21 and p27 were evaluated with immunohistochemistry in 1077 formalin-fixed paraffin-embedded tissues from breast cancer patients who had been treated within clinical trials. Jaccard distances were computed for the markers and the resulted matrix was used for conducting unsupervised hierarchical clustering, in order to identify distinct groups correlating with prognosis. Results: Luminal B and triple-negative (TNBC) tumors presented with the highest and lowest levels of cyclin D1 expression, respectively. By contrast, TNBC frequently expressed Cyclin E1, whereas ER-positive tumors did not. Absence of Cyclin D1 predicted for worse OS, while absence of Cyclin E1 for poorer DFS. The expression patterns of all examined proteins yielded 3 distinct clusters; (1) Cyclin D1 and/or E1 positive with moderate p21 expression; (2) Cyclin D1 and/or E1, and p27 positive, p53 protein negative; and, (3) Cyclin D1 or E1 positive, p53 positive, p21 and p27 negative or moderately positive. The 5-year DFS rates for clusters 1, 2 and 3 were 70.0%, 79.1%, 67.4% and OS 88.4%, 90.4%, 78.9%, respectively. Conclusions: It seems that the expression of cell cycle regulators in the absence of p53 protein is associated with favorable prognosis in operable breast cancer. © 2017 Zagouri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Συγγραφείς:
Zagouri, F.
Kotoula, V.
Kouvatseas, G.
Sotiropoulou, M.
Koletsa, T.
Gavressea, T.
Valavanis, C.
Trihia, H.
Bobos, M.
Lazaridis, G.
Koutras, A.
Pentheroudakis, G.
Skarlos, P.
Bafaloukos, D.
Arnogiannaki, N.
Chrisafi, S.
Christodoulou, C.
Papakostas, P.
Aravantinos, G.
Kosmidis, P.
Karanikiotis, C.
Zografos, G.
Papadimitriou, C.
Fountzilas, G.
Εκδότης:
Public Library of Science
Λέξεις-κλειδιά:
cyclin D1; cyclin E1; formaldehyde; oncoprotein; paraffin; protein p21; protein p27; protein p53; unclassified drug; antineoplastic agent; CCND1 protein, human; CCNE1 protein, human; CDKN1A protein, human; cyclin D1; cyclin dependent kinase inhibitor 1A; cyclin dependent kinase inhibitor 1B; cyclin E; oncoprotein; protein p53, adult; aged; Article; breast cancer; cancer prognosis; cancer tissue; cell cycle regulation; cluster analysis; controlled study; disease free survival; female; human; human tissue; immunohistochemistry; major clinical study; multivariate analysis; overall survival; protein expression; triple negative breast cancer; breast; Breast Neoplasms; clinical trial; drug effects; middle aged; pathology; phase 3 clinical trial; prognosis; randomized controlled trial; survival analysis; Triple Negative Breast Neoplasms; young adult, Adult; Aged; Antineoplastic Agents; Breast; Breast Neoplasms; Cyclin D1; Cyclin E; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Female; Humans; Immunohistochemistry; Middle Aged; Oncogene Proteins; Prognosis; Survival Analysis; Triple Negative Breast Neoplasms; Tumor Suppressor Protein p53; Young Adult
DOI:
10.1371/journal.pone.0180489
