Τίτλος:
Adjusting breast cancer patient prognosis with non-HER2-gene patterns on chromosome 17
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: HER2 and TOP2A gene status are assessed for diagnostic and research purposes in breast cancer with fluorescence in situ hybridization (FISH). However, FISH probes do not target only the annotated gene, while chromosome 17 (chr17) is among the most unstable chromosomes in breast cancer. Here we asked whether the status of specifically targeted genes on chr17 might help in refining prognosis of early high-risk breast cancer patients. Methods: Copy numbers (CN) for 14 genes on chr17, 4 of which were within and 10 outside the core HER2 amplicon (HER2- and non-HER2-genes, respectively) were assessed with qPCR in 485 paraffin-embedded tumor tissue samples from breast cancer patients treated with adjuvant chemotherapy in the frame of two randomized phase III trials. Principal Findings: HER2-genes CN strongly correlated to each other (Spearman's rho >0.6) and were concordant with FISH HER2 status (Kappa 0.6697 for ERBB2 CN). TOP2A CN were not concordant with TOP2A FISH status (Kappa 0.1154). CN hierarchical clustering revealed distinct patterns of gains, losses and complex alterations in HER2- and non-HER2-genes associated with IHC4 breast cancer subtypes. Upon multivariate analysis, non-HER2-gene gains independently predicted for shorter disease-free survival (DFS) and overall survival (OS) in patients with triple-negative cancer, as compared to luminal and HER2-positive tumors (interaction p = 0.007 for DFS and p = 0.011 for OS). Similarly, non-HER2-gene gains were associated with worse prognosis in patients who had undergone breast-conserving surgery as compared to modified radical mastectomy (p = 0.004 for both DFS and OS). Non-HER2-gene losses were unfavorable prognosticators in patients with 1-3 metastatic nodes, as compared to those with 4 or more nodes (p = 0.017 for DFS and p = 0.001 for OS). Conclusions: TOP2A FISH and qPCR may not identify the same pathology on chr17q. Non-HER2 chr17 CN patterns may further predict outcome in breast cancer patients with known favorable and unfavorable prognosis. © 2014 Kotoula et al.
Συγγραφείς:
Kotoula, V.
Bobos, M.
Alexopoulou, Z.
Papadimitriou, C.
Papadopoulou, K.
Charalambous, E.
Tsolaki, E.
Xepapadakis, G.
Nicolaou, I.
Papaspirou, I.
Aravantinos, G.
Christodoulou, C.
Efstratiou, I.
Gogas, H.
Fountzilas, G.
Εκδότης:
Public Library of Science
Λέξεις-κλειδιά:
anthracycline; trastuzumab; DNA binding protein; DNA topoisomerase (ATP hydrolysing); DNA topoisomerase II alpha; epidermal growth factor receptor 2; ERBB2 protein, human; tumor antigen, adult; amplicon; article; breast cancer; cancer adjuvant therapy; cancer prognosis; CDC6 gene; chromosome 17; controlled study; disease free survival; ERBB2 gene; female; fluorescence in situ hybridization; gene cluster; gene dosage; gene interaction; gene loss; gene targeting; HER2 gene; high risk patient; human; human tissue; IGFBP gene; KRT20 gene; MAP2K4 gene; NOS2 gene; oncogene; overall survival; partial mastectomy; phase 3 clinical trial (topic); polymerase chain reaction; PSMD3 gene; randomized controlled trial (topic); RARA gene; SMARCE1 gene; STARD3 gene; STAT3 gene; THRA gene; TOP2A gene; TP53 gene; triple negative breast cancer; Breast Neoplasms; chromosomal instability; chromosome 17; clinical trial; genetics; metabolism; middle aged; multicenter study; pathology; phase 3 clinical trial; randomized controlled trial; survival rate, Adult; Antigens, Neoplasm; Breast Neoplasms; Chromosomal Instability; Chromosomes, Human, Pair 17; Disease-Free Survival; DNA Topoisomerases, Type II; DNA-Binding Proteins; Female; Humans; In Situ Hybridization, Fluorescence; Middle Aged; Receptor, ErbB-2; Survival Rate
DOI:
10.1371/journal.pone.0103707
