Prognostic significance of UBE2C mRNA expression in high-risk early breast cancer. A Hellenic Cooperative Oncology Group (HeCOG) Study

Psyrri, Amanda; Kalogeras, Konstantine T.; Kronenwett, Ralf; Wirtz, Ralph M.; Batistatou, Anna; Bournakis, Evangelos; Timotheadou, Eleni; Gogas, Helen; Aravantinos, G.; Christodoulou, Christos; Makatsoris, Thomas; Linardou, Helena; Pectasides, Dimitrios; Pavlidis, Nicholas; Economopoulos, Theofanis; Fountzilas, George

doi:10.1093/annonc/mdr527

Cited by 68 publications

(64 citation statements)

References 30 publications

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“…A significant trend was seen for increased AURKA (p = 0.0001) and SURVIVIN (p = 0.0051) expression in high-grade breast tumours (Fig. 3a, Cochran-Armitage Trend test), as previously reported [19,26,[33][34][35][36][37], independent of breast cancer subtype in a multivariate analysis (Supplementary Table 4). A significant association for high AURKA expression with positive node status was also identified, independent of breast cancer subtype, in keeping with a recent study [38] (Fig.…”

Section: Mitotic Regulator Expression and Prognosissupporting

confidence: 82%

Expression of regulators of mitotic fidelity are associated with intercellular heterogeneity and chromosomal instability in primary breast cancer

Roylance

Endesfelder

Jamal‐Hanjani

et al. 2014

Breast Cancer Res Treat

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Regulators of transition through mitosis such as SURVIVIN and Aurora kinase A (AURKA) have been previously implicated in the initiation of chromosomal instability (CIN), a driver of intratumour heterogeneity. We investigate the relationship between protein expression of these genes and directly quantified CIN, and their prognostic utility in breast cancer. The expression of SURVIVIN and AURKA was determined by immunohistochemistry in a cohort of 426 patients with primary breast cancer. The association between protein expression and histopathological characteristics, clinical outcome and CIN status, as determined by centromeric FISH and defined by modal centromere deviation, was analysed. Significantly poorer clinical outcome was observed in patients with high AURKA expression levels. Expression of SURVIVIN was elevated in ER-negative relative to ER-positive breast cancer. Both AURKA and SURVIVIN increased expression were significantly associated with breast cancer grade. There was a significant association between increased CIN and both increased AURKA and SURVIVIN expression. AURKA gene amplification was also associated with increased CIN. To our knowledge this is the largest study assessing CIN status in parallel with the expression of the mitotic regulators AURKA and SURVIVIN. These data suggest that elevated expression of AURKA and SURVIVIN, together with AURKA gene amplification, are associated with increased CIN in breast cancer, and may be used as a proxy for CIN in breast cancer samples in the absence of more advanced molecular measurements.

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Section: Mitotic Regulator Expression and Prognosissupporting

confidence: 82%

Expression of regulators of mitotic fidelity are associated with intercellular heterogeneity and chromosomal instability in primary breast cancer

Roylance

Endesfelder

Jamal‐Hanjani

et al. 2014

Breast Cancer Res Treat

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“…To assure optimal reactivity, immunostaining was applied 7 to 10 days after sectioning at the Laboratory of Molecular Oncology of the Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine. The staining procedures for HER2 (A0485 polyclonal antibody, dilution 1:200; Dako, Glostrup, Denmark), ER (clone 6F11, dilution 1:70; Novocastra, Leica Biosystems, Newcastle, UK), PgR (clone 1A6, dilution 1:70; Novocastra, Leica Biosystems), and Ki67 (clone MIB-1, dilution 1:70; Dako) were performed using a Bond Max autostainer (Leica Microsystems, Wetzlar, Germany), as previously described in detail [28], [29], [30], [31], [32].…”

Section: Methodsmentioning

confidence: 99%

“…More than one FFPE section (2-8 sections, 10 μm thick) was used for RNA extraction when the tumor surface of a given sample was less than 0.25 cm 2 . From each FFPE section or macrodissected tissue fragments, RNA was extracted using a standardized fully automated isolation method for total RNA from FFPE tissue based on germanium-coated magnetic beads (XTRAKT kit; STRATIFYER Molecular Pathology GmbH, Cologne, Germany) in combination with a liquid handling robot (XTRAKT XL; STRATIFYER Molecular Pathology GmbH), as previously described in detail [29], [31], [32], [40], [41]. The method involves extraction-integrated deparaffinization and DNase I digestion steps.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the Prognostic Value of RANK, OPG, and RANKL mRNA Expression in Early Breast Cancer Patients Treated with Anthracycline-Based Adjuvant Chemotherapy

Timotheadou

Kalogeras

Koliou

et al. 2017

Translational Oncology

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BACKGROUND: Prevention of bone metastases is a major issue for breast cancer patients, as it would improve quality of life in a population where long survival is anticipated. PATIENTS AND METHODS: Early breast cancer patients, who had been treated with anthracycline-based chemotherapy within two randomized trials, were included in the study. We evaluated, by quantitative reverse transcription–polymerase chain reaction, 819 formalin-fixed paraffin-embedded tumor tissue samples for mRNA expression of RANK, OPG, and RANKL, as well as their ratios, for potential prognostic significance for the development of bone metastases and also for disease-free survival (DFS) and overall survival. RESULTS: Median age was 52.7 years, whereas 54.2% of the patients were postmenopausal and 78.3% estrogen receptor/progesterone receptor positive. After a median follow-up of 119.9 months, 226 patients (27.6%) had died and 291 patients (35.5%) had disease progression. Low mRNA expression of RANKL was associated with postmenopausal status and greater number of positive lymph nodes (P = .002 and P < .001, respectively). In the univariate analysis, low RANKL mRNA expression was found to be an unfavorable factor for DFS [hazard ratio (HR) = 1.33, 95% confidence interval (CI) 1.05-1.68, Wald's P = .018] and bone metastasis–free survival (HR = 1.67, 95% CI 1.09-2.56, P = .018), although it did not retain its significance in the multivariate analysis. CONCLUSIONS: Low RANKL mRNA expression in early breast cancer patients is of prognostic significance for increased risk for relapse and bone metastases and might potentially guide clinical decision-making for the use of anti-RANKL agents in the treatment of early breast cancer patients at high risk for metastatic spread, provided that our findings are validated in independent cohorts.

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“…TMA sections or whole tissue sections (5 μm thick) were used for fluorescence in situ hybridization (FISH) analysis, using the ZytoLight ® SPEC HER2 / TOP2A /CEN17 triple color probe (ZytoVision, Bremerhaven, Germany), as previously described [27]. Four carcinoma cell lines (MDA-MB-231, MDA-MB-175, MDA-MB-453, and SK-BR-3) from the Oracle HER2 Control Slide (Leica Biosystems), with a known HER2 gene status, were also used as a control of the FISH assays and analyzed for HER2 genomic status.…”

Section: Methodsmentioning

confidence: 99%

The prognostic and predictive value of mRNA expression of vascular endothelial growth factor family members in breast cancer: a study in primary tumors of high-risk early breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial

et al. 2012

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IntroductionThe main prognostic variables in early breast cancer are tumor size, histological grade, estrogen receptor/progesterone receptor (ER/PgR) status, number of positive nodes and human epidermal growth factor receptor 2 (HER2) status. The present study evaluated the prognostic and/or predictive value of vascular endothelial growth factor (VEGF) family members in high-risk early breast cancer patients treated with adjuvant chemo-hormonotherapy.MethodsRNA was isolated from 308 formalin-fixed paraffin-embedded primary tumor samples from breast cancer patients enrolled in the HE10/97 trial, evaluating adjuvant dose-dense sequential chemotherapy with epirubicin followed by cyclophosphamide, methotrexate, fluorouracil (CMF) with or without paclitaxel (E-T-CMF versus E-CMF). A fully automated method based on magnetic beads was applied for RNA extraction, followed by one-step quantitative RT-PCR for mRNA analysis of VEGF-A, -B, -C and vascular endothelial growth factor receptor (VEGFR) 1, 2, 3.ResultsWith a median follow-up of 8 years, 109 patients (35%) developed a relapse and 80 patients (26%) died. In high VEGF-C and VEGFR1 mRNA expressing tumors, ER/PgR-negative tumors (Fisher's exact test, P = 0.001 and P = 0.021, respectively) and HER2-positive tumors (P <0.001 and P = 0.028, respectively) were more frequent than in low VEGF-C and VEGFR1 expressing tumors, respectively. From the VEGF family members evaluated, high VEGFR1 mRNA expression (above the 75th percentile) emerged as a significant negative prognostic factor for overall survival (OS; hazard ratio (HR) = 1.60, 95% confidence interval (CI): 1.01 to 2.55, Wald's P = 0.047) and disease-free survival (DFS; HR = 1.67, 95% CI: 1.13 to 2.48, P = 0.010), when adjusting for treatment group. High VEGF-C mRNA expression was predictive for benefit from adjuvant treatment with paclitaxel (E-T-CMF arm) for OS (test for interaction, Wald's P = 0.038), while in multivariate analysis the interaction of VEGF-C with taxane treatment was significant for both OS (Wald's P = 0.019) and DFS (P = 0.041) and continuous VEGF-B mRNA expression values for OS (P = 0.019).ConclusionsThe present study reports, for the first time, that VEGF-C mRNA overexpression, as assessed by qRT-PCR, has a strong predictive value in high-risk early breast cancer patients undergoing adjuvant paclitaxel-containing treatment. Further studies are warranted to validate the prognostic and/or predictive value of VEGF-B, VEGF-C and VEGFR1 in patients treated with adjuvant therapies and to reveal which members of the VEGF family could possibly be useful markers in identifying patients who will benefit most from anti-VEGF strategies.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12611000506998

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Prognostic significance of UBE2C mRNA expression in high-risk early breast cancer. A Hellenic Cooperative Oncology Group (HeCOG) Study

Abstract: High UBE2C mRNA expression was found to be of adverse prognostic significance in high-risk breast cancer patients. These findings need to be validated in larger cohorts.

Cited by 68 publications

References 30 publications

Expression of regulators of mitotic fidelity are associated with intercellular heterogeneity and chromosomal instability in primary breast cancer

Expression of regulators of mitotic fidelity are associated with intercellular heterogeneity and chromosomal instability in primary breast cancer

Evaluation of the Prognostic Value of RANK, OPG, and RANKL mRNA Expression in Early Breast Cancer Patients Treated with Anthracycline-Based Adjuvant Chemotherapy

The prognostic and predictive value of mRNA expression of vascular endothelial growth factor family members in breast cancer: a study in primary tumors of high-risk early breast cancer patients participating in a randomized Hellenic Cooperative Oncology Group trial

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