Centromere 17 Copy Number Alteration: Negative Prognostic Factor in Invasive Breast Cancer?

2012 ◽  
Vol 136 (9) ◽  
pp. 993-1000 ◽  
Author(s):  
Stella Petroni ◽  
Teresa Addati ◽  
Eliseo Mattioli ◽  
Maria Angela Caponio ◽  
Carmela Quero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Copy Number ◽  
Growth Factor Receptor ◽  
Copy Number Gain ◽  
Chromosome 17 ◽  
Proliferation Index ◽  
Fish Analysis ◽  
Breast Cancers ◽  
Ki 67

Context.—Chromosome 17 polysomy has been identified in 5% to 50% of invasive breast cancers; even though a relationship with human epidermal growth factor receptor 2 (HER2/neu) status has been reported, other studies have shown that coincident centromere 17 (Cep17) amplification may be the cause of an overestimation of chromosome 17 polysomy in fluorescence in situ hybridization (FISH) testing. Objective.—To evaluate polysomy/amplification of Cep17 in invasive breast cancer with relation to proliferative activity (Ki-67), estrogen receptor, progesterone receptor, and HER2/neu status, in an attempt to identify a subgroup of patients with a worse prognosis. Design.—A total of 647 cases of invasive ductal breast cancer were collected and subjected to FISH analysis for HER2/neu gene and centromere 17 alteration, HercepTest for HER2/neu protein expression, and routine immunohistochemistry for Ki-67 and hormone receptor status. Results.—Copy number gain of Cep17 was observed in 27.3% of cases. Within this group, HER2/neu gene amplification was detected in 14.1% of cases, whereas HER2/neu expression was scored 3+ in 20.1% of cases; about half of the HER2/neu overexpressing cases (9.8%) did not show amplification by FISH. Moreover, 69% of polysomic cases showed high Ki-67 index. Conclusions.—(1) Centromere 17–altered cases are frequently HER2/neu overexpressing but not amplified, resulting in HercepTest/FISH disagreement; (2) HER2/neu amplification is seen at a higher incidence in cases without Cep17 copy number alterations, which are therefore not necessarily due to chromosome 17 disorder; (3) proliferation index is significantly higher in aneusomic tumors. These data suggest that the presence of Cep17 alterations could identify a subset of breast cancers with more aggressive biological and clinical behavior, which may show nonresponsiveness to conventional therapy independently of HER2/neu amplification status.

scholarly journals Prognostic values of L-type amino acid transporter 1 and CD98hc expression in breast cancer

2020 ◽  
pp. jclinpath-2020-206457
Author(s):  
Masaaki Ichinoe ◽  
Tetuo Mikami ◽  
Nobuyuki Yanagisawa ◽  
Tsutomu Yoshida ◽  
Kiyomi Hana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Invasive Breast Cancer ◽  
Poor Prognosis ◽  
Growth Factor Receptor ◽  
Amino Acid Transporter ◽  
Breast Cancers ◽  
Non Invasive ◽  
Invasive Tumour ◽  
Acid Transporter

AimsL-type amino acid transporter 1 (LAT1) is a major Na+-independent neutral amino acid transporter, forming a complex with CD98hc. The aim of this study is to investigate the significance of LAT1 and CD98hc in invasive breast cancer.MethodsLAT1 and CD98hc expression was immunohistochemically assessed in 280 invasive breast cancers and analysed for association with clinicopathological features.ResultsHigh levels of LAT1 and CD98hc were observed in triple-negative breast cancers (TNBCs) possessing negative immunoreactivity with oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, compared with non-TNBCs (NTNBCs), and were associated with lymph-node metastasis and higher nuclear grade. The high-LAT1-expression group showed a poor prognosis in NTNBC and TNBC, however, high-CD98hc-expression group showed a poor prognosis only in NTNBC. LAT1 and CD98hc expression could be the prognostic factors in univariate analyses, but not in multivariate analyses. Further, we found that invasive tumour components showed higher LAT1 and CD98hc expression than non-invasive tumour components.ConclusionsLAT1 and CD98hc may possess prognostic values in invasive breast cancer. LAT1 may be linked with cancer cell activities and disease progression in breast cancer.

scholarly journals Centromere 17 copy number gain reflects chromosomal instability in breast cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kyoungyul Lee ◽  
Hyun Jeong Kim ◽  
Min Hye Jang ◽  
Sejoon Lee ◽  
Soomin Ahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Copy Number ◽  
Chromosomal Instability ◽  
Copy Number Gain ◽  
Next Generation Sequencing Data ◽  
Her2 Status ◽  
Sequencing Data ◽  
Her2 Positive ◽  
Ki 67 ◽  
Positive Linear Correlation

AbstractChromosomal instability (CIN) is known to be associated with prognosis and treatment response in breast cancer. This study was conducted to determine whether copy number gain of centromere 17 (CEP17) reflects CIN, and to evaluate the prognostic and predictive value of CIN in breast cancer. CIN status was determined by summing copy number gains of four centromeric probes (CEP1, CEP8, CEP11, and CEP16) based on fluorescence in situ hybridization and CIN scores were calculated using next generation sequencing data. High CIN was associated with adverse clinicopatholgical parameters of breast cancer. Among them, positive HER2 status, high Ki-67 index and CEP17 copy number gain were found to be independent predictors of high CIN. High CIN was associated with poor clinical outcome of the patients in the whole group, as well as in luminal/HER2-negative and HER2-positive subtypes. CEP17 copy number was significantly higher in the high-CIN-score group than in the low-CIN-score group. A positive linear correlation between the mean CEP17 copy number and the CIN score was found. In conclusion, CEP17 copy number was confirmed as a useful predictor for CIN in breast cancer, and high CIN was revealed as an indicator of poor prognosis in breast cancer.

scholarly journals ER, PR, HER2, Ki-67 and CK5 in Early and Late Relapsing Breast Cancer—Reduced CK5 Expression in Metastases

2013 ◽  
Vol 7 ◽  
pp. BCBCR.S10701 ◽  
Author(s):  
Kristiina Joensuu ◽  
Marjut Leidenius ◽  
Mia Kero ◽  
Leif C. Andersson ◽  
Kathryn B. Horwitz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative ◽  
Significant Risk ◽  
Growth Factor Receptor ◽  
Primary Therapy ◽  
Breast Cancers ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B

Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression or occurrence in subgroups of breast cancers correlated with the time of recurrence. The expression of HER2, ER, PR, Ki-67, and CK5 was studied by IHC in 72 primary breast cancers and their corresponding recurrent/metastatic lesions. The patients were divided into three groups according to the time of the recurrence/metastasis: before two years, after 5 years, and after 10 years. Based on their IHC profiles, the tumors were divided into surrogates of the genetically defined subgroups of breast cancers and the subtype definitions were as follows: luminal A (ER or PR+HER2–), luminal B (ER or PR+HER2+), HER2 overexpressing (ER–PR–HER2+), triple-negative (ER–PR–HER2–), basal-like (ER–PR–HER2–CK5+), non-classified (ER–PR–HER2–CK5–) and luminobasal (ER or PR+CK5+). In multivariate analysis, tumor size and HER2 positivity were a significant risk of early cancer relapse. The metastases showed a significantly lower CK5 expression. CK5 positivity distinguished triple negative tumors into rapidly and slowly recurring cancers. The IHC subtype ER or PR+HER2– luminal A presented a significantly lower risk of early tumor recurrence. Ki-67 expression denoted early-relapsing tumors and correlated linearly with tumor progression, since Ki-67 positivity declined gradually from early-relapsing toward late-recurring cancers.

α-basic-crystallin expression in basal-like breast cancer and its association with brain metastasis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1025-1025
Author(s):  
H. F. Kennecke ◽  
D. Voduc ◽  
S. Leung ◽  
V. L. Cryns ◽  
C. M. Perou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Metastatic Disease ◽  
Distant Metastasis ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Chi Square ◽  
Ki 67 ◽  
Cancer Subtypes

1025 Background: Basal-like breast cancers are high grade tumors with poor prognosis, having propensity for brain and lung metastasis (Perou et al. Nature 406:747–52, 2000, Cheang et al. Clin Cancer Res 14:1368–76, 2008, Luck et al. Clin Oncol (R Coll Radiol) 20:40–5, 2008). α-basic-crystallin (αBC), a small heat shock protein with anti-apoptotic and oncogenic activity, is expressed in about half of basal-like breast cancers but only 6% of other types (Moyano et al. J Clin Invest 116:261–70, 2006). Here we investigate the association of αBC with sites of distant metastasis in a large cohort of breast cancer patients. Methods: Our cohort consists of 4046 early invasive breast cancers referred to the British Columbia Cancer Agency from 1986 to 1992. Archival paraffin tissue blocks were used to construct tissue microarrays. Breast cancer subtypes were defined using a surrogate of six immunohistochemical markers: ER, PR, HER2, Ki-67, epidermal growth factor receptor and cytokeratin 5/6. αBC immunostaining was scored by pre-established, published criteria. All documented sites of distant metastasis were abstracted by chart review according to predefined categories. The null hypothesis was tested using chi-square and Fisher's Exact tests; all tests were two-sided. Results: Among 3,248 cases with interpretable αBC data, 11% were αBC +. Among patients who developed distant metastatic disease, the 10-yr BCSS survival in αBC+ and - tumors was 12% and 29%. Sites of metastatic disease included: brain (15%), lung (35%), liver (35%) and bone (65%). Brain metastasis was significantly more common among αBC positive tumors (Fisher's Exact test p<10e-8). Basal-like tumors with brain metastasis commonly co-expressed αBC (Chi-square p=0.006). Conclusion: αBC is significantly associated with brain metastasis, particularly among basal breast cancers. These findings suggested that αBC may be involved in tumor cell metastasis and may allow early identification of a subset of patients at particularly high risk of brain metastasis. [Table: see text] No significant financial relationships to disclose.

Use of the ErbB2/CEP17 ratio to predict prognosis and response to trastuzumab-based therapy in the metastatic breast cancer setting

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11110-11110
Author(s):  
E. Fuchs ◽  
W. Köstler ◽  
R. Horvath ◽  
G. Hudelist ◽  
E. Kubista ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Copy Number ◽  
Metastatic Breast ◽  
Chromosome 17 ◽  
Fish Analysis ◽  
Significant Difference ◽  
Group A ◽  
Her 2

11110 Background: Despite patient selection based upon detection of Her-2/neu overexpression by immunohistochemistry (IHC) and/or presence of amplification of the Her-2/neu-encoding erbB2 oncogene measured by FISH, response to trastuzumab-based therapy is only achieved in a subset of patients with Her-2/neu overexpressing breast carcinomas. Exact quantification of erbB2 copy-number relative to chromosome 17 (CEP17) (ErbB2/CEP17 ratio “R”) probably adds further important predictive information. Methods: Clinical data of 137 patients receiving trastuzumab based treatment for Her-2/neu overexpressing (IHC) metastatic breast cancer were analysed. ErbB2/CEP17 ratio (R) was determined by quantitative FISH analysis in original tumor tissue using Vysis PathVysion DNA-based FISH technology. Results: ErbB2/CEP17 (R) provided additional predictive value for progression free survival (PFS) and time to first metastasis (TTM), but not for overall survival (OS) (all from start of trastuzumab containing treatment). The following cutoffs of Her-2/neu were identified: group A: 0–2.2 R (TTM: 49.8; OS: 6.7; PFS: 6.2); group B: 2.2- 6 R (TTM: 26.2; OS: 5.3; PFS: 9.3); group C: >6 CN (TTM: 20.1; OS: 3.9; PFS: 13.7) Kaplan-Maier analysis showed significant longer TTM for group A (p<0.01 vs. B/C), significant longer PFS for group C (p<0.01 vs. A/B). Significant differences in complete response (B/C: 16.9% vs C:44.4%), partial response (B/C: 20.2% vs. C: 33.3%) and progressive disease (B/C: 27% vs. 11.1%) were noted. No significant difference in overall survival between the groups was seen. Conclusions: ErbB/CEP17 R provides important prognostic information and, in metastatic patients, allows one to better predict response to trastuzumab-based treatment than the widely used binary classification of ErbB2 amplification that is based on a cut-off at a copy number of >2.2. No significant financial relationships to disclose.

Expression of androgen receptor and epidermal growth factor receptor in invasive breast cancer: A retrospective study of 1,438 patients from China.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12587-e12587
Author(s):  
Junqing Chen ◽  
Zhanhong Chen ◽  
Xiaojia Wang
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Retrospective Study ◽  
Androgen Receptor ◽  
Invasive Breast Cancer ◽  
Growth Factor Receptor ◽  
Ki 67 ◽  
Egfr Expression ◽  
Significant Difference ◽  
Epidermal Growth

e12587 Background: Triple-negative breast cancer (TNBC) is lack of clinically efficient targeted therapies and usually more aggressive with higher rate of distant metastasis and poor overall survival as compared with other breast cancer subtypes. Recent evidence demonstrates that androgen receptor (AR) and epidermal growth factor receptor (EGFR) are involved in the pathogenesis of TNBC. The aim of this study was to explore the expression of AR and EGFR in invasive breast cancer and evaluate the potential of AR and EGFR as biomarkers in TNBC. Methods: In this retrospective study, we analyzed 1438 patients with invasive breast cancer in our hospital from 2015 to 2016. Estrogen receptor (ER) expression, progesterone receptor (PR) expression, Ki-67 index, AR and EGFR expression were detected by immunohistochemical assay. HER2 state was determined by immunohistochemical and FISH assay. χ2 test was used for the analysis. Results: Among 1438 breast cancer patients, 272 (18.9%) cases were TNBC and 1165 (81.0%) cases were non-TNBC. TNBC patients had a low AR expression as compared with non-TNBC patients (29.8% vs 90.2%). There was a significant difference in AR expression in TNBC compared in non-TNBC ( P= 0.000). In contrast, TNBC patients had a high EGFR expression as compared with non-TNBC patients (90.9% vs 21.1%) ( P= 0.000). There was also a significant difference in Ki-67 index in TNBC compared in non-TNBC (89.9% vs 70.1%) ( P= 0.000). AR-positive TNBC patients had a low Ki-67 index expression as compared to AR-negative TNBC (82.7% vs 93.6%). No significant difference of EGFR expression was found between AR-positive TNBC and AR-negative TNBC. Conclusions: AR expression is associated with Ki-67 index and may be as a potential biomarker for targeted therapy in AR-positive TNBC patients.

Significance of chromosome 17 polysomy in breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12002-e12002
Author(s):  
Robert W. Galamaga ◽  
Rachel Mariani ◽  
Imad Almanaseer ◽  
Jacob D. Bitran
Keyword(s):  
Breast Cancer ◽  
Survival Data ◽  
Copy Number ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Chromosome 17 ◽  
Gene Copy ◽  
Breast Cancers ◽  
Her 2 ◽  
Disease Free

e12002 Background: Human epidermal growth factor receptor 2 (HER-2) overexpression occurs in up to 30% of breast cancers and has been associated with poor clinical outcomes that have improved with advances in HER-2 directed therapy. The HER-2 gene resides on the long arm of chromosome 17 and amplification is typically assessed via immunohistochemistry or fluorescence in situ hybridization (FISH); HER-2 is interpreted as amplified, non-amplified, or equivocal. The effect and clinical impact of chromosome 17 polysomy in specimens interpreted as HER-2 non-amplified has not been well-established in breast cancer patients. This subgroup may represent a unique set of patients who may benefit from HER-2 directed therapy given the increase in HER-2 gene copy number. If tumors with polysomy 17 share biologic similarities with those positive for HER-2 amplification this may significantly influence the approach to treating these patients. In a single institution study we reviewed all breast cancer cases diagnosed in 2008 which were reported as HER-2 equivocal or non-amplified via FISH and with chromosome 17 polysomy in order to extrapolate disease-free and overall survival data within this subset. Methods: HER-2 expression via FISH from patients diagnosed with breast cancer in 2008 was reviewed. In those patients with equivocal or non-amplified HER-2 expression we selected those with chromosome 17 polysomy defined as a chromosome 17 centromere copy number of > 3 per tumor cell. A total of 9 patients were identified. Results: The median age was 74 (36-88). Median tumor size was 1.6 cm (0.7-4.9) and 8 patients (88%) had both estrogen and progesterone positive tumors. Stage distribution was as follows: stage IA: 4 (44%); stage IIA: 2 (22%); stage IIB: 2 (22%) and stage IIIA: 1 (11%). The actuarial 3 year disease free survival was 67%. Conclusions: Breast cancers with equivocal or non-amplified HER-2 expression with chromosome 17 polysomy represent a unique subset of tumors with a biology that is not well-understood. Previously published studies have yielded conflicting results regarding the prognostic significance of this genotype. Our study reflects a three year survival of 67% which suggests that these patients represent an aggressive subset.

Isolated CEP17 Copy Number Gain in Invasive Breast Cancer Results in a “Reverse” Amplification Status

2020 ◽  
pp. 106689692091142
Author(s):  
Mieke R. Van Bockstal ◽  
Dominique Dubois ◽  
Stéphanie Talpe ◽  
Christine Galant
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Copy Number ◽  
Copy Number Gain

scholarly journals Quantifying tumour vascularity in non-luminal breast cancers

2017 ◽  
Vol 70 (9) ◽  
pp. 766-774 ◽  
Author(s):  
Maria Ryssdal Kraby ◽  
Signe Opdahl ◽  
Lars A Akslen ◽  
Anna M Bofin
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Proliferation Index ◽  
Breast Cancers ◽  
Basal Phenotype ◽  
Vascular Proliferation ◽  
Tumour Vascularity ◽  
Epidermal Growth ◽  
Von Willebrand ◽  
Willebrand Factor

AimsMicrovessel density (MVD), proliferating MVD (pMVD) and vascular proliferation index (VPI) are methods used to quantify tumour vascularity in histopathological sections. In this study, we assessed MVD, pMVD and VPI in non-luminal subtypes of breast cancer. Differences between subtypes were studied, and the prognostic value of each method was assessed.MethodsAll non-luminal subtypes (61 basal phenotype (BP), 60 human epidermal growth factor receptor 2 (HER2) type and 30 five negative phenotype (5NP)) were selected from a series comprising 909 cases of breast cancer. Sections were stained for Ki67 and von Willebrand factor. Associations between MVD, pMVD and VPI, molecular subtypes and prognosis were studied.ResultsMVD was highest in 5NP (Δ54.3 microvessels/mm2compared with BP, 95% CI 30.3 to 78.3), whereas no clear difference was found between HER2 type and BP (Δ8.8 microvessels/mm2, 95% CI −9.6 to 27.1). pMVD and VPI did not differ between subtypes. For MVD, HR was 1.07 (95% CI 1.03 to 1.11) per 10 vessel increase and 1.9 (95% CI 1.2 to 3.1) if MVD was greater than median value. High MVD was associated with poor prognosis in the HER2 type (HR 1.07 (95% CI 1.02 to 1.12)) and 5NP (HR 1.13 (95% CI 1.03 to 1.23)), but not in BP (HR 1.04 (95% CI 0.94 to 1.14) per 10 vessel increase). pMVD and VPI were not associated with prognosis.ConclusionsMVD appears to be an independent prognostic factor in HER2 and 5NP subtypes of breast cancer, where high MVD is associated with poor survival. MVD was higher in the 5NP compared with both BP and HER2 type.

scholarly journals 6q deletion is frequent but unrelated to patient prognosis in breast cancer

Breast Cancer ◽  
2021 ◽  
Author(s):  
Patrick Lebok ◽  
Hannah Bönte ◽  
Martina Kluth ◽  
Christina Möller-Koop ◽  
Isabell Witzel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Stage ◽  
Proliferation Index ◽  
Fish Analysis ◽  
Prognostic Impact ◽  
Advanced Tumor Stage ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Advanced Tumor ◽  
Frequent Event

Abstract Background Deletions involving the long arm of chromosome 6 have been reported to occur in breast cancer, but little is known about the clinical relevance of this alteration. Methods We made use of a pre-existing tissue microarray with 2197 breast cancers and employed a 6q15/centromere 6 dual-labeling probe for fluorescence in situ (FISH) analysis Results Heterozygous 6q15 deletions were found in 202 (18%) of 1099 interpretable cancers, including 19% of 804 cancers of no special type (NST), 3% of 29 lobular cancers, 7% of 41 cribriform cancers, and 28% of 18 cancers with papillary features. Homozygous deletions were not detected. In the largest subset of NST tumors, 6q15 deletions were significantly linked to advanced tumor stage and high grade (p < 0.0001 each). 6q deletions were also associated with estrogen receptor negativity (p = 0.0182), high Ki67 proliferation index (p < 0.0001), amplifications of HER2 (p = 0.0159), CCND1 (p = 0.0069), and cMYC (p = 0.0411), as well as deletions of PTEN (p = 0.0003), 8p21 (p < 0.0001), and 9p21 (p = 0.0179). However, 6q15 deletion was unrelated to patient survival in all cancers, in NST cancers, or in subsets of cancers defined by the presence or absence of lymph-node metastases. Conclusion Our data demonstrate that 6q deletion is a frequent event in breast cancer that is statistically linked to unfavorable tumor phenotype and features of genomic instability. The absence of any prognostic impact argues against a clinical applicability of 6q15 deletion testing in breast cancer patients.

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