Multiplication of Chromosome 17 Centromere Is Associated with Prognosis in Patients with Invasive Breast Cancers Exhibiting Normal HER2 and TOP2A Status

Overview

Journal J Breast Cancer

Date 2012 Apr 12

PMID 22493625

Citations 10

Authors

Aeri Kim

Hyung Chan Shin

Young Kyung Bae

Min Kyoung Kim

Su Hwan Kang

Soo Jung Lee

Eun Hee Lee

Affiliations

Soon will be listed here.

Abstract

Purpose: This study aimed to investigate the clinical significance of chromosome 17 centromere (CEP17) multiplication (increased copy number of CEP17) related to human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) status in patients with invasive breast cancer.

Methods: We constructed tissue microarrays using 594 invasive breast cancer samples and performed single-color silver-enhanced in situ hybridization (SISH) assay for HER2, TOP2A, and CEP17 to assess for copy number aberrations. The association of CEP17 multiplication with patient survival was analyzed according to HER2 and TOP2A status.

Results: Among 567 informative cases, HER2 amplification was noted in 22.8%, TOP2A amplification in 8.3% and TOP2A deletion in 11.1%. CEP17 multiplication was identified in 33.2% and was significantly associated with worse overall survival (OS) (p=0.02) and disease-free survival (DFS) (p=0.02). CEP17 multiplication correlated with patient survival in patients with normal TOP2A or non-amplified HER2 status, but the prognostic significance was lost in those with altered TOP2A or amplified HER2. On multivariate analyses, CEP17 multiplication was an independent prognostic factor for poorer OS (p=0.02) and DFS (p=0.01) in patients with normal TOP2A and non-amplified HER2.

Conclusion: CEP17 multiplication was identified as a promising prognostic marker in patients with invasive breast cancer exhibiting either non-amplified HER2 or normal TOP2A status.

Citing Articles

Patterns of Chromosomal Instability and Clonal Heterogeneity in Luminal B Breast Cancer: A Pilot Study.

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PMID: 38674062 PMC: 11049937. DOI: 10.3390/ijms25084478.

Impact of chromosome 17 centromere copy number increase on patient survival and human epidermal growth factor receptor 2 expression in gastric adenocarcinoma.

Ciesielski M, Szajewski M, Walczak J, Peksa R, Lenckowski R, Supel M Oncol Lett. 2021; 21(2):142.

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Centromere 17 copy number gain reflects chromosomal instability in breast cancer.

Lee K, Kim H, Jang M, Lee S, Ahn S, Park S Sci Rep. 2019; 9(1):17968.

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HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation.

Ahn S, Woo J, Lee K, Park S J Pathol Transl Med. 2019; 54(1):34-44.

PMID: 31693827 PMC: 6986968. DOI: 10.4132/jptm.2019.11.03.

Copy number variation and high expression of DNA topoisomerase II alpha predict worse prognosis of cancer: a meta-analysis.

Ren L, Liu J, Gou K, Xing C J Cancer. 2018; 9(12):2082-2092.

PMID: 29937926 PMC: 6010676. DOI: 10.7150/jca.23681.

References

Bartlett J, Munro A, Dunn J, McConkey C, Jordan S, Twelves C . Predictive markers of anthracycline benefit: a prospectively planned analysis of the UK National Epirubicin Adjuvant Trial (NEAT/BR9601). Lancet Oncol. 2010; 11(3):266-74. DOI: 10.1016/S1470-2045(10)70006-1. View

Knoop A, Knudsen H, Balslev E, Rasmussen B, Overgaard J, Nielsen K . retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil:.... J Clin Oncol. 2005; 23(30):7483-90. DOI: 10.1200/JCO.2005.11.007. View

Gennari A, Sormani M, Pronzato P, Puntoni M, Colozza M, Pfeffer U . HER2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials. J Natl Cancer Inst. 2007; 100(1):14-20. DOI: 10.1093/jnci/djm252. View

Mukherjee A, Shehata M, Moseley P, Rakha E, Ellis I, Chan S . Topo2α protein expression predicts response to anthracycline combination neo-adjuvant chemotherapy in locally advanced primary breast cancer. Br J Cancer. 2010; 103(12):1794-800. PMC: 3008601. DOI: 10.1038/sj.bjc.6605960. View

Krishnamurti U, Hammers J, Atem F, Storto P, Silverman J . Poor prognostic significance of unamplified chromosome 17 polysomy in invasive breast carcinoma. Mod Pathol. 2009; 22(8):1044-8. DOI: 10.1038/modpathol.2009.61. View

Burgess D, Doles J, Zender L, Xue W, Ma B, McCombie W . Topoisomerase levels determine chemotherapy response in vitro and in vivo. Proc Natl Acad Sci U S A. 2008; 105(26):9053-8. PMC: 2435590. DOI: 10.1073/pnas.0803513105. View

Jarvinen T, Liu E . HER-2/neu and topoisomerase IIalpha in breast cancer. Breast Cancer Res Treat. 2003; 78(3):299-311. DOI: 10.1023/a:1023077507295. View

Elston C, Ellis I . Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991; 19(5):403-10. DOI: 10.1111/j.1365-2559.1991.tb00229.x. View

Jarvinen T, Tanner M, Rantanen V, Barlund M, Borg A, Grenman S . Amplification and deletion of topoisomerase IIalpha associate with ErbB-2 amplification and affect sensitivity to topoisomerase II inhibitor doxorubicin in breast cancer. Am J Pathol. 2000; 156(3):839-47. PMC: 1876829. DOI: 10.1016/s0002-9440(10)64952-8. View

10.

Jarvinen T, Tanner M, Barlund M, Borg A, Isola J . Characterization of topoisomerase II alpha gene amplification and deletion in breast cancer. Genes Chromosomes Cancer. 1999; 26(2):142-50. View

11.

Hammond M, Hayes D, Dowsett M, Allred D, Hagerty K, Badve S . American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010; 28(16):2784-95. PMC: 2881855. DOI: 10.1200/JCO.2009.25.6529. View

12.

Dhesy-Thind B, Pritchard K, Messersmith H, OMalley F, Elavathil L, Trudeau M . HER2/neu in systemic therapy for women with breast cancer: a systematic review. Breast Cancer Res Treat. 2007; 109(2):209-29. DOI: 10.1007/s10549-007-9656-y. View

13.

Pritchard K, Shepherd L, OMalley F, Andrulis I, Tu D, Bramwell V . HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med. 2006; 354(20):2103-11. DOI: 10.1056/NEJMoa054504. View

14.

Konecny G, Pauletti G, Untch M, Wang H, Mobus V, Kuhn W . Association between HER2, TOP2A, and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer. Breast Cancer Res Treat. 2010; 120(2):481-9. DOI: 10.1007/s10549-010-0744-z. View

15.

Viale G . Be precise! The need to consider the mechanisms for CEP17 copy number changes in breast cancer. J Pathol. 2009; 219(1):1-2. DOI: 10.1002/path.2593. View

16.

Jung K, Park S, Kong H, Won Y, Boo Y, Shin H . Cancer statistics in Korea: incidence, mortality and survival in 2006-2007. J Korean Med Sci. 2010; 25(8):1113-21. PMC: 2908777. DOI: 10.3346/jkms.2010.25.8.1113. View

17.

Slamon D, Press M . Alterations in the TOP2A and HER2 genes: association with adjuvant anthracycline sensitivity in human breast cancers. J Natl Cancer Inst. 2009; 101(9):615-8. DOI: 10.1093/jnci/djp092. View

18.

Dietel M, Ellis I, Hofler H, Kreipe H, Moch H, Dankof A . Comparison of automated silver enhanced in situ hybridisation (SISH) and fluorescence ISH (FISH) for the validation of HER2 gene status in breast carcinoma according to the guidelines of the American Society of Clinical Oncology and the College of.... Virchows Arch. 2007; 451(1):19-25. DOI: 10.1007/s00428-007-0424-5. View

19.

Cardoso F, Durbecq V, Larsimont D, Paesmans M, Leroy J, Rouas G . Correlation between complete response to anthracycline-based chemotherapy and topoisomerase II-alpha gene amplification and protein overexpression in locally advanced/metastatic breast cancer. Int J Oncol. 2003; 24(1):201-9. View

20.

Wolff A, Hammond M, Schwartz J, Hagerty K, Allred D, Cote R . American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2006; 25(1):118-45. DOI: 10.1200/JCO.2006.09.2775. View