title: Prognostic significance of centromere 17 copy number gain in breast cancer depends on breast cancer subtype.
abstract: Increased copy number of chromosome enumeration probe (CEP) targeting centromere 17 is frequently encountered during HER2 in situ hybridization (ISH) in breast cancer. The aim of this study was to clarify the clinicopathologic significance of CEP17 copy number gain in a relatively large series of breast cancer patients. We analyzed 945 cases of invasive breast cancers whose HER2 fluorescence ISH reports were available from 2004 to 2011 at a single institution and evaluated the association of CEP17 copy number gain with clinicopathologic features of tumors and patient survival. We detected 186 (19.7%) cases of CEP17 copy number gain (CEP17≥3.0) among 945 invasive breast cancers. In survival analysis, CEP17 copy number gain was not associated with disease-free survival of the patients in the whole group. Nonetheless, it was found to be an independent adverse prognostic factor in the HER2-negative group but not in the HER2-positive group. In further subgroup analyses, CEP17 copy number gain was revealed as an independent poor prognostic factor in HER2-negative and hormone receptor-positive breast cancers, and it was associated with aggressive histologic variables including high T stage, high histologic grade, lymphovascular invasion, p53 overexpression, and high Ki-67 proliferative index. In conclusion, we found that elevated CEP17 count can serve as a prognostic marker in luminal/HER2-negative subtype of invasive breast cancer. We advocate the use of the dual-colored fluorescence ISH using CEP17 rather than the single-colored one because it gives additional valuable information on CEP17 copy number alterations.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Pathology, Kangwon National University Hospital, Chuncheon, Kangwon 24289, Republic of Korea.
authors.forename: Kyuongyul
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Pathology, Yeungnam University Medical Center, Daegu 42415, Republic of Korea.
authors.forename: Min Hye
authors.initials: MH
authors.lastname: Jang
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
authors.forename: Yul Ri
authors.initials: YR
authors.lastname: Chung
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620, Republic of Korea.
authors.forename: Yangkyu
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Breast Care Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620, Republic of Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Kang
authors.affiliation: Breast Care Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620, Republic of Korea.
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Breast Care Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620, Republic of Korea.
authors.forename: Yu Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Breast Care Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620, Republic of Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Breast Care Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620, Republic of Korea.
authors.forename: In Ah
authors.initials: IA
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620, Republic of Korea; Breast Care Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620, Republic of Korea. Electronic address: sypmd@snu.ac.kr.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002503:Centromere / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D056915:DNA Copy Number Variations; D018572:Disease-Free Survival; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008408:Mastectomy; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D056910:Republic of Korea; D013997:Time Factors; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Breast cancer; Centromere 17; Copy number gain; HER2; Prognosis; Subtype; in situ hybridization