title: 8p deletion is strongly linked to poor prognosis in breast cancer.
abstract: Deletions of chromosome 8p occur frequently in breast cancers, but analyses of its clinical relevance have been limited to small patient cohorts and provided controversial results. A tissue microarray with 2,197 breast cancers was thus analyzed by fluorescence in-situ hybridization using an 8p21 probe in combination with a centromere 8 reference probe. 8p deletions were found in 50% of carcinomas with no special type, 67% of papillary, 28% of tubular, 37% of lobular cancers and 56% of cancers with medullary features. Deletions were always heterozygous. 8p deletion was significantly linked to advanced tumor stage (P < 0.0001), high-grade (P < 0.0001), high tumor cell proliferation (Ki67 Labeling Index; P < 0.0001), and shortened overall survival (P < 0.0001). For example, 8p deletion was seen in 32% of 290 grade 1, 43% of 438 grade 2, and 65% of 427 grade 3 cancers. In addition, 8p deletions were strongly linked to amplification of MYC (P < 0.0001), HER2 (P < 0.0001), and CCND1 (p = 0.001), but inversely associated with ER receptor expression (p = 0.0001). Remarkably, 46.5% of 8p-deleted cancers harbored amplification of at least one of the analyzed genes as compared to 27.5% amplifications in 8p-non-deleted cancers (P < 0.0001). In conclusion, 8p deletion characterizes a subset of particularly aggressive breast cancers. As 8p deletions are easy to analyze, this feature appears to be highly suited for future DNA based prognostic breast cancer panels. The strong link of 8p deletion with various gene amplifications raises the possibility of a role for regulating genomic stability.
authors.affiliation: a Institute of Pathology; University Medical Center Hamburg-Eppendorf ; Hamburg , Germany.
authors.forename: P
authors.initials: P
authors.lastname: Lebok
authors.forename: A
authors.initials: A
authors.lastname: Mittenzwei
authors.forename: M
authors.initials: M
authors.lastname: Kluth
authors.forename: C
authors.initials: C
authors.lastname: Özden
authors.forename: B
authors.initials: B
authors.lastname: Taskin
authors.forename: K
authors.initials: K
authors.lastname: Hussein
authors.forename: K
authors.initials: K
authors.lastname: Möller
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
authors.forename: A
authors.initials: A
authors.lastname: Lebeau
authors.forename: I
authors.initials: I
authors.lastname: Witzel
authors.forename: S
authors.initials: S
authors.lastname: Mahner
authors.forename: L
authors.initials: L
authors.lastname: Wölber
authors.forename: F
authors.initials: F
authors.lastname: Jänicke
authors.forename: S
authors.initials: S
authors.lastname: Geist
authors.forename: P
authors.initials: P
authors.lastname: Paluchowski
authors.forename: C
authors.initials: C
authors.lastname: Wilke
authors.forename: U
authors.initials: U
authors.lastname: Heilenkötter
authors.forename: R
authors.initials: R
authors.lastname: Simon
authors.forename: G
authors.initials: G
authors.lastname: Sauter
authors.forename: L
authors.initials: L
authors.lastname: Terracciano
authors.forename: R
authors.initials: R
authors.lastname: Krech
authors.forename: A
authors.initials: A
authors.lastname: von der Assen
authors.forename: V
authors.initials: V
authors.lastname: Müller
authors.forename: E
authors.initials: E
authors.lastname: Burandt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: D019938:Cyclin D1; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; C530104:CCND1 protein, human
keywords: 8p; ER, estrogen receptor; FISH; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; Ki67LI, Ki67 Labeling index; LOH, loss of heterozygosity; NGS, next generation sequencing; NST, no special type; PR, progesterone receptor; TMA, tissue microarray; breast cancer; deletion; pN, nodal stage; pT, pathological tumor stage; prognosis