title: Gene amplification in ductal carcinoma in situ of the breast.
abstract: Multiple different biologically and clinically relevant genes are often amplified in invasive breast cancer, including HER2, ESR1, CCND1, and MYC. So far, little is known about their role in tumor progression. To investigate their significance for tumor invasion, we compared pure ductal carcinoma in situ (DCIS) and DCIS associated with invasive cancer with regard to the amplification of these genes. Fluorescence in situ hybridization (FISH) was performed on a tissue microarray containing samples from 130 pure DCIS and 159 DCIS associated with invasive breast cancer. Of the latter patients, we analyzed the intraductal and invasive components separately. In addition, lymph node metastases of 23 patients with invasive carcinoma were included. Amplification rates of pure DCIS and DCIS associated with invasive cancer did not differ significantly (pure DCIS vs. DCIS associated with invasive cancer: HER2 22.7 vs. 24.2%, ESR1 19.0 vs. 24.1%, CCND1 10.0 vs. 14.8%, MYC 11.8 vs. 6.5%; P > 0.05). Furthermore, we observed a high concordance of the amplification status for all genes if in situ and invasive carcinoma of individual patients were compared. This applied also to the corresponding lymph node metastases. Our results indicate no significant differences between the gene amplification status of DCIS and invasive breast cancer concerning HER2, ESR1, CCND1, and MYC. Therefore, our data suggest an early role of all analyzed gene amplifications in breast cancer development but not in the initiation of invasive tumor growth.
authors.affiliation: Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Burkhardt
authors.forename: T J
authors.initials: TJ
authors.lastname: Grob
authors.forename: I
authors.initials: I
authors.lastname: Hermann
authors.forename: E
authors.initials: E
authors.lastname: Burandt
authors.forename: M
authors.initials: M
authors.lastname: Choschzick
authors.forename: F
authors.initials: F
authors.lastname: Jänicke
authors.forename: V
authors.initials: V
authors.lastname: Müller
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: R
authors.initials: R
authors.lastname: Simon
authors.forename: G
authors.initials: G
authors.lastname: Sauter
authors.forename: W
authors.initials: W
authors.lastname: Wilczak
authors.forename: A
authors.initials: A
authors.lastname: Lebeau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D019938:Cyclin D1 / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: D019938:Cyclin D1; D047628:Estrogen Receptor alpha; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; C530104:CCND1 protein, human; C506487:ESR1 protein, human; C489427:MYC protein, human; C508053:ERBB2 protein, human