title: Classical lobular breast carcinoma consistently lacks topoisomerase-IIα gene amplification: implications for the tailored use of anthracycline-based chemotherapies.
abstract: OBJECTIVE
  There is consistent lack of data focusing the topoisomerase-IIα gene status in lobular breast carcinoma, a subtype that usually shows poor responsiveness to chemotherapies including those using anthracycline drugs.
  
  
  RESULTS
  Forty-six infiltrative lobular carcinomas, 13 with matched metastases, were used. Topoisomerase-IIα gene amplification was evaluated by chromogenic in situ hybridization (CISH) and fluorescence in situ hybridization (FISH). We also assessed Her2/neu status by CISH, FISH and silver in situ hybridization (SISH). HER2 immunoexpression was assessed by the HercepTest. Forty-four of 46 (95%) cases revealed no topoisomerase-IIα amplification, whereas two of 46 (5%) cases were amplified by all three techniques. Eleven of the 13 metastatic sites showed no amplification either in the primary or in the metastases (85%); the remaining two were amplified (15%). Her2/neu was not amplified in 44 of 46 (95%) cases nor was it amplified in 11 of 13 (95%) metastatic tissues. The two cases showing Her2/neu and topoisomerase-IIα amplification scored 3+; the remaining non-amplified cases scored 0 or 1+ in 40 and 2+ in four cases.
  
  
  CONCLUSIONS
  In the era of personalized and tailored therapies, we suggest that patients affected by the classical lobular subtype of breast carcinoma constantly lack the ad hoc predictive rationale for receiving common chemotherapy that includes anthracyclines.
authors.affiliation: Department of Pathology and Diagnostic, University of Verona, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Brunello
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.forename: Erminia
authors.initials: E
authors.lastname: Manfrin
authors.forename: Alessia
authors.initials: A
authors.lastname: Nottegar
authors.forename: Samantha
authors.initials: S
authors.lastname: Bersani
authors.forename: Marco
authors.initials: M
authors.lastname: Vergine
authors.forename: Annamaria
authors.initials: A
authors.lastname: Molino
authors.forename: Elena
authors.initials: E
authors.lastname: Fiorio
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.forename: Stefano
authors.initials: S
authors.lastname: Gobbo
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.forename: Franco
authors.initials: F
authors.lastname: Bonetti
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D057285:Precision Medicine; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D018943:Anthracyclines; D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human