title: FGFR-1 amplification in metastatic lymph-nodal and haematogenous lobular breast carcinoma.
abstract: BACKGROUND
  Lobular breast carcinoma usually shows poor responsiveness to chemotherapies and often lacks targeted therapies. Since FGFR1 expression has been shown to play pivotal roles in primary breast cancer tumorigenesis, we sought to analyze the status of FGFR1 gene in a metastatic setting of lobular breast carcinoma, since promising FGFR1 inhibitors has been recently developed.
  
  
  METHODS
  Fifteen tissue metastases from lobular breast carcinomas with matched primary infiltrative lobular breast carcinoma were recruited. Eleven cases showed loco-regional lymph-nodal and four haematogenous metastases.FGFR-1 gene (8p12) amplification was evaluated by chromogenic in situ hybridization (CISH) analysis. Her-2/neu and topoisomerase-IIα gene status was assessed. E-cadherin and Hercept Test were also performed. We distinguished amplification (>6 or cluster of signals) versus gains (3-6 signals) of the locus specific FGFR-1 gene.
  
  
  RESULTS
  Three (20%) primary lobular breast carcinomas showed >6 or cluster of FGFR1 signals (amplification), six cases (40%) had a mean of three (range 3-6) chromogenic signals (gains) whereas in 6 (40%) was not observed any abnormality. Three of 15 metastasis (20%) were amplified, 2/15 (13,4%) did not. The ten remaining cases (66,6%) showed three chromogenic signals.The three cases with FGFR-1 amplification matched with those primary breast carcinomas showing FGFR-1 amplification. The six cases showing FGFR-1 gains in the primary tumour again showed FGFR-1 gains in the metastases. Four cases showed gains of FGFR-1 gene signals in the metastases and not in the primary tumours. Her-2/neu gene amplification was not observed in all cases but one (6%) case. Topoisomerase-IIα was not amplified in all cases.
  
  
  CONCLUSIONS
  1) a subset of metastatic lobular breast carcinoma harbors FGFR-1 gene amplification or gains of chromogenic signals; 2) a minor heterogeneity has been observed after matching primary and metastatic carcinomas; 3) in the era of tailored therapies, patients affected by the lobular subtype of breast carcinoma with FGFR1 amplification could be approached to the new target biological therapy such as emerging FGFR-1 inhibitors.
authors.affiliation: Department of Pathology and Diagnostic, University of Verona, Verona, 37134, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Brunello
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bogina
authors.forename: Anna
authors.initials: A
authors.lastname: Caliò
authors.forename: Erminia
authors.initials: E
authors.lastname: Manfrin
authors.forename: Alessia
authors.initials: A
authors.lastname: Nottegar
authors.forename: Marco
authors.initials: M
authors.lastname: Vergine
authors.forename: Annamaria
authors.initials: A
authors.lastname: Molino
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.forename: Sara
authors.initials: S
authors.lastname: Cingarlini
authors.forename: Serena
authors.initials: S
authors.lastname: Pedron
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zamboni
authors.forename: Keith
authors.initials: K
authors.lastname: Miller
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.forename: Franco
authors.initials: F
authors.lastname: Bonetti
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; 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; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015820:Cadherins; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; C508053:ERBB2 protein, human; C496348:FGFR1 protein, human