title: Simultaneous fluorescence immunophenotyping and Her-2/neu genotyping (FICTION) in breast carcinoma candidates to target therapy.
abstract: The study of proto-oncogene Her-2/neu using the fluorescence in situ hybridization (FISH) technique in routinely paraffin-embedded formalin-fixed tissue has become commonplace over the past decade and mandatory among invasive breast cancer expressing a score 2+ by immunohistochemical analysis of c-erbB2 protein. The patient's eligibility for treatment with the biological drug trastuzumab/herceptin is based on the evidence of a Her-2/neu proto-oncogene amplification (ratio Her-2/neu/CEP-17>2.2). However, although the exclusion is declared in the absence of Her-2/neu gene amplification (ratio Her-2/neu/CEP-17 <1.8) according to the American Society of Clinical Oncology/College of American Pathologists recommendations, there are borderline cases (1.8<ratio Her-2/neu/CEP-17>2.2) that need to be investigated (eg, ductal carcinoma in situ with microinvasion, metastatic breast cancer). In such cases with Her-2/neu genetic heterogeneity it is difficult to count the nuclear signals in the areas of invasive tumor using fluorescence. The availability of a Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for Investigation of Neoplasms technique, based on the simultaneous evaluation of immunostaining with anticytokeratins (CKAE1/AE3 and CK19), together with FISH for Her-2/neu gene status [it is therefore useful and of current applicability in breast cancer blocks (formalin-fixed and paraffin-embedded)], permits a more easy identification of even single neoplastic cells by immunofluorescence and then a better evaluation of Her-2/neu status gene by the FISH technique, as shown in our study.
authors.affiliation: Second Department of Pathology, School of Medicine, University of Brescia, Brescia, Italy. l.benerini@virgilio.it
authors.forename: Luisa Benerini
authors.initials: LB
authors.lastname: Gatta
authors.forename: Paolo
authors.initials: P
authors.lastname: Incardona
authors.forename: Moris
authors.initials: M
authors.lastname: Cadei
authors.forename: Piergiovanni
authors.initials: P
authors.lastname: Grigolato
authors.forename: Sabrina
authors.initials: S
authors.lastname: Simoncelli
authors.forename: Piera
authors.initials: P
authors.lastname: Balzarini
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007633:Keratins / Q000378:metabolism; D058990:Molecular Targeted Therapy; D018579:Patient Selection; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007633:Keratins; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C000715470:MAS1 protein, human; C508053:ERBB2 protein, human