title: Chromogenic in situ hybridization to detect HER-2/neu gene amplification in histological and ThinPrep-processed breast cancer fine-needle aspirates: a sensitive and practical method in the trastuzumab era.
abstract: The increasing evidence of trastuzumab efficacy in breast cancer (BC) patients means that an accurate and reproducible evaluation of HER-2 statusis of paramount importance in histological and in cytological samples. Currently, the two main methods used to analyze HER-2 amplification or overexpression are fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Although the two methods are strongly correlated for histological tissue, the evaluation of tumor morphology through FISH may be difficult and fluorescence fades quickly. These limitations can be overcome by chromogenic in situ hybridization (CISH), which can visualize the amplification product along with morphological features. In view of this, in the present study, we analyzed the usefulness of CISH on formalin-fixed, paraffin-embedded (FFPE) BC specimens and investigated whether CISH can be a valid technique in the determination of HER-2 status for fine-needle aspirates (FNAs) processed by liquid-based cytology. The results we obtained in a retrospective series of 111 FFPE BC specimens demonstrated good concordance between CISH and IHC and between CISH and FISH. The former concordance was comparable with that observed between FISH and IHC. When CISH was applied to a prospective series of 53 FNAs, from surgically removed BC, our data showed evidence of a higher concordance of results between liquid-based cytology and the companion FFPE tissues using CISH rather than HercepTesttrade mark. Therefore, CISH analysis, which is avaluable and reproducible alternative to FISH for selecting breast cancer patients for trastuzumab therapy, can lower false-positive immunocytochemistry findings in ThinPrep-processed FNAs.
authors.affiliation: Regina Elena Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy. vocaturo@ifo.it
authors.forename: Amina
authors.initials: A
authors.lastname: Vocaturo
authors.forename: Flavia
authors.initials: F
authors.lastname: Novelli
authors.forename: Maria
authors.initials: M
authors.lastname: Benevolo
authors.forename: Giulia
authors.initials: G
authors.lastname: Piperno
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Marandino
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Cianciulli
authors.forename: Roberta
authors.initials: R
authors.lastname: Merola
authors.forename: Raffaele Perrone
authors.initials: RP
authors.lastname: Donnorso
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Simonetta
authors.initials: S
authors.lastname: Buglioni
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D044963:Biopsy, Fine-Needle; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D002863:Chromogenic Compounds; D005260:Female; D005784:Gene Amplification; D016591:Histocytological Preparation Techniques; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D016612:Paraffin Embedding; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002863:Chromogenic Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab