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Comparison of liquid based cytology and histology for the evaluation of HER-2 status using immunostaining and CISH in breast carcinoma

¹ Laboratoire Pol Bouin, Centre Hospitalier et Universitaire de Reims, 45, Rue Cognacq-Jay, 51092 Reims Cedex, France
² Institut Godinot Reims, 1 rue du Général Koenig, 51100 Reims, France
³ Service de Gynécologie Obstétrique, Centre Hospitalier et Universitaire de Reims
⁴ Service Cytogénétique, Centre Hospitalier et Universitaire de Reims
⁵ Unité INSERM U514, rue Cognacq Jay, 51092 Reims, France

Correspondence to:
Dr H Sartelet
Laboratoire d’Histologie, Faculté de Médecine, 51, Rue Cognacq-Jay, 51095 Reims Cedex, France; hsartelet{at}chu-reims.fr Background: HER-2 amplification is an important prognostic biomarker and treatment determinant in breast carcinoma.

Aims: To correlate immunocytochemical (ICC) expression of HER-2 and gene amplification determined by chromogenic in situ hybridisation (CISH) using liquid based cytology (LBC) with immunohistochemistry (IHC) and CISH using histological samples of the same breast carcinomas.

Methods: Frozen sections and cytobrushings of 103 breast carcinomas were analysed. Four techniques were performed on each tumour: two on LBC samples (ICC, and CISH, both graded as positive, indeterminate, or negative) and two on histological samples (IHC and CISH). Two cell lines (MCF-7, negative; BT 474, positive) were used as controls for cytological analysis. A complementary fluorescence in situ hybridisation technique was carried out in histological samples with low amplification (4–10 dots/nucleus).

Results: Interobserver agreement for the four techniques calculated by the coefficient indicated a substantial agreement. Nine cases failed in cytology because of poor cellularity. Among 94 cases, 19 were amplified; 73, 12, and 9 tumours were scored 0 or 1+, 2+, and 3+, respectively by IHC and 75, 13, and 6, respectively, by ICC. CISH found no amplification in 72 tumours. Correlations between the IHC and CISH results in the histological and cytological samples were always significant.

Conclusions: Her-2 status could be determined in LBC samples and correlated well with reference histological methods using in situ hybridisation. ICC was less reliable because of the presence of the cytoplasmic membrane. However, these results should be confirmed by a large multicentre study.

Abbreviations: CI, confidence interval; CISH, chromogenic in situ hybridisation; FISH, fluorescence in situ hybridisation; ICC, immunocytochemical; IHC, immunohistochemistry; LBC, liquid based cytology; SSC, standard saline citrate

Keywords: Her-2; breast cancer; liquid based cytology; chromogenic in situ hybridisation; fluorescence in situ hybridisation; immunohistochemistry; immunocytochemistry

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