Open Access Research

FGFR-1 amplification in metastatic lymph-nodal and haematogenous lobular breast carcinoma

Eleonora Brunello1, Matteo Brunelli1*, Giuseppe Bogina2, Anna Caliò1, Erminia Manfrin1, Alessia Nottegar1, Marco Vergine3, Annamaria Molino4, Emilio Bria5, Francesco Massari5, Giampaolo Tortora5, Sara Cingarlini5, Serena Pedron1, Marco Chilosi1, Giuseppe Zamboni12, Keith Miller6, Guido Martignoni1 and Franco Bonetti1

Author Affiliations

1 Department of Pathology and Diagnostic, University of Verona, P.le Ludovico Scuro n. 10, Verona, 37134, Italy

2 Ospedale Sacro Cuore, Negrar, Verona, Italy

3 King’s College Hospital NHS Foundation Trust, London, United Kingdom

4 Medical Oncology dO, Azienda Ospedaliera Universitaria Integrata, Verona, Italy

5 Medical Oncology dU, Azienda Ospedaliera Universitaria Integrata, Verona, Italy

6 United Kingdom National External Quality Assessment Service (UKNeqas), London, United Kingdom

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Journal of Experimental & Clinical Cancer Research 2012, 31:103  doi:10.1186/1756-9966-31-103

Published: 27 December 2012

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.

Keywords:
Lobular breast carcinoma; Metastases; FGFR-1 amplification; In situ hybridization