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

Journal of Experimental & Clinical Cancer Research

Franco Bonetti⁶  Guido Martignoni⁶  Keith Miller⁴  Giuseppe Zamboni¹  Marco Chilosi⁶  Serena Pedron⁶  Sara Cingarlini⁵  Giampaolo Tortora⁵  Francesco Massari⁵  Emilio Bria⁵  Annamaria Molino²  Marco Vergine³  Alessia Nottegar⁶  Erminia Manfrin⁶  Anna Caliò⁶  Giuseppe Bogina¹  Matteo Brunelli⁶  Eleonora Brunello⁶ 

[1] Ospedale Sacro Cuore, Negrar, Verona, Italy;Medical Oncology dO, Azienda Ospedaliera Universitaria Integrata, Verona, Italy;King’s College Hospital NHS Foundation Trust, London, United Kingdom;United Kingdom National External Quality Assessment Service (UKNeqas), London, United Kingdom;Medical Oncology dU, Azienda Ospedaliera Universitaria Integrata, Verona, Italy;Department of Pathology and Diagnostic, University of Verona, P.le Ludovico Scuro n. 10, Verona, 37134, Italy

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

Others  :  825547
DOI  :  10.1186/1756-9966-31-103

 received in 2012-11-14, accepted in 2012-12-20,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Brunello et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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