Fibroblast growth factor receptor 1 status discordance between primary breast tumours and lymph node metastases is associated with peripheral blood circulating tumour cell burden.

INTRODUCTION

Fibroblast growth factor receptor (FGFR) signalling is implicated in breast cancer (BC) progression, but little is known about FGFR status as the disease develops. We evaluated FGFR1-4 expression changes in primary tumours (PT) and matched lymph node metastases (LNM) in the context of BC phenotype and circulating tumour cell (CTC) burden.

MATERIAL AND

METHODS

Fibroblast growth factor receptor 1-4, oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2) and Ki-67 were assessed immunohistochemically in paired PT and LNM. Circulating tumour cells were quantified by imaging flow cytometry in 67 BC patients and correlated with BC phenotype and FGFR status.

RESULTS

Switch of the BC subtype between PT and LNM was observed in 3/23 cases (13.0%). In contrast, discordance in FGFR expression occurred in 11/22 (50.0%), 5/22 (22.7%), 12/22 (54.5%), and 5/21 (23.8%) cases for FGFR1, FGFR2, FGFR3, and FGFR4, respectively; in most discordant cases, the difference reflected increased expression in LNM. Circulating tumour cells were detected in 22/67 patients (32.8%), with a median burden of 5.7 CTCs per 1 million peripheral blood mononuclear cells (interquartile ranges: 3.0-17.8). Circulating tumour cell presence was not associated with lymph node (LN) status (p = 0.806). Circulating tumour cell presence was more frequent in cases with FGFR1 discordance than in FGFR1-concordant tumours (63.6% vs. 9.1%; p = 0.024). Circulating tumour cell burden correlated inversely with FGFR1 level in LNM (Spearman's ρ = -0.49, p = 0.021). A shift in the FGFR1 status was noted exclusively in HER2-negative tumours.

CONCLUSIONS

The observed association between CTCs and FGFR1 status conversion, but not LN involvement in the context of disease progression, may reflect a previously unrecognised biological feature of FGFR1- positive cells, most likely restricted to HER2-negative breast cancer.