Marcin Braun, Jakub Czerwiński, Julia Richert, Julia Sołek, Dominik Paprocki, Tomasz Labuk, Michał Maj, Cecilia Analia Panek, Dominika Piasecka, Joanna Zofia Chrobak-Bień, Dariusz Nejc, Agnieszka Wanda Piastowska-Ciesielska, Radzisław Kordek, Natalia Bednarz-Knoll, Rafal Sadej, Hanna Romanska
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.
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.