Abstract
High affinity folate receptor (HFR) can be overexpressed in breast cancer and is associated with poor prognosis, however the expression in breast cancer brain metastases (BCBM) is unknown. The aim of this study was to analyze the rate of HFR expression in BCBM and its role in the prognosis of this high-risk cohort. We analyzed 19 brain metastasis (BM) and 13 primary tumors (PT) from a total of 25 patients. HFR status was assessed by immunohistochemistry. Median follow-up was 4.2 years (range 0.6-18.5). HFR was positive in 4/19 BM (21.1%) and in 1/13 PT (7.7%). Positive samples had low H-scores (range 1-50). 56% of patients had apocrine differentiation. OS was similar between patients with positive HFR (median OS 48 months) and negative HFR (median OS 69 months) (P = 0.25); and between patients with apocrine differentiation (median OS 63 months) and those without apocrine differentiation (median OS 69 months) (P = 0.49). To the best of our knowledge, this is the first analysis of HFR expression in BCBM. While previous studies associated the presence of HFR with worse prognosis; in our cohort HFR was positive in only 21.1% of BM with low levels of positivity. Neither HFR nor apocrine features had impact in OS.
Highlights
Folic acid is required by proliferating cells for the synthesis of nucleotide bases and methylation of DNA and proteins among other metabolic tasks
high affinity folate receptor (HFR) is overexpressed in 33% of primary tumors (PT) and this appeared to be associated with poor prognosis [11]
estrogen receptor (ER) and human epidermal growth factor 2 (HER2) were negative in 50% of cases, whereas progesterone receptor (PR) was negative in 72.7% of patients
Summary
Folic acid is required by proliferating cells for the synthesis of nucleotide bases and methylation of DNA and proteins among other metabolic tasks. The high affinity folate receptor (HFR) (Kd = 10-10 M) is a membrane protein that is upregulated in several cancers of epithelial origin and rarely present in most normal cells [3, 4]. High expression of HFR has been documented in ovarian, breast, kidney, uterine and lung cancers [3,4,5,6]. The expression levels of HFR have been associated with disease stage, aggressiveness and survival in ovarian cancer and in non-small cell lung cancer [5, 7,8,9,10]. HFR is overexpressed in 33% of primary tumors (PT) and this appeared to be associated with poor prognosis [11]. Analysis of the expression of HFR in triple-negative breast cancer (TNBC) has shown higher rates of positivity (50 – 80%) with worse prognosis for the HFR positive subgroup of patients [12,13,14]
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