Abstract
AimsBreast cancer (BC) is the most frequent tumour in women, representing 20–30% of all malignancies, and continues to be the leading cause of cancer deaths among European women. Triple-negative (TN) BC biological aggressiveness is associated with a higher dissemination rate, with central nervous system (CNS) metastases common. This study aims to elucidate the association between gene expression profiles of PTGS2, HBEGF and ST6GALNAC5 and the development of CNS metastases in TNBC.MethodsThis is a case-controlled retrospective study comparing patients (pts) with CNS metastases versus patients without them after adjuvant treatment. The selection of the samples was performed including 30 samples in both case and control groups. Formalin-fixed, paraffin-embedded samples were retrieved from the Hospital 12 de Octubre Biobank. Five 10 µm sections from each FFPE sample were deparaffinised with xylene and washed with ethanol, and the RNA was then extracted with the RecoverAll Kit (Ambion). Gene expression was assessed using TaqMan assays.ResultsA total of 53 patients were included in the study. The average age was 55 years (range 25–85). About 47 patients (88.67%) had ductal histology and presented high grade (III) tumours (40 patients; 75.47%). Eight women in the case group presented first distant recurrence in the CNS (34.80%), local recurrence (three patients, 13.04%), lungs (two patients; 8.7%), bone (one patient; 4.34%) and other locations (seven patients; 30.38%). In the control group, first distant recurrence occurred locally (six patients; 46.1%), in bone (two patients; 15.4%), lungs (one patient; 7.7%) and other sites (four patients; 23.1%). RNA was successfully obtained from 53 out of 60 samples. PTGS2, HBEGF, and ST6GALNAC5 expression values were not related to metastasis location.ConclusionTN tumours frequently metastasise to the visceral organs, particularly lungs and brain, and are less common in bone. The literature suggests that expression of the three genes of interest (PTGS2, HBEGF, and ST6GALNAC5) could be different in TNBC patients with CNS metastasis when compared to patients without it. We did not find a differential expression pattern in PTGS2, HBEGF, and ST6GALNAC5 genes in primary TNBC showing CNS metastases. Further studies are needed to clarify the role of these genes in CNS metastases in TNBC patients.
Highlights
The incidence of breast cancer (BC) is increasing [1] and has displaced cardiovascular pathology as the leading cause of mortality among women in the Western world
The literature suggests that expression of the three genes of interest (PTGS2, HBEGF, and ST6GALNAC5) could be different in TNBC patients with central nervous system (CNS) metastasis when compared to patients without it
Further studies are needed to clarify the role of these genes in CNS metastases in TNBC patients
Summary
The incidence of breast cancer (BC) is increasing [1] and has displaced cardiovascular pathology as the leading cause of mortality among women in the Western world. The triple negative (TN) BC subtype represents approximately 10–20% of all cases of BC in Caucasian women It characteristically affects young women, is associated with poor prognosis pathological characteristics, high rates of early tumoural relapse, high rates of visceral metastasis (20–30%, lung and brain), short survival and the absence of targeted biological therapy. Genetic expression studies based on studies of levels of mRNA such as the PAM50 (RT-PCR) assay [11] have identified at least four molecular subtypes of BC with different clinical behaviour: Luminal A, luminal B, HER2 and basal-like [4]. We will analyse the expression of three genes of interest (PTGS2, HBEGF, and ST6GALNAC5) in the FFPE tissue of primary TN phenotype breast tumours with CNS metastasis compared to patients who do not present with cerebral metastasis
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