Histamine H4 receptor expression in triple negative breast cancer.

DANIELA SPEISKY; MONICA TAQUEZ DELGADO; ALEJANDRO IOTT; IGNACIO OSPITAL; FELIX VIGOVICH; PABLO DEZANZO; GLENDA ERNST; JUAN LUIS URIBURU; VANINA A MEDINA

Hannover

Congreso; European Histamine Research Society 50th Annual Meeting; 2022

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype. There are neither universally accepted prognostic markers, nor molecular targets related to TNBC. The histamine H4 receptor (H4R) has been characterized in TNBC experimental models, demonstrating its critical role in tumor development and progression. In this study, the H4R expression was compared in breast cancer subtypes and correlated with clinical features using The Cancer Genome Atlas data (TCGA). The H4R status was further evaluated by immunohistochemistry in 30 TNBC human samples in relation to clinicopathological parameters. Analyses of TCGA Pan-Cancer Atlas data set show that H4R mRNA expression was lower in the aggressive basal-like/TNBC tumors compared with the more favorable clinical outcome luminal A subtype (P=0.028). A high level of H4R was significantly associated with improved relapse-free survival (HR 0.77, P=0.016) and overall survival (HR 0.64, P = 0.019) in basal-like cancer patients. To corroborate the bioinformatic analyses, we investigated the protein expression of H4R in TNBC samples, according to pathology-based classification. The specificity of the antibody was checked using HEK293 cells, which do not endogenously express H4R. Membranous and cytoplasmic H4R immunostaining was detected in about 70% of TNBC samples, and its expression was positively correlated with the levels in the histologically normal peritumoral tissue. High H4R expression in peritumoral tissue correlated with reduced number of lymph node involvement and unifocal TNBC while it was associated with increased patient survival. In conclusion, the H4R might represent a potential prognostic biomarker in TNBC, and a promising therapeutic target for this aggressive and difficult-to-treat type of breast cancer. Further studies in large cohorts are needed to better understand the significance of H4R in breast cancer biology.