80P Is there a link between crown-like structures and tumour-associated macrophages in patients with HER2+ breast cancer?

Abstract

Background: crown-like structures (CLS) are macrophages that surround enlarged or necrotic adipocytes. They are a marker of adipose tissue inflammation and have been associated with high body mass index (BMI) in breast cancer. Murine models have demonstrated that crosstalk within the inflammatory obese mammary tumour microenvironment causes increased macrophage recruitment into breast tumours when compared to lean counterparts. In this study, we investigated the association between the presence of CLS and changes in the density and phenotype of tumour-associated macrophages in patients with HER2+ breast cancer.

Methods: immunohistochemistry of 188 primary HER2+ tumours was performed for CLS, CD68, CD16 and CD32B macrophage markers. Definiens Architect XD Tissue Studio was used to automatically quantify macrophage density and phenotype. Descriptive statistical techniques were used to compare the differences in macrophage density by CLS status. The cut-off of CLS≤1 per full-face section was used to differentiate CLS low from CLS high.

Results: the density of CD68+ and CD68+CD16+ macrophages was found to be significantly higher in the tumour islands when compared to the stroma (adjusted p=0.002, p=0.006, respectively). The presence of CLS high in adipose tissue, border of the tumour or tumour islands (any-CLS) was significantly associated with BMI≥25 (adjusted p=0.03). The presence of any-CLS was significantly associated with a higher density of CD68+ macrophages in the stroma (adjusted p=0.018) and in the tumour as a whole (adjusted p=0.047) when compared to any-CLS low patients. There was also a trend for higher density of stromal CD68+CD16+ in the any-CLS high compared to the any-CLS low group, which was non-significant (adjusted p=0.099). CD16+CD32B+ CLS at the border of the tumour was not associated with a change in CD68+ or CD68+CD16+ macrophage density in the tumour islands, stroma or in the tumour as a whole (adjusted p>0.05).

Conclusions: the presence of any-CLS was associated with a significantly higher CD68+ macrophage density in the stroma and whole tumour in patients with HER2+ breast cancer.

More information

Identifiers

ORCID for C. Birts: orcid.org/0000-0002-0368-8766

ORCID for S. Beers: orcid.org/0000-0002-3765-3342

ORCID for C. Savva: orcid.org/0000-0003-0805-4719

Catalogue record

Export record

Altmetrics