Abstract P6-17-06: Relevance of the hyaluronidase-1 (HYAL1) in brain metastasis formation of breast cancer patients

Abstract

Abstract The incidence of brain metastases in breast cancer (BMBC) patients has increased in the last years and represents the major life-limiting problem for metastatic breast cancer (BC) patients. However, the knowledge about tumor cell invasion in the brain is still very limited and new markers for brain metastasis incidence are urgently needed in order to early detect high risk patients. In a recent study based on cDNA microarray data of primary breast tumors, we could show that mRNA expression of certain glycosylation enzymes significantly correlates with an organ-specific metastatic spread. Interestingly, hyaluronan synthase 2 (HAS2) and hyaluronidase-1 (HYAL1), both genes involved in hyaluronan (HA) metabolism, showed an independent prognostic value and a significant correlation with brain metastasis formation. In order to corroborate the role of these enzymes at protein level, we examined the expression of HYAL1 and HAS2 on a tissue microarray including 200 primary BC samples. Here, the prognostic impact of HAS2 could not be validated, whereas for HYAL1 shorter disease free survival (DFS) was observed for patients with high HYAL1-expression levels. This trend could be additionally verified in a second cohort of 107 BC samples, using western blot analysis. Moreover, significantly higher HYAL1 expression was detected among primary tumors with subsequent brain metastases compared with those without brain metastases using immunohistochemistry (IHC). No impact of HYAL1 expression on disease progression of BCBM patients could be observed after analysis of 87 brain metastasis samples. Here, quantification of tumor-associated HA revealed a significant positive correlation with triple negative tumors and a trend towards shorter progression-free survival. Taken together, our data suggest a role of the enzyme HYAL1 for progression and especially for the development of brain metastases in breast cancer patients. Citation Format: Oliveira-Ferrer L, Anna M, Wickman H, Matschke J, Schumacher U, Milde-Langosch K, Müller V, Witzel I. Relevance of the hyaluronidase-1 (HYAL1) in brain metastasis formation of breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-17-06.