Evaluation of Tissue Expression of HMBG1 Protein in Patients With Breast Cancer

High mobility group box 1 (HMGB1) is a nonhistone chromatin-associated protein involved in chromatin remodeling, transcription, DNA replication, and repair. The purpose of this study was to assess the relationship between tissue expression of HMGB1, clinical outcomes, and histopathological characteristics in patients with breast cancer.

The study included 282 patients with breast cancer. An in vitro diagnostic HMGB1 antibody was applied to the slides of tumor specimens.

Overexpression of HMGB1 was found in tumor cells of 123 (43.6%) patients. HMGB1 was only expressed in the nucleus in most tumors (88.7%), while in 32 (11.3%) tumors HMBG1 expression was cytoplasmic and/or extracellular. Severe inflammatory infiltration of the peritumoral stroma was observed in 76 (27%) patients. There was a correlation between remarkable inflammatory cell infiltration in the tumor microenvironment and HMGB1 overexpression, regardless of the molecular subtype, as well as the extranuclear location of HMGB1 expression (p = 0.023). HMGB1 expression was not found to be associated with overall or disease-free survival. However, axillary lymph node metastasis was significantly more common in tumors with intense inflammation (p = 0.024).

The proportion of breast cancer patients with HMGB1 expression was lower in the present study than that reported previously. Furthermore, we did not detect a relationship between HMGB1 expression and prognosis. However, the relationship between HMGB1 expression and prognosis had been previously reported only in aggressive breast cancers. It is suggested that understanding the significance of HMGB1 expression in breast cancer may open new treatment opportunities, especially in aggressive and/or triple negative tumors.