Varying outcomes of triple-negative breast cancer in different age groups-prognostic value of clinical features and proliferation.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive disease lacking specific biomarkers to guide treatment decisions. We evaluated the combined prognostic impact of clinical features and novel biomarkers of cell cycle-progression in age-dependent subgroups of TNBC patients.

Methods: One hundred forty seven TNBC patients with complete clinical data and up to 18 year follow-up were collected from Turku University Hospital, Finland.

GIT1 protects against breast cancer growth through negative regulation of Notch.

Hyperactive Notch signalling is frequently observed in breast cancer and correlates with poor prognosis. However, relatively few mutations in the core Notch signalling pathway have been identified in breast cancer, suggesting that as yet unknown mechanisms increase Notch activity. Here we show that increased expression levels of GIT1 correlate with high relapse-free survival in oestrogen receptor-negative (ER(-)) breast cancer patients and that GIT1 mediates negative regulation of Notch.

Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity.

ISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we use a virus-like particle trapping technology to identify ISG15-binding proteins and discover Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder.

A prognostic model based on cell-cycle control predicts outcome of breast cancer patients.

Background: A prognostic model combining biomarkers of metaphase-anaphase transition of the cell cycle was developed for invasive breast cancer. The prognostic value and clinical applicability of the model was evaluated in comparison with the routine prognosticators of invasive breast carcinoma.

Methods: The study comprised 1135 breast cancer patients with complete clinical data and up to 22-year follow-up.

Tumor-infiltrating lymphocytes and CD8 T cells predict survival of triple-negative breast cancer.

Purpose: Tumor inflammatory response was evaluated as a prognostic feature in triple-negative breast cancer (TNBC) and compared with the clinical prognosticators of breast cancer and selected biomarkers of cancer cell proliferation.

Methods: TNBC patients (n = 179) with complete clinical data and up to 18-year follow-up were obtained from Auria biobank, Turku University Hospital, Turku, Finland. Tumor-infiltrating lymphocytes (TILs) and several subtypes of inflammatory cells detected with immunohistochemistry were evaluated in different tumor compartments in full tissue sections and tissue microarrays.