Homeodomain-interacting Protein Kinase 1 (HIPK1) Expression in Breast Cancer Tissues

Objective: This study investigated the incidence and clinical significance of homeodomain-interacting protein kinase 1 expression in breast cancer patients. Methods: We investigated immunohistochemical homeodomain-interacting protein kinase 1 expression from tissue microarrays of 1032 patients. The association of homeodomain-interacting protein kinase 1 expression pattern, clinicopathologic factors and survival outcome was evaluated. Tumors with ≥10% stained cells were considered positive for homeodomain-interacting protein kinase 1. Results: Non-cancerous breast tissue, pTis and pT1mic lesions did not show homeodomain-interacting protein kinase 1 expression at any sites. Of the 859 invasive tumors, 124 (14.4%) showed homeodomain-interacting protein kinase 1 expression with three different expression patterns: cytoplasmic (2.4%), nuclear (6.3%), and both cytoplasmic and nuclear (5.7%). Cytoplasmic homeodomain-interacting protein kinase 1-positive tumors showed distinctive features such as fewer nodal metastases, but were frequently Grade III, estrogen receptor-negative, progesterone receptor-negative, HER2-positive, highly proliferative and molecular apocrine tumors. No significant difference in clinicopathologic features was identified between negative and nuclear homeodomain-interacting protein kinase 1-positive tumors. Both cytoplasmic and nuclear HIPK1-positive tumors represent frequent small size, node negativity and moderately differentiated features. Survival was not significantly different by homeodomain-interacting protein kinase 1 expression patterns. Conclusions: Homeodomain-interacting protein kinase 1 expression was identified only in invasive breast cancer cells with three different patterns: cytoplasmic, nuclear, and both cytoplasmic and nuclear. Although the mechanism is not certain, the subcellular localization of HIPK1 expression is associated with tumor histopathologic characteristics and different functions.