Abstract PR12: Nuclear HSET, a predictor for metastasis, disease relapse, and poor survival, is a racial disparity biomarker in triple-negative breast cancer patients

Introduction: Human spleen, embryo, and testes protein (HSET, also known as KifC1) is a minus end-directed kinesin that has recently been implicated in carcinogenesis. HSET overexpression predicts lung cancer metastasis to the brain, and HSET is upregulated in triple-negative (TN) breast cancer that most commonly occurs in African American (AA) patients. While mounting evidence links HSET to tumorigenesis, especially in the breast, HSET is yet to be evaluated as a clinical biomarker in breast cancer. Here, we investigated the association of HSET with demographic and clinicopathological factors and disease progression in breast tumors among ethnically-distinct populations. Methods: HSET expression was analyzed by immunohistochemistry of formalin-fixed, paraffin-embedded breast carcinoma core biopsies from 149 African American (AA) and 44 Caucasian (CA) totaling 193 patients. Immunostaining was assessed semi-quantitatively for the nucleus and cytoplasm separately. Weighted indices were correlated with tumor and patient characteristics (including ethnicity) along with clinical outcomes. Results: We found that nuclear HSET expression was highly associated with race, with AA women being thrice as likely to present with nuclear localization compared to CA regardless of TN status. Nuclear HSET expression was also significantly associated with the proliferation marker Ki67 and clinicopathological factors like tumor grade, stage, and size; Nottingham prognostic index (NPI); and TN status. High HSET expression was exclusively associated with poorer outcomes in AA patients and not in CA patients. Within the AA population subset, patients with the highest tertile of HSET expression demonstrated the poorest overall survival (HR = 4.1, p = 0.007), progression-free survival (HR = 3.0, p = 0.014), and metastasis-free survival (HR = 3.5, p = 0.01). These associations were also significant using HSET as a continuous variable in multivariate analysis when potentially confounding factors like age, TN status, and tumor stage were matched. Interestingly, overall, progression-free, and metastasis-free survival were significantly associated with nuclear but not cytoplasmic HSET. Conclusions: Expression of nuclear HSET is a valuable prognostic biomarker in AA but not in CA breast cancer patients, underscoring its role in the aggressiveness of this disease in the AA population. HSET overexpression appears to be correlated with poorer prognosis in AA breast cancer patients even after adjusting for age, TN status and other tumor characteristics. In summary, our study is the first to identify and report HSET as a novel clinical biomarker of worse prognosis in AA women with breast cancer. This abstract is also presented as Poster C17. Citation Format: Angela Ogden, Gabriela Oprea-Ilies, Padmashree CG Rida, Dana Nickleach, Yuan Liu, Guilherme Cantuaria, Ritu Aneja. Nuclear HSET, a predictor for metastasis, disease relapse, and poor survival, is a racial disparity biomarker in triple-negative breast cancer patients. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PR12. doi:10.1158/1538-7755.DISP13-PR12