HSET Expression in Triple Negative and Non-Triple Negative Breast Cancers
Gabriela M Oprea-Ilies, Vaishali Pannu, Yuan Liu, Dana Nickleach, Stefan E Pambuccian, Ritu Aneja. Emory University, Atlanta, GA; Georgia State University, Atlanta, GA; Winship Cancer Institute, Atlanta, GA; Loyola University Chicago, Maywood, IL
Background: Chromosomal instability arising from centrosome amplification and mitotic aberrations has long been associated with tumorigenesis. Although amplified centrosomes would be expected to compromise cell viability by compelling cells to form multipolar spindles resulting in death-inducing aneuploidy, cancer cells turn things in their favor by employing clever mechanisms to suppress multipolarity by clustering their supernumerary centrosomes. As a result, cancer cells, with the aid of clustering mechanisms, maintain bipolar spindle phenotypes that are accompanied by low grade aneuploidy, an edge to their survival. HSET is a kinesin-like minus-end directed motor and centrosome clustering molecule/factor that plays an important role in key cellular functions, including mitosis. The aim of the study was to assess the HSET frequency in TNT breast cancers (BC) as compared with BC expressing ER/PR and/or HER (non-TNT).
Design: BC diagnosed during a 7-year period were reviewed. The BC markers ER, PR, and Her-2 scored by the new CAP standards were used to classify the tumors into TNT and non-TNT. Tissue microarrays were stained with an anti-Kinesin-related protein HSET monoclonal antibody (a gift from Claire Walczak, Indiana University). HSET expression was evaluated separately in nuclei and cytoplasm and was semiquantitavely scored as positive on a scale from 1-3. Tumors with more than 1+ staining in >10% of nuclei and more than 1+ and cytoplasmic staining in >50% of tumor cells were considered positive.
Results: Of the 193 BC from 143 African American (AA) and 50 non-African American (non-AA) women aged 24-90, 120 were TNT and 73 were non-TNT. HSET showed cytoplasmic positivity in 65% TNT vs 27% non-TNT, and in 92% African-American (AA) vs 8% non-AA patients. HSET showed nuclear positivity in 63% TNT vs 31% non-TNT, and in 91% AA vs 9% non-AA patients. All differences were staistically significant (p<0.05). There were no statically differences in age, tumor size and lymph node metastases between tumors that showed nuclear or cytoplasmic positivity for HSET and tumors that did not.
Conclusions: 1. HSET shows statically significantly higher nuclear and cytoplasmic expression in TNT vs non-TNT.
2. HSET is expressed in a significantly higher percentage of AA vs non-AA women.
3. Further studies may be useful to determine if HSET represents a useful therapeutic target.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 15, Tuesday Morning