Abstract B05: Centrosomal profiles of pancreatic adenocarcinoma from African American and European American patients: A comparative analysis

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2015-10, Vol.24 (10_Supplement), p.B05-B05
• Main Authors: Mittal, Karuna, Pannu, Vaishali, Rida, Padmashree C.G., Klimov, Sergy, Dharma, Sanam Sahjram, Ketema, Helina w., Reid, Michelle Dian, Aneja, Ritu
• Format: Article
• Language: English
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1538-7755.DISP14-B05

Background: Mortality from pancreatic cancer is higher in African-Americans (AA) compared to European Americans (EA). Although recent studies have focused on identification of gene expression signatures in whole tumors with variable metastatic potential, a disparity at the organelle-level between tumors of differing aggressiveness and metastatic potential has remained unexplored. Given the long-standing association between centrosome amplification (CA) and aggressiveness, we hypothesized that AA have a higher incidence and severity of CA in pancreatic adenocarcinomas as compared to EA. To test this hypothesis, we have developed an innovative method to quantitate the degree of CA (both numeral and structural) within tumor samples and defined a measurable index called the Centrosome Amplification Score (CAS). Experimental Design: Tissue specimens from 39 EA and 29 AA pancreatic adenocarcinomas were immunostained for centrosomes (gamma-tubulin) and nuclei (Hoechst). Immunofluorescence confocal imaging was then used to stack/take optical sections of tumor tissue and capture all centrosomes and nuclei within 10 regions of interest (ROIs) per sample. Centrosomes were categorized as (i) individually-distinguishable centrosomes (iCTRs) or (ii) as mega centrosomes (mCTRs) comprised of several tightly clustered centrosomes whose precise number could not be determined. For each ROI, the number of nuclei as well as the numbers and volumes of iCTRs and mCTRs were determined. The cumulative CAS was obtained for each ROI as CAS total = CASi + CASm (CASi - CAS for iCTRs and CASm - for mCTRs). Results: AA tumors (n=22) exhibit higher mean CASi (16.75 vs 13.6) and CASTotal (26.09 vs 22.48) than grade-matched EA (n=26) suggesting racial disparity at the organellar level (p