Abstract B05: Centrosomal profiles of pancreatic adenocarcinoma from African American and European American patients: A comparative analysis
Authors: Mittal Karuna , Pannu Vaishali , Rida Padmashree C.G. , Klimov Sergy , Dharma Sanam Sahjram , Ketema Helina w. , Reid Michelle Dian , Aneja Ritu 
Published: October 2015

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&lt;0.05). We also found that Grade 2 tumors exhibited higher mean CASTotal (18.9 vs 11.1) compared to Grade 3 regardless of race (p&lt;0.05).

Conclusion: Our results suggest that an aggressive disease course in AA can be attributed to higher degree and severity of CA (in particular numerical amplification) as compared to EA patients and may render AA more sensitive to centrosome targeting/declustering drugs. Our data compellingly suggest the potential usefulness of CAS in enabling patient stratification to channel patients into optimal treatment regimens with an overall goal of eliminating ethnic disparities in pancreatic cancer outcomes.

Citation Format: Karuna Mittal, Vaishali Pannu, Padmashree C.G. Rida, Sergy Klimov, Sanam Sahjram Dharma, Helina w. Ketema, Michelle Dian Reid, Ritu Aneja. Centrosomal profiles of pancreatic adenocarcinoma from African American and European American patients: A comparative analysis. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B05.