Moh'd Khushman1, Girijesh Kumar Patel2, Javier Ariel Laurini3, Arun Bhardwaj2, Kelly Roveda4, Robert Donnell5, Kelley Sherling5, Brittany Case6, Arthur E Frankel1, Sachin Pai1, William Taylor1, Marcus Chuan Beng Tan7, Meir Mizrahi8, Cindy Nelson1, Mary Wyatt1, Mary Patton2, Steven McClellan2, Seema Singh2, Bin Wang9, Ajay P Singh2. 1. Department of Medical Oncology, The University of South Alabama, Mitchell Cancer Institute, Mobile, AL, USA. 2. Department of Oncologic Sciences, The University of South Alabama, Mitchell Cancer Institute, Mobile, AL, USA. 3. Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA. 4. Department of Pathology, The University of South Alabama, Mobile, AL, USA. 5. Department of Pathology, Mobile Infirmary Health System, Mobile, AL, USA. 6. Department of Internal Medicine, The University of South Alabama, Mobile, AL, USA. 7. Department of Surgical Oncology, Vanderbilt University, Nashville, TN, USA. 8. Department of Gastroenterology, The University of South Alabama, Mobile, AL, USA. 9. Department of Mathematics and Statistics, The University of South Alabama, Mobile, AL, USA.
Abstract
BACKGROUND: Exosomes are important mediators of intercellular communications and play pivotal roles in cancer progression, metastasis and chemoresistance. CD63 and CD9 are widely accepted exosomal markers. In patients with pancreatic ductal adenocarcinoma (PDAC), positive correlation between CD9 expression and overall survival (OS) was reported. CD63 expression was conserved in all patients with no reported prognostic significance. This study explored the prognostic significance of CD63 and CD9 expression using immunohistochemistry (IHC) in patients with PDAC of mixed racial background. METHODS: Between 2012 and 2016, 49 patients with PDAC had available tissues for CD63 and CD9 staining using IHC. Two pathologists independently scored the CD63 and CD9 expression. Staining intensity was graded from 1-3 and staining percentage was estimated in 10% increments. Mean Quick-score (Q-score) (Intensity X Percentage of staining) was calculated. RESULTS: The mean Q-score for CD63 and CD9 are higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites (185 vs. 102, P=0.0002) and (48 vs. 20, P=0.0418) respectively. We fitted Cox proportion hazard regression models to investigate the impact of the covariates CD63 and CD9 on progression free survival (PFS) and OS. CD63 has significant impact on PFS (P=0.0135) and OS (P=0.003). The higher the CD63 Q-score, the longer the PFS and OS. CD9 doesn't have significant impact on PFS (P=0.5734) or OS (P=0.2682). The mean CD63 and CD9 Q-scores are slightly higher in African American (AA) compared to Caucasians (157 vs. 149, P=0.76) and (45 vs. 29, P=0.43) respectively. CONCLUSIONS: CD63 and CD9 expression is higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites. There is correlation between CD63 expression (but not CD9 in this cohort) and PFS and OS. To our knowledge, this is the first study to show prognostic significance of CD63 expression in patients with PDAC using IHC. A trend of higher expression of CD63 and CD9 among AA compared to Caucasians was also noticed.
BACKGROUND: Exosomes are important mediators of intercellular communications and play pivotal roles in cancer progression, metastasis and chemoresistance. CD63 and CD9 are widely accepted exosomal markers. In patients with pancreatic ductal adenocarcinoma (PDAC), positive correlation between CD9 expression and overall survival (OS) was reported. CD63 expression was conserved in all patients with no reported prognostic significance. This study explored the prognostic significance of CD63 and CD9 expression using immunohistochemistry (IHC) in patients with PDAC of mixed racial background. METHODS: Between 2012 and 2016, 49 patients with PDAC had available tissues for CD63 and CD9 staining using IHC. Two pathologists independently scored the CD63 and CD9 expression. Staining intensity was graded from 1-3 and staining percentage was estimated in 10% increments. Mean Quick-score (Q-score) (Intensity X Percentage of staining) was calculated. RESULTS: The mean Q-score for CD63 and CD9 are higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites (185 vs. 102, P=0.0002) and (48 vs. 20, P=0.0418) respectively. We fitted Cox proportion hazard regression models to investigate the impact of the covariates CD63 and CD9 on progression free survival (PFS) and OS. CD63 has significant impact on PFS (P=0.0135) and OS (P=0.003). The higher the CD63 Q-score, the longer the PFS and OS. CD9 doesn't have significant impact on PFS (P=0.5734) or OS (P=0.2682). The mean CD63 and CD9 Q-scores are slightly higher in African American (AA) compared to Caucasians (157 vs. 149, P=0.76) and (45 vs. 29, P=0.43) respectively. CONCLUSIONS: CD63 and CD9 expression is higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites. There is correlation between CD63 expression (but not CD9 in this cohort) and PFS and OS. To our knowledge, this is the first study to show prognostic significance of CD63 expression in patients with PDAC using IHC. A trend of higher expression of CD63 and CD9 among AA compared to Caucasians was also noticed.
Authors: Timothy J Kinsella; Yuji Seo; Joseph Willis; Thomas A Stellato; Christopher T Siegel; Deborah Harpp; James K Willson; Joseph Gibbons; Juan R Sanabria; Jeffrey M Hardacre; James P Schulak Journal: Am J Clin Oncol Date: 2008-10 Impact factor: 2.339
Authors: Johan Skog; Tom Würdinger; Sjoerd van Rijn; Dimphna H Meijer; Laura Gainche; Miguel Sena-Esteves; William T Curry; Bob S Carter; Anna M Krichevsky; Xandra O Breakefield Journal: Nat Cell Biol Date: 2008-11-16 Impact factor: 28.824