Exosomal markers (CD63 and CD9) expression and their prognostic significance using immunohistochemistry in patients with pancreatic ductal adenocarcinoma

Moh’d Khushman, Girijesh Kumar Patel, Javier Ariel Laurini, Arun Bhardwaj, Kelly Roveda, Robert Donnell, Kelley Sherling, Brittany Case, Arthur E. Frankel, Sachin Pai, William Taylor, Marcus Chuan Beng Tan, Meir Mizrahi, Cindy Nelson, Mary Wyatt, Mary Patton, Steven McClellan, Seema Singh, Bin Wang, Ajay P. Singh

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)695-702
Number of pages8
JournalJournal of Gastrointestinal Oncology
Volume10
Issue number4
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

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Adenocarcinoma
Disease-Free Survival
Immunohistochemistry
Survival
Staining and Labeling
Neoplasms
African Americans
Pancreas
Exosomes
Proportional Hazards Models
Neoplasm Metastasis

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

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Exosomal markers (CD63 and CD9) expression and their prognostic significance using immunohistochemistry in patients with pancreatic ductal adenocarcinoma. / Khushman, Moh’d; Patel, Girijesh Kumar; Laurini, Javier Ariel; Bhardwaj, Arun; Roveda, Kelly; Donnell, Robert; Sherling, Kelley; Case, Brittany; Frankel, Arthur E.; Pai, Sachin; Taylor, William; Tan, Marcus Chuan Beng; Mizrahi, Meir; Nelson, Cindy; Wyatt, Mary; Patton, Mary; McClellan, Steven; Singh, Seema; Wang, Bin; Singh, Ajay P.

In: Journal of Gastrointestinal Oncology, Vol. 10, No. 4, 01.01.2019, p. 695-702.

Research output: Contribution to journalArticle

Khushman, M, Patel, GK, Laurini, JA, Bhardwaj, A, Roveda, K, Donnell, R, Sherling, K, Case, B, Frankel, AE, Pai, S, Taylor, W, Tan, MCB, Mizrahi, M, Nelson, C, Wyatt, M, Patton, M, McClellan, S, Singh, S, Wang, B & Singh, AP 2019, 'Exosomal markers (CD63 and CD9) expression and their prognostic significance using immunohistochemistry in patients with pancreatic ductal adenocarcinoma', Journal of Gastrointestinal Oncology, vol. 10, no. 4, pp. 695-702. https://doi.org/10.21037/jgo.2018.07.02
Khushman, Moh’d ; Patel, Girijesh Kumar ; Laurini, Javier Ariel ; Bhardwaj, Arun ; Roveda, Kelly ; Donnell, Robert ; Sherling, Kelley ; Case, Brittany ; Frankel, Arthur E. ; Pai, Sachin ; Taylor, William ; Tan, Marcus Chuan Beng ; Mizrahi, Meir ; Nelson, Cindy ; Wyatt, Mary ; Patton, Mary ; McClellan, Steven ; Singh, Seema ; Wang, Bin ; Singh, Ajay P. / Exosomal markers (CD63 and CD9) expression and their prognostic significance using immunohistochemistry in patients with pancreatic ductal adenocarcinoma. In: Journal of Gastrointestinal Oncology. 2019 ; Vol. 10, No. 4. pp. 695-702.
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author = "Moh’d Khushman and Patel, {Girijesh Kumar} and Laurini, {Javier Ariel} and Arun Bhardwaj and Kelly Roveda and Robert Donnell and Kelley Sherling and Brittany Case and Frankel, {Arthur E.} and Sachin Pai and William Taylor and Tan, {Marcus Chuan Beng} and Meir Mizrahi and Cindy Nelson and Mary Wyatt and Mary Patton and Steven McClellan and Seema Singh and Bin Wang and Singh, {Ajay P.}",
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T1 - Exosomal markers (CD63 and CD9) expression and their prognostic significance using immunohistochemistry in patients with pancreatic ductal adenocarcinoma

AU - Khushman, Moh’d

AU - Patel, Girijesh Kumar

AU - Laurini, Javier Ariel

AU - Bhardwaj, Arun

AU - Roveda, Kelly

AU - Donnell, Robert

AU - Sherling, Kelley

AU - Case, Brittany

AU - Frankel, Arthur E.

AU - Pai, Sachin

AU - Taylor, William

AU - Tan, Marcus Chuan Beng

AU - Mizrahi, Meir

AU - Nelson, Cindy

AU - Wyatt, Mary

AU - Patton, Mary

AU - McClellan, Steven

AU - Singh, Seema

AU - Wang, Bin

AU - Singh, Ajay P.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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