The relationship between metastatic status and exosomal marker (CD63) expression using immunohistochemistry (IHC) in patients with pancreatic ductal adenocarcinoma (PDAC)

Introduction: Exosomes are important mediators of intercellular communication, and play pivotal roles in cancer progression, metastasis and chemoresistance. Tumor-derived exosomes prepare a favorable microenvironment at future metastatic sites and mediate non-random pattern of metastasis. Exosomal membranes are enriched in endosomes-specific tetraspanins (CD63 and CD9). In patients with PDAC, the relationship between CD9 expression and metastatic status was not statistically significant. However, CD63 expression was conserved in all patients without reported prognostic significance. Here, we explored the relationship between CD63 expression using IHC and metastatic status in patients with PDAC of mixed gender and racial background. Methods: Between 2012 and 2016, 49 patients with PDAC treated at Mitchell Cancer Institute had available tissue (pancreatic resected tissue/biopsy [N = 29] or metastatic site biopsy liver, omentum or bone (N = 20)) for CD63 staining using IHC. Two pathologists independently scored the expression of CD63. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean Quick-score (Intensity X Percentage of staining) was calculated. Unpaired t test was used for statistical analysis. Results: Median age was 64 years (range 42-85). 53% are males. 67% white, 27% African Americans (AA) and 6% are other ethnicities. 41% had stage IV disease while 59% had stage I, II and III. Tumor involved the head (51%), body (20%) and tail (29%). The mean CD63 Q score is slightly higher in AA compared to white (157 vs 149, P = 0.76). The mean CD63 Q score is higher in patients with no metastasis compared to patients with metastasis to distant organs (179 Vs 111, P = 0.0026). Conclusion: In our cohort of patients with PDAC, there was no racial difference in CD63 expression between white and AA. The expression of CD63 is higher in patients with no metastasis compared to patients with metastasis to distant organs. To our knowledge, this is the first study to show a correlation between CD63 expression and metastatic status in patients with PDAC using IHC.