Exosomal markers (CD63 and CD9) expression using immunohistochemistry (IHC) in patients with right-sided and left-sided colon cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15119-e15119
Author(s):  
Pranitha Prodduturvar ◽  
Ben McCormick ◽  
Wadad Mneimneh ◽  
Valeria Dal Zotto ◽  
Leander Grimm ◽  
...  

e15119 Background: Embryologically, the right colon (cecum, ascending colon, hepatic flexure and proximal two-thirds of the transverse colon) is derived from the midgut, whereas the left colon (sigmoid colon, descending colon, splenic flexure and distal third of the transverse colon) is derived from the hindgut. There are clinical, pathological and molecular differences between patients with right-sided colon cancer (RSCC) and left-sided colon cancer (LSCC). Exosomes mediate intercellular communications and interactions and have pivotal roles in cancer behavior. CD63 and CD9 are widely accepted exosomal markers. Here we explored CD63 and CD9 expression using immunohistochemistry (IHC) in patients with RSCC and LSCC. Methods: Between 2015 and 2018, 63 patients underwent colon surgical resection for whom we had available tissues for CD63 and CD9 IHC staining. Two pathologists independently scored CD63 and CD9 expression in the tumor and adjacent normal mucosa (ANM). Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Unpaired t test was used for statistical analysis. Results: Median age was 64 (range 33-78). Females represented 60% of our cohort. Caucasians, African Americans and other Ethnicities represented 55%, 40% and 5% respectively. The sidedness was designated as RSCC in 52% and as LSCC in 48%. The ANM and Tumor CD63 Q scores were 225 vs 191 (p = 0.009) in RSCC and 224 vs 154 (p = 0.0001) in LSCC respectively. The ANM and Tumor CD9 Q scores are 134 vs 152 (p = 0.142) in RSCC and 135 vs 154 (p = 0.137) in LSCC respectively. In patients with RSCC and LSCC, the mean Tumor CD63 Q score is 191 vs 154 (p = 0.024), while the mean ANM CD63 Q score is 225 vs 224 (p = 0.920). The mean Tumor CD9 Q score is 152 and 154 (p = 0.883) and the mean ANM CD9 Q score is 134 vs 135 (p = 0.926). Conclusions: In our cohort of patients with RSCC and LSCC, the exosomal marker CD63 expression is lower in the tumor compared to the ANM. While ANM CD63 expression was similar between RSCC and LSCC, tumor CD63 expression was higher in RSCC compared to LSCC. The exosomal marker CD9 was not found to have significant differential expression between ANM and tumor and between RSCC and LSCC. To our knowledge, this is the first study to explore exosomal markers expression using IHC in patients with RSCC and LSCC.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16096-e16096
Author(s):  
Pranitha Prodduturvar ◽  
Ben McCormick ◽  
Wadad Mneimneh ◽  
Valeria Dal Zotto ◽  
Daisy E Escobar ◽  
...  

e16096 Background: Adenocarcinomas arising from the distal one third of the transverse colon, splenic flexure, descending colon, sigmoid colon and rectum are often grouped together due to their hindgut embryologic origin and referred to as left-sided colorectal cancer (CRC). Rectal cancer represents a subset of CRC that has distinct differences in anatomical location, clinical behavior, prognosis and molecular background. In patients with left sided colon cancer (LSCC), the expression of exosomal marker CD63 was reported to be higher in the adjacent normal mucosa (ANM) compared to the tumor (224 vs 154, p = 0.0001). Here, we explored the pattern of CD63 expression using immunohistochemistry in patients with rectal cancer in comparison with patients with LSCC. Methods: Between 2015 and 2018, 53 patients underwent rectal cancer biopsy/resection and had available tissues for CD63 IHC staining. Two pathologists independently scored CD63 expression in the tumor and ANM. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Paired t test was used for statistical analysis. Results: Median age was 60 (range 34-80). Females represented 26%. Caucasians and African Americans represented 74% and 26%, respectively. In patients with rectal cancer, the mean CD63 expression was higher in ANM compared to their expression in the tumor (147 vs 113, p = 0.0012). Compared to patients with LSCC (N = 30), the mean CD63 expression in patients with rectal cancer was lower in the ANM (224 vs 147, p < 0.0001) and in the tumor (154 vs 113, p = 0.01). Conclusions: In our cohort of patients with rectal cancer, exosomal marker CD63 expression was lower in tumor compared to ANM. This observation was similar to our previously reported findings in patients with LSCC. Compared to patients with LSCC, patients with rectal cancer had lower expression of CD63 in the tumor and ANM. To our knowledge, this is the first study to explore exosomal marker CD63 expression using IHC in patients with rectal cancer.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 182-182
Author(s):  
Ben McCormick ◽  
Pranitha Prodduturvar ◽  
Wadad Mneimneh ◽  
Valeria Dal Zotto ◽  
Leander Grimm ◽  
...  

182 Background: Exosomes play pivotal roles in cancer progression, metastasis and chemoresistance. CD63 and CD9 are widely accepted exosomal markers. Their pattern of expression and prognostic significance in patients with RSCC and LSCC is unknown. This study explored CD63 and CD9 expression and prognostic significance in patients with RSCC and LSCC using immunohistochemistry (IHC). Methods: Between 2015 and 2018, 63 patients underwent surgical resection of colon cancer for whom we had available tissues for CD63 and CD9 IHC staining. Two pathologists independently scored the CD63 and CD9 expression in the tumor and adjacent normal mucosa (ANM). Staining intensity was graded 1-3 and staining percentage was estimated in 10% increments. Mean Quick-score (Q-score) (intensity X percentage of staining) was calculated. Results: RSCC and LSCC represented 52% and 48% of the patients respectively. The ANM and Tumor CD63 Q-scores were 225 vs 191 (p = 0.009) in RSCC and 224 vs 154 (p = 0.0001) in LSCC, respectively. The ANM and Tumor CD9 Q-scores were 134 vs 152 (p = 0.142) in RSCC and 135 vs 154 (p = 0.137) in LSCC, respectively. In patients with RSCC and LSCC, the mean Tumor CD63 Q-score was 191 vs 154 (p = 0.024), while the mean ANM CD63 Q-score was 225 vs 224 (p = 0.920). The mean Tumor CD9 Q-score was 152 and 154 (p = 0.883), and the mean ANM CD9 Q-score was 134 vs 135 (p = 0.926). In our cohort, there was no difference in progression free survival (PFS) between patients with RSCC and LSCC (p = 0.2349). In all patients, there was no difference in PFS in patients with CD63 expression < 100 and ≥100 (p = 0.8284). Among patients with RSCC, there was a significantly lower PFS in patients with CD63 expression < 100 vs. ≥100 (p = 0.0259). However, among patients with LSCC, there was no difference in PFS in patients with CD63 expression < 100 vs. ≥100 (p = 0.3494). Conclusions: To our knowledge, this is the first study to show a difference in exosomal marker (CD63) expression pattern and its prognostic significance in patients with RSCC and LSCC. There was a significant positive correlation between progression free survival in patients with RSCC and higher exosomal expression.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15730-e15730
Author(s):  
Moh'd M. Khushman ◽  
Arun Bhardwaj ◽  
Girijesh K. Patel ◽  
Javier Laurini ◽  
Kelly Roveda ◽  
...  

e15730 Background: Exosomes are important mediators of intercellular communication, and play pivotal roles in cancer progression, metastasis and chemoresistance. Exosomal membranes are enriched in endosomes-specific tetraspanins (CD63 and CD9). In patients with PDAC, positive correlation between CD9 expression and overall survival (OS) was reported. However, CD63 expression was conserved in all patients without reported prognostic significance. Here, we explored the prognostic significance of CD63 expression using IHC 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 49% 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 the pancreatic tissues compared to metastatic sites tissues (185 Vs 102, P = 0.0002). In our cohort, patients with mean CD63 Q score > = 140 had longer median OS compared to patients with mean Q score of < 140 (19 months Vs 3 months, P = 0.0003) and progression free survival (PFS) (12 months vs 1 month, P = 0.0043). Conclusions: 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 the pancreas compared to metastatic sites (liver, omentum and bone). There is positive correlation between CD63 expression 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.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 101-101
Author(s):  
Moh'd M. Khushman ◽  
Pranitha Prodduturvar ◽  
Shalla Akbar ◽  
Wadad Mneimneh ◽  
Valeria Dal Zotto ◽  
...  

101 Background: Exosomes mediate intercellular communications and have pivotal roles in cancer development. CD63 and CD9 are widely accepted exosomal markers. The effect of concurrent chemoradiation on the expression of exosomal markers is unknown. Here we explored the effect of neoadjuvant concurrent chemoradiation (NCCR) on exosomal markers (CD63 and CD9) expression in patients with locally advanced rectal cancer (LARC). Methods: Between 2015 and 2018, 33 patients had LARC treated with NCCR and had pre NCCR biopsy and post NCCR resected rectum examined for exosomal markers expression using immunohistochemistry. Two pathologists independently scored CD63 and CD9 staining in the tumor. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Un-Paired t test was used for statistical analysis. Results: In our cohort, median age was 59 years. Males represented 79% of the patients. Caucasians, African American and other ethnic groups represented 70%, 27% and 3% respectively.The mean tumor CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 106 vs 165 (p = 0.0022). The mean tumor CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 136 vs 215 (p < 0.0001). The exosomal markers expression in the adjacent normal mucosa (ANM) from pre NCCR biopsy and post NCCR resected rectum was only performed in16 out of 33 patients (due to ANM tissue availability). The mean ANM CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 166 vs 183 (p = 0.37). The mean ANM CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 104 vs 145 (p = 0.0897). Conclusions: In patients with LARC, the expression of exosomal markers (CD63 and CD9) increased after treatment with NCCR. Our results show that the expression of CD63 and CD9 is relatively higher in rectal cancer specimens treated with NCCR and thus suggest a possible role of these exosomes in adaptive response to NCCR. Further follow-up and laboratory studies are required to precisely understand the underlying mechanism(s).


2021 ◽  
Vol 9 (11) ◽  
pp. 454-458
Author(s):  
Reem Mohammed Alshiakh ◽  
◽  
Ahmad Omar Alghamdi ◽  
Suhad Ali Aljuhani ◽  
Hadeel Hamid Ahmad ◽  
...  

Malignant neoplasms of the colon and rectum are often missed in patients younger than 45 years, the uncertainty of the diagnosis by the surgical team due to unavailability of clear screening guidelines in this population may be one of the reasons. The objective of this case report is to highlight the occurrence of colon cancer in a patient younger than 45 years to avoid the delay in management and the need for clear screening guidelines. Our patient, a 30 years old lady with an average risk of colon cancer demonstrated clinical symptoms and signs suggestive of partial bowel obstruction. After full radiological and laboratory investigations, she was initially diagnosed with inflammatory vs infectious cause of this obstruction. Colonoscopy showed a mass in the right hepatic flexure and sessile polyp in the transverse colon, Histopathology result showed moderately differentiated colon cancer. The patient was taken to the operation theater, right extended hemicolectomy was done, final histopathology result showed stage IIIc cancer, the patient was sent for oncology. In a conclusion, Colon cancer in patients younger than 45 years old requires a high index of suspicion by the surgeon and the managing team despite the unavailability of clear guidelines for screening at a young age.


2020 ◽  
Vol 34 (12) ◽  
pp. 5640-5641 ◽  
Author(s):  
Masanobu Enomoto ◽  
Kenji Katsumata ◽  
Kenta Kasahara ◽  
Tomoya Tago ◽  
Naoto Okazaki ◽  
...  

Abstract Background Complete mesocolic excision (CME) is known to be effective for colon cancer. However, in right-sided colon cancer, central vascular ligation (CVL) is not easy to perform. In particular, in patients in whom the superior mesenteric vein (SMV) runs on the ventral side of the superior mesenteric artery (SMA) (Type V/A), laparoscopic ligation of the artery at its root is extremely difficult compared with this procedure in patients in whom the SMA runs on the ventral side of the SMV (Type A/V). Methods We started performing laparoscopic CME with true CVL for right-sided colon cancer using the SMA as a landmark in 2015, and by 2019, we had completed it for 60 patients. To start, the mesocolon is opened well to the caudal side of the ileocolic vessels. The mesentery is then fully detached from the retroperitoneal tissue, after which the ileocolic vessels are ligated at their roots. D3 lymph node dissection of the lymph nodes around the SMA and SMV on the resection side is also performed using the SMA as a landmark, and depending on the location of the tumor, the roots of the right and middle colic vessels are ligated and divided. This study was conducted with the approval of the Tokyo Medical University Ethics Committee. All patients provided informed consent. Results The tumor was located in the cecum in 21 cases, the ascending colon in 33, and the transverse colon in 6. The mean operating time was 229 min and the mean volume of hemorrhage was 67 ml. There was one Clavien-Dindo Grade 3 or worse postoperative complication (ileus). There were no surgery-related or in-hospital deaths. Conclusion This procedure can be performed comparatively safely. However, since it requires some skill, we consider that it should only be performed in suitable cases by teams with sufficient experience.


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