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Published on: April 18, 2025
The Status of CTLA-4 in Colorectal Carcinomas; Relationship with Prognostic Parameters, Her-2 and MMR Proteins
Ismail Saygin1, Zeynep Turkmen Usta1, Ahmet Akbas2
1Department of Pathology, Karadeniz Technical University, Faculty of Medicine, TRABZON, TÜRKİYE.
Objective:
Colorectal cancer (CRC) is the third most common type of cancer worldwide and the fourth most common cause of cancer-related deaths. Innovative approaches like immunotherapy are necessary for treatment-resistant patients with a poor prognosis. This study aimed to investigate the status of CTLA-4, one of the immune checkpoint molecules, in CRCs.
Material And Methods:
A total of 183 resected CRCs were analyzed retrospectively. Immunohistochemical staining was conducted using an anti-CTLA-4 antibody. The relationship between CTLA-4 and prognostic parameters, such as HER2 and microsatellite instability (MSI), was investigated.
Results:
One hundred and four of the cases were male, and 79 were female. One hundred fifty-nine of the cases were conventional adenocarcinomas, while 24 were mucinous adenocarcinomas. In 53 of the cases (29%), CTLA-4 showed less than 1% staining in the immune cells, classifying it as negative. In the remaining cases (71%), varying degrees of immune cell staining with CTLA-4 were observed. Conventional adenocarcinomas exhibited a higher expression of CTLA-4 compared to mucinous carcinomas. No statistically significant correlation was found between MSI status and CTLA-4 immune cell staining (p = 0.572). CTLA-4 positivity decreased significantly as tumor diameter decreased (p = 0.029). There was no correlation between the CTLA-4 immunostaining and median survival time.
Conclusion:
CTLA-4 expression was detected in 71% of CRCs. CTLA-4 positivity significantly decreased as tumor diameter decreased. There was no significant association between CTLA-4 expression and MSI or other prognostic parameters. Additionally, no significant correlation was found between CTLA-4 expression and median survival time. Nevertheless, the presence of CTLA-4 expression in the majority of CRCs is promising for anti-CTLA-4 therapy.
Insights
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) was detected in 71% of colorectal cancers (CRCs). CTLA-4 positivity decreased with smaller tumor size, showing potential for anti-CTLA-4 therapy in CRC treatment.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally.
- Immunotherapy offers novel treatment avenues for patients with advanced or resistant CRC.
- Immune checkpoint molecules, such as CTLA-4, are critical targets in cancer immunotherapy.
Purpose of the Study:
- To investigate the expression status of CTLA-4 in resected colorectal cancer (CRC) specimens.
- To explore the correlation between CTLA-4 expression and clinicopathological prognostic parameters in CRC.
- To assess the potential of CTLA-4 as a therapeutic target in CRC.
Main Methods:
- Retrospective analysis of 183 surgically resected CRC cases.
- Immunohistochemical staining using an anti-CTLA-4 antibody to assess immune cell expression.
- Statistical analysis to evaluate relationships between CTLA-4 expression, tumor characteristics, microsatellite instability (MSI), and survival.
Main Results:
- CTLA-4 expression was observed in immune cells in 71% of CRC cases.
- Higher CTLA-4 expression was noted in conventional adenocarcinomas compared to mucinous adenocarcinomas.
- CTLA-4 positivity significantly decreased with decreasing tumor diameter (p=0.029), but no correlation with MSI or median survival was found.
Conclusions:
- CTLA-4 is expressed in a majority of colorectal cancers, indicating its potential role in the tumor microenvironment.
- While not correlated with MSI or survival, CTLA-4 expression's inverse relationship with tumor size warrants further investigation.
- The prevalent expression of CTLA-4 suggests that anti-CTLA-4 therapies could be a promising strategy for a significant subset of CRC patients.