Background: Mesothelin is a cell surface glycoprotein overexpressed in 28%-58% of colorectal cancer (CRC). We hypothesized that CRC mesothelin expression contributes to peritoneal spread and that it is selectively overexpressed in those with peritoneal metastasis versus distant metastasis.
Methods: This case-controlled study involved mesothelin immunohistochemistry staining of tumor specimens from patients with metastatic CRC/appendiceal cancers between 2017 and 2019. Staining reactivity was graded from trace to 4+ (low ≤1+; high >1+). Staining patterns were characterized on global (focal/patchy/diffuse) and cellular (apical/cytoplasmic) levels. Immunostaining of normal mesothelial cells served as internal control.
Results: Thirty-one patients were identified: 11 peritoneal (study) and 20 distant metastasis (control). The control group did not include appendiceal cancers. The study group had greater proportion of high staining reactivity (55% vs. 5%; odds ratio [OR] = 20.4, 95% confidence interval [CI] 1.96-211.8). The study group had more diffuse (36% vs. 0%; OR = 22.2, 95% CI 1.1-465.3) and cytoplasmic staining patterns (73% vs. 28%; OR = 6.9, 95% CI 1.3-37.2).
Conclusion: Mesothelin expression is higher in CRC/appendiceal cancers with peritoneal metastasis than those with distant metastasis. Immunohistochemistry staining patterns suggestive of propensity towards peritoneal metastasis include diffuse and cytoplasmic staining. Mesothelin may be a potential target for novel treatments of CRC/appendiceal carcinoma with peritoneal involvement.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/jso.26610 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Excess shed mesothelin disrupts pancreatic cancer cell clustering to impair peritoneal colonization.
FASEB J
December 2024
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Peritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Peritoneal colonization is impaired in PDAC cells with knockout (KO) of the cancer surface antigen mesothelin (MSLN) or by introducing Y318A mutation in MSLN to prevent binding to mucin-16 (MUC-16). MSLN has a membrane-bound form but is also shed to release soluble MSLN (sMSLN).
View Article and Find Full Text PDFMesothelin expression prediction in pancreatic cancer based on multimodal stochastic configuration networks.
Med Biol Eng Comput
December 2024
Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518071, China.
Predicting tumor biomarkers with high precision is essential for improving the diagnostic accuracy and developing more effective treatment strategies. This paper proposes a machine learning model that utilizes CT images and biopsy whole slide images (WSI) to classify mesothelin expression levels in pancreatic cancer. By combining multimodal learning and stochastic configuration networks, a radiopathomics mesothelin-prediction system named RPMSNet is developed.
View Article and Find Full Text PDFEndothelial Angpt2 Promotes Adipocyte Progenitor Cells Maturation to Increase Visceral Adipose Tissue Accumulation.
Diabetes Metab Res Rev
January 2025
Department of General Surgery, The Third Xiangya Hospital, Central South University, Changsha, China.
Aims: Visceral adipose tissue (VAT) accumulation is essential for the occurrence and development of obesity and related metabolic diseases. Currently, the specific mechanism of VAT accumulation is still unclear.
Materials And Methods: We searched the Gene Expression Omnibus database to obtain single-cell RNA sequencing (scRNAseq) data for VAT in patients with a normal body mass index (BMI), obesity, or morbid obesity.
Repurposing anti-mesothelin CAR-NK immunotherapy against colorectal cancer.
J Transl Med
December 2024
Candiolo Cancer Institute, FPO-IRCCS, Candiolo, TO, Italy.
Background: Colorectal cancer (CRC) is the third most common cancer worldwide, with highly variable prognosis and response to treatment. A large subset of patients does not respond to standard treatments or develops resistance. As an alternative, adoptive immunotherapy based on chimeric antigen receptor (CAR)-transduced immune cells has been proposed, however with significant adverse events.
View Article and Find Full Text PDFCombinational CAR T-cell therapy for solid tumors: Requisites, rationales, and trials.
Pharmacol Ther
November 2024
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Chimeric antigen receptor (CAR) T-cell therapy has achieved potent antitumor efficacy in hematological malignancies; however, because of limitations in CAR T-cell recruitment, infiltration, activation, and functional persistence in the tumor, its efficacy in solid tumors has been suboptimal. To overcome these challenges, combinational strategies that include chemotherapy, radiation therapy, or immune checkpoint inhibitor agent therapy with CAR T-cell therapy are being investigated. The established functional characteristics of the abovementioned therapies provide a rationale for the use of a combinational approach with CAR T cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!