Back to Search
Start Over
PTGER2 overexpression in colorectal cancer is associated with microsatellite instability, independent of CpG island methylator phenotype.
- Source :
-
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2010 Mar; Vol. 19 (3), pp. 822-31. Date of Electronic Publication: 2010 Mar 03. - Publication Year :
- 2010
-
Abstract
- Background: Prostaglandin-endoperoxide synthase 2 (PTGS2, the HUGO Gene Nomenclature Committee-approved official symbol for cycloxygenase-2, COX-2) and its enzymatic product prostaglandin E2 have critical roles in inflammation and carcinogenesis through the G protein-coupled receptor PTGER2 (EP2). The PTGS2 (COX-2) pathway is a promising target for cancer therapy and chemoprevention. PTGS2 (COX-2) expression in colon cancer has been inversely associated with survival as well as tumoral microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). However, the prognostic significance of PTGER2 expression or its relationship with MSI, CIMP, LINE-1 hypomethylation, or PTGS2 (COX-2) remains uncertain.<br />Methods: Using the database of 516 colorectal cancers in two prospective cohort studies with clinical outcome data, we detected PTGER2 overexpression in 169 (33%) tumors by immunohistochemistry. We analyzed MSI using 10 microsatellite markers; CIMP by MethyLight (real-time methylation-specific PCR) on an eight-marker panel [CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1]; BRAF, KRAS, PIK3CA, and methylation in LINE-1 by Pyrosequencing; and CTNNB1 (beta-catenin) and TP53 (p53) by immunohistochemistry.<br />Results: PTGER2 overexpression was positively associated with the mucinous component (P = 0.0016), signet ring cells (P = 0.0024), CIMP-high (P = 0.0023), and MSI-high (P < 0.0001). In multivariate analysis, the significant relationship between PTGER2 and MSI-high persisted (adjusted odds ratio, 2.82; 95% confidence interval, 1.69-4.72; P < 0.0001). PTGER2 was not significantly associated with PTGS2 (COX-2), TP53, or CTNNB1 expression, patient survival, or prognosis.<br />Conclusion: PTGER2 overexpression is associated with MSI-high in colorectal cancer.<br />Impact: Our data imply potential roles of inflammatory reaction by PTGER2 upregulation in carcinogenic process to MSI-high colorectal cancer.
- Subjects :
- Biomarkers, Tumor genetics
Colorectal Neoplasms metabolism
Colorectal Neoplasms mortality
Cyclooxygenase 2 biosynthesis
Female
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Phenotype
Prognosis
Receptors, Prostaglandin E genetics
Receptors, Prostaglandin E, EP2 Subtype
Reverse Transcriptase Polymerase Chain Reaction
Tumor Suppressor Protein p53 biosynthesis
beta Catenin biosynthesis
Colorectal Neoplasms genetics
CpG Islands genetics
DNA Methylation genetics
Microsatellite Instability
Receptors, Prostaglandin E biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7755
- Volume :
- 19
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 20200425
- Full Text :
- https://doi.org/10.1158/1055-9965.EPI-09-1154