PTGER2 overexpression in colorectal cancer is associated with microsatellite instability, independent of CpG island methylator phenotype.
Abstract | BACKGROUND: 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. 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. CONCLUSION: IMPACT: Our data imply potential roles of inflammatory reaction by PTGER2 upregulation in carcinogenic process to MSI-high colorectal cancer.
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Authors | Yoshifumi Baba, Katsuhiko Nosho, Kaori Shima, Wolfram Goessling, Andrew T Chan, Kimmie Ng, Jennifer A Chan, Edward L Giovannucci, Charles S Fuchs, Shuji Ogino |
Journal | 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)
Vol. 19
Issue 3
Pg. 822-31
(Mar 2010)
ISSN: 1538-7755 [Electronic] United States |
PMID | 20200425
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- PTGER2 protein, human
- Receptors, Prostaglandin E
- Receptors, Prostaglandin E, EP2 Subtype
- Tumor Suppressor Protein p53
- beta Catenin
- Cyclooxygenase 2
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Topics |
- Biomarkers, Tumor
(genetics)
- Colorectal Neoplasms
(genetics, metabolism, mortality)
- CpG Islands
(genetics)
- Cyclooxygenase 2
(biosynthesis)
- DNA Methylation
(genetics)
- Female
- Humans
- Immunohistochemistry
- Kaplan-Meier Estimate
- Male
- Microsatellite Instability
- Phenotype
- Prognosis
- Receptors, Prostaglandin E
(biosynthesis, genetics)
- Receptors, Prostaglandin E, EP2 Subtype
- Reverse Transcriptase Polymerase Chain Reaction
- Tumor Suppressor Protein p53
(biosynthesis)
- beta Catenin
(biosynthesis)
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