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Role of the mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT pathways downstream molecules, phosphorylated extracellular signal-regulated kinase, and phosphorylated AKT in colorectal cancer-a tissue microarray-based approach
- Source :
- Human pathology. 37(8)
- Publication Year :
- 2006
-
Abstract
- Tumor budding is defined as dedifferentiated cancer cells at the invasive margin of colorectal cancer (CRC) and correlates with a worse prognosis. The invasive margin and tumor budding are normally not present in a superficial diagnostic biopsy specimen. The aim of this study was to investigate the expression/overexpression of 2 downstream molecules of the mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT pathways, phosphorylated AKT (pAKT) and phosphorylated extracellular signal-regulated kinase (pERK), in areas of CRC away from the invasive margin and determining if these variables were predictive of tumor budding or prognosis. A series of 1420 unselected, nonconsecutive CRC resections were subdivided into 3 groups: (1) DNA mismatch repair (MMR) proficient, (2) MLH1-negative, and (3) presumed HNPCC. Immunohistochemical analysis of pAKT and pERK expression (0% versus > 0%) and overexpression (increasing percentage of positivity) was performed using the tissue microarray technique. The results were correlated with clinicopathologic parameters. Fifty-seven samples of normal colon mucosa were included as a control group. Nuclear pERK expression (P = .008) was associated with presence of tumor budding in the MMR-proficient, but not in the MLH1-negative and presumed-HNPCC groups. In contrast, cytoplasmic pAKT overexpression was associated with early T stage (P = .04), early N stage (P = .02), and absence of tumor budding (P = .03) only in the MLH1-negative group. There was no association between pERK or pAKT and clinicopathologic parameters in the HNPCC group. Dysregulation of the mitogen-activated protein kinase pathway is likely to be implicated in the mechanism of tumor budding only in MMR-proficient CRC, whereas the phosphoinositide 3-kinase/AKT pathway is associated with early stage in MLH1-negative CRC.
- Subjects :
- MAPK/ERK pathway
Male
Pathology
medicine.medical_specialty
Colon
Biology
Adenocarcinoma
Pathology and Forensic Medicine
Immunoenzyme Techniques
Phosphatidylinositol 3-Kinases
Tumor budding
medicine
Biomarkers, Tumor
Humans
Phosphorylation
Protein kinase A
Extracellular Signal-Regulated MAP Kinases
Fluorescent Antibody Technique, Indirect
Protein kinase B
PI3K/AKT/mTOR pathway
Aged
Cell Nucleus
Tissue microarray
Kinase
Middle Aged
digestive system diseases
Tissue Array Analysis
Cancer research
Female
Signal transduction
Mitogen-Activated Protein Kinases
Colorectal Neoplasms
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 00468177
- Volume :
- 37
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Human pathology
- Accession number :
- edsair.doi.dedup.....a1409f98d8586deb1c50f209808b3ea9