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Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability
R Gafà1, I Maestri, M Matteuzzi
1Department of Experimental and Diagnostic Medicine, Section of Anatomic Pathology, University of Ferrara, Ferrara, Italy.
Cancer
|November 7, 2000
Summary
High-frequency microsatellite instability (MSI-H) in colorectal cancer indicates distinct tumor features and a better prognosis. MSI status is crucial for characterizing these tumors and predicting patient outcomes.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Microsatellite instability (MSI) is present in approximately 15% of sporadic colorectal cancers.
- High-frequency MSI (MSI-H) tumors are thought to have different characteristics and a less aggressive behavior compared to microsatellite-stable (MSS) and low-frequency MSI (MSI-L) tumors.
- This study aimed to precisely define the clinicopathologic and biologic features of MSI-H sporadic colorectal carcinomas.
Purpose of the Study:
- To characterize the distinct clinicopathologic and biologic features of MSI-H sporadic colorectal carcinomas.
- To investigate the relationship between MSI status and tumor characteristics, including p53 expression and DNA ploidy.
- To evaluate the prognostic significance of MSI status in colorectal cancer.
Main Methods:
- Evaluated MSI status in 216 colorectal adenocarcinomas using polymerase chain reaction (PCR) and 6 microsatellite markers.
- Classified tumors as MSI-H (instability in ≥2 markers), MSI-L (instability in 1 marker), or MSS (no instability).
- Assessed p53, hMLH1, hMSH2 expression via immunohistochemistry, DNA ploidy by flow cytometry, and analyzed prognostic significance using survival analyses.
Main Results:
- MSI-H tumors showed distinct features: proximal location, larger size, mucinous/medullary histotype, poor differentiation, expanding growth, prominent lymphoid reaction, and less extramural vein invasion.
- MSI-H tumors were predominantly DNA diploid (82.5%) and p53 negative (77.3%).
- MSI-L/MSS tumors frequently exhibited DNA aneuploidy (82.3%) and p53 overexpression (54.1%). Loss of hMLH1/hMSH2 expression was high in MSI-H tumors (86%). Patients with MSI-H tumors had a better outcome (P=0.0017), and MSI status was an independent prognostic indicator.
Conclusions:
- Assessment of MSI status is essential for the genetic characterization of colorectal carcinomas.
- MSI status identifies a subset of colorectal tumors with unique clinical, pathologic, and biologic features.
- MSI status is a significant independent prognostic indicator for disease-specific survival in colorectal cancer.