Tissue microarray FISH applied to colorectal carcinomas with various microsatellite status

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Colorectal carcinoma (CRC) exhibits etiological heterogeneity, developing via chromosomal instability or DNA repair defects leading to microsatellite instability (MSI).
• CRC classification includes microsatellite-stable (MSS), highly microsatellite unstable (MSI-H), and low-level microsatellite unstable (MSI-L) subtypes.
• Fluorescence in situ hybridization (FISH) is a nucleic acid detection method utilizing fluorescent probes for specific DNA fragment identification.

Purpose of the Study:

• To evaluate the utility of FISH in analyzing chromosomal copy numbers for specific chromosomes (1, 8, 17, 18) in different molecular subtypes of colorectal carcinoma.
• To determine if chromosomal aberrations detected by FISH can differentiate between microsatellite-stable (MSS) and microsatellite-unstable (MSI-H, MSI-L) colorectal cancers.

Main Methods:

• Analysis of 146 colorectal carcinoma cases using histopathological evaluation and tissue microarrays.
• FISH was performed using probes for chromosomes 1, 8, 17, and 18.
• Microsatellite instability was assessed using PCR on frozen tissue samples.

Main Results:

• Mean signal counts for chromosomes 1 and 17 showed minor variations across MSS, MSI-L, and MSI-H groups, with no statistically significant differences.
• Chromosome 18 consistently showed a mean signal count of 2 across all molecular subtypes.
• Chromosome 8 also exhibited minimal variation in mean signal counts between the different MSI groups.

Conclusions:

• The analyzed chromosomal copy number variations (chromosomes 1, 8, 17, 18) detected by FISH are not sufficient to distinguish between microsatellite-stable and microsatellite-unstable colorectal carcinoma subtypes.
• Further research may be needed to identify other chromosomal targets or methodologies for molecular subtyping of colorectal cancer.