High-level microsatellite instability in appendiceal carcinomas.

Area of Science:

• Oncology
• Gastroenterology
• Molecular Biology

Background:

• High-level microsatellite instability (MSI-high) is a hallmark of approximately 15% of colorectal adenocarcinomas (CRCs), often linked to MLH1 promoter methylation.
• Familial cases, such as Lynch syndrome, account for a small fraction of CRCs.
• MSI-high is notably rare in appendiceal adenocarcinomas, with limited prior reports.

Observation:

• This study analyzed 108 appendiceal carcinomas for MSI status using immunohistochemistry and polymerase chain reaction.
• Three cases (2.8%) were identified as MSI-high, and one case was MSI-low.
• The MSI-high cases exhibited varied loss of DNA mismatch-repair protein expression (MLH1/PMS2 or MSH2/MSH6) and lacked MLH1 promoter methylation or BRAF mutations.

Findings:

• The prevalence of MSI-high in appendiceal carcinomas was found to be 2.8% (3 out of 108).
• MSI-high rates were 3.1% in invasive carcinomas not arising from goblet cell carcinoid tumors, and 0% in those arising from goblet cell carcinoid tumors.
• The molecular mechanisms for MSI-high in appendiceal cancer appear distinct from the common MLH1 promoter methylation seen in colorectal cancer.

Implications:

• The low frequency of MSI-high in appendiceal cancer suggests it is less common than in the right colon.
• The findings indicate that MLH1 promoter hypermethylation is unlikely to be the primary driver of MSI-high in appendiceal adenocarcinomas.
• Further research is needed to elucidate the specific molecular pathways driving MSI-high appendiceal cancers.