Mismatch Repair Protein Expression and Microsatellite Instability in Cutaneous Squamous Cell Carcinoma

Area of Science:

• Oncology
• Dermatology
• Molecular Biology

Background:

• Data on high-level microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) in cutaneous malignancies are sparse and conflicting.
• Mismatch repair (MMR) proteins are crucial for DNA repair, and their deficiency is linked to various cancers.

Purpose of the Study:

• To investigate MMR protein expression profiles across different stages of cutaneous squamous cell carcinoma (cSCC).
• To identify the prevalence of MSI-H in patients with low-level MMR or dMMR in cSCC.

Main Methods:

• Immunohistochemistry was used to assess MMR protein (MSH2, MSH6, MLH1, PMS2) expression in 102 cSCC patients.
• Multiplex-PCR was employed to detect MSI-H in patients with identified low-level MMR or dMMR.

Main Results:

• Low-level MMR protein expression was detected in five patients with primary cSCC or metastasis.
• MLH1 and MSH2 expression decreased significantly from actinic keratosis to invasive cSCC and metastasis.
• MSI-H testing revealed three cases of MSI-H and one of low-level MSI-L among patients with low-level MMR.

Conclusions:

• Low-level MMR expression is found in a small subset of invasive or metastatic cSCC.
• Loss of MMR expression may be associated with tumor progression in a specific subgroup of non-melanoma skin cancer patients.