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

Abstract

There exist relatively sparse and conflicting data on high-level microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) in cutaneous malignancies. We aimed to determine the expression profiles of MMR proteins (MSH2, MSH6, MLH1, and PMS2) in different progression stages of cutaneous squamous cell carcinoma (cSCC, 102 patients in total) by immunohistochemistry, and search for MSI-H in patients with low-level MMR or dMMR using multiplex-PCR. Low-level MMR protein expression was observed in five patients: One patient with primary cSCC < 2 mm thickness and low-level MLH1, three patients with primary cSCC > 6 mm (including one with low-level MSH2, as well as MSH6 expression, and two with low-level PMS2), and one patient with a cSCC metastasis showing low-level MSH2 as well as MSH6. Intergroup protein expression analysis revealed that MLH1 and MSH2 expression in actinic keratosis was significantly decreased when compared to Bowen's disease, cSCC < 2 mm, cSCC > 6 mm, and cSCC metastasis. In cases with low-level MMR, we performed MSI-H tests revealing three cases with MSI-H and one with low-level MSI-L. We found low-level MMR expression in a small subset of patients with invasive or metastatic cSCC. Hence, loss of MMR expression may be associated with tumour progression in a small subgroup of patients with non-melanoma skin cancer.

• Authors: Thilo Gambichler, Nomun Ganjuur, Andrea Tannapfel, Markus Vogt, Lisa Scholl, Nessr Abu Rached, Stefanie Bruckmüller, Marina Skrygan, Jürgen C Becker, Heiko U Käfferlein, Thomas Brüning, Kerstin Lang
• Journal: Current oncology (Toronto, Ont.) (Curr Oncol) Vol. 28 Issue 5 Pg. 3316-3322 (08 27 2021) ISSN: 1718-7729 [Electronic] Switzerland
• PMID: 34590599 (Publication Type: Journal Article)

Chemical References

• DNA-Binding Proteins
• Mismatch Repair Endonuclease PMS2
• MutL Protein Homolog 1
• MutS Homolog 2 Protein

Topics

• Carcinoma, Squamous Cell (genetics)
• DNA Mismatch Repair (genetics)
• DNA-Binding Proteins (genetics, metabolism)
• Humans
• Microsatellite Instability
• Mismatch Repair Endonuclease PMS2 (genetics, metabolism)
• MutL Protein Homolog 1 (genetics, metabolism)
• MutS Homolog 2 Protein (genetics, metabolism)
• Skin Neoplasms (genetics)