Mismatch repair protein loss in cutaneous head and neck squamous cell carcinoma

Abstract

Background The treatment of advanced cutaneous head and neck cutaneous squamous cell carcinomas (HNcSCC) results in significant morbidity. Recently, immune checkpoint inhibitor treatment has been approved for DNA mismatch repair (MMR) deficient patients in a histology‐agnostic manner. This study aims to evaluate the incidence of MMR deficiency in advanced HNcSCC and its association with clinicopathologic factors. Methods The cohort included 176 consecutive HNcSCC cases treated with curative intent. Immunohistochemistry for MMR proteins (hMLH1, hMSH2, hMSH6, and hPMS2) was performed. Clinicopathological and survival data was collected prospectively. Results The incidence of MMR protein deficiency was 9.1%. There was no association between age, incidence of metachronous malignancies, clinicopathological factors, or survival outcomes. Conclusion A higher incidence of MMR deficiency was observed in this cohort of advanced HNcSCC. The lack of association with young age at onset or increased incidence of metachronous malignancies suggests that MMR deficiency is likely to be sporadic in HNcSCC.

Response to ‘Cutaneous squamous cell carcinoma is associated with Lynch syndrome: widening the spectrum of Lynch syndrome‐associated tumours’

“…This is comparable with the frequency of MMR deficiency in LS tumours that are within the accepted LS tumour spectrum, such as colorectal and endometrial cancer, 2 and is much greater than the < 10% frequency of MMR deficiency in unselected cSCC. 6,7 Our findings are also consistent with the IHC results of Ykema et al However, only three of nine of their cSCCs were MSI-H despite 10 of 10 being MMRdeficient by IHC. 1 This difference in MSI results could be caused by our distinct sample sets or differing sensitivity of the two MSI analysis methods.…”

TP53 Abnormalities and MMR Preservation in 5 Cases of Proliferating Trichilemmal Tumours

“…MMR system is also likely to be a component in UVB-induced DNA damage repairment, and over-expression has been observed on occasion in SCC [57], although others failed to demonstrate a significant relationship [40]. MSH2, one of the principal components of the MMR system, is part of the TP53 repair mechanisms [55].…”

“…MMR, the other studied repair mechanism has a less evident relationship with UV, but there is indirect evidence supporting its role in UV repairment [38]. However, although its mutation is likely to contribute to squamous cell carcinoma (SCC) progression, MMR deficiency is unlikely to play a significant role in SCC carcinogenesis [40].…”

Detection of MSH2 Gene Methylation in Extramammary Paget’s Disease by Methylation-Sensitive High-Resolution Melting Analysis

“…In Merkel cell carcinoma (MCC), for instance, 10.9% of MCC patients had impaired MSH2 expression, while 16.1% of patients had reduced expression in at least one MMR protein [29]. According to Vasan et al's report [30], about 9.1% of cutaneous head and neck squamous cell carcinomas were defective in MMR expression. For patients with Muir-Torre syndrome (MTS), MSH2 was the most frequently mutated MMR gene, and about 90% of the MMR gene mutations in MTS were found in MSH2 [31,32].…”