Tumour mismatch repair protein loss is associated with advanced stage in oral cavity squamous cell carcinoma

Abstract

An unexplained increase in the incidence of oral cavity squamous cell carcinoma (oSCC) has been observed despite decreasing smoking rates, particularly in younger patients. Links to defects in the DNA mismatch repair (MMR) system are well established in early onset colorectal, urothelial and gynaecological malignancies. MMR deficient patients treated with immune checkpoint inhibitors have demonstrated improved response rates. Studies exploring MMR status in head and neck squamous cell carcinoma (HNSCC) demonstrate conflicting results. This study explores the incidence of MMR protein loss and its association with clinicopathological features and outcome in oSCC. Immunohistochemical staining using tissue microarrays to assess the expression of MMR proteins (hMLH1, hMSH2, hMSH6, and hPMS2) was performed on 285 consecutive oSCC cases between 2000 and 2016. Data on smoking, alcohol and metachronous malignancies were retrospectively collected. Proportional hazards regression models were used to compare survival in MMR intact and deficient patients. MMR deficiency was seen in 21 patients (7.4%). MMR deficient tumours were associated with bone invasion (52% vs 32%, p=0.05), higher pT stage (pT4 in 57% vs 35%, p<0.001) and a higher number of metachronous malignancies (p=0.05). MMR deficiency was not associated with younger age at presentation or absence of smoking or alcohol. There was no significant association between MMR status and survival (overall survival hazard ratio 1.36; p=0.32). The incidence of MMR loss in oSCC is low and is not associated with young age at presentation. MMR deficiency in oSCC is associated with an increase in the number of metachronous malignancies and more advanced primary tumours.