32P Comparison of fully automated microsatellite instability test to immunohistochemistry for mismatch repair protein expression in endometrial carcinoma

Abstract

Results: 375 samples were profiled for HRD status and were divided into four tiers based on the weight of HRD-related mutation pattern. Cox model showed significant survival difference (p-value ¼ 0.001) proportional to the weight of HRD mutation pattern with higher weight being the longest survival and vice versa. 223 and 152 samples were categorized as HRD and non-HRD based on optimized threshold and survival difference remains significant (p-value ¼ 0.0017). Similar survival difference was observed (p-value¼0.0013) suggesting the validity of the method on targeted sequencing. Out of 124, 49 and 19 breast, ovarian and prostate cancer samples, 13, 11 and 4 of them were labeled as HRD positive based on known HRD causing variants. All but one HRD positive samples were consistently classified by our method.Conclusions: Our results showed that NMF method is able to faithfully detect HRD samples. The method can be applied to WES as well as targeted sequencing and achieve equally significant survival difference between samples with different HR status. Upon detecting HRD, this method can identify additional HRD patients and therefore make better patient stratification.