MLH1 and neoplasm: The molecular mechanism for the strong association of BRAF variant with CRC harboring somatic MLH1 hypermethylation is incompletely understood but appears to be tissue/tumor-specific; unlike algorithms in use for CRC, BRAF immunohistochemistry or sequencing cannot be used as a proxy for somatic MLH1 hypermethylation in gynecological cancers, as oncogenic BRAF variants occur so rarely in these.41 Therefore, moving straight to germline NGS on the basis of IHC MLH1 loss is also an option, although an expensive one.