Mismatch-repair loss and an inherited label
A fictional colorectal tumor shows absent MLH1 and PMS2 nuclear staining while stromal and lymphoid internal controls are convincingly positive. MSH2 and MSH6 are retained. A trainee immediately labels the patient as having a confirmed inherited Lynch syndrome and recommends that relatives be told they must carry the same defect. The record has not yet supplied relevant reflex testing, family assessment or a germline result. The supervising clinician asks the trainee to separate a valid tumor staining pattern from the source of that pattern. The case is not about declaring the IHC uninterpretable but about choosing the next level of appropriately counseled investigation.
1. What does the valid pattern establish?
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It supports loss of the relevant tumor protein expression within the assay context. It does not by itself establish an inherited pathogenic variant.
2. What distinction guides further work?
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Use the appropriate colorectal reflex pathway and genetic-risk assessment to evaluate sporadic and inherited explanations without assuming a family genotype from tumor IHC alone.