KDM6A IHC: A New Tool for Low-Grade Urothelial Neoplasia Detection

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KDM6A is a histone-modifying protein that is strongly expressed in virtually all human cell types. KDM6A expression loss is a common feature in low-grade non-invasive urothelial carcinomas of the urinary bladder.

In a groundbreaking study, Viehweger et al. described the usefulness of KDM6A immunohistochemistry (IHC) using clone HMV311 in detecting neoplastic urothelial cells. The authors demonstrate that KDM6A expression is completely lost in 22.8% of urothelial carcinomas. As KDM6A losses predominantly occur in non-invasive and low-grade cancers (≥35.7% of low-grade pTa tumours), KDM6A IHC is likely to aid the detection of low- and intermediate-grade tumour cells, which cannot always be distinguished by morphology alone. Complete KDM6A loss is easily recognisable, as virtually all normal cell types express KDM6A at high levels, and positive internal controls are always present.

KDM6A (lysine demethylase 6A, also known as UTX) is an epigenetic regulator that is often found to be mutated in cases of urothelial carcinoma. As KDM6A is located on chromosome X and most KDM6A mutations are truncating, they usually result in complete loss of protein expression, which can be detected by immunohistochemistry (IHC).
In their study, Viehweger et al. described KDM6A expression loss in 35.7% of pTaG2 low-grade, 23% of pTaG2 high-grade, 18.5% of pTaG3 and 19.9% of pT2-4 urothelial carcinomas of the urinary bladder. As the study used tissue microarrays and excluded negative samples without positive internal control cells, the true numbers may be higher still.
Due to the high level of KDM6A expression in normal cells and the complete absence of KDM6A expression in tumour cells, KDM6A expression losses may also be detectable in urine specimens.

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