Third, although RB1 protein can be expressed as an inactive form when tumor cells harbour missense mutation in RB1 gene or HPV-mediated RB1 inactivation which makes it difficult for IHC to classify RB1 functional status, the CCND1/CDKN2A ratio expression assay could detect various types of RB1 functional inactivation as shown in Figure 1 and 2. The gene discussed is CDKN2A; the disease is neoplasm.