Figure 2.

p16 and cyclin D1 as ancillary markers of Rb functional status. A, Violin dot-plot graph depicting p16 and cyclin D1 H-scores in relation to groups defined by Rb expression and RB1 alterations, and demonstrating a consistent p16^high/cyclin D1^low profile for Rb^lost and Rb^exp/RB1^mut tumors, whereas all Rb^exp/RB1^WT tumors demonstrated the opposite p16^low profile, with cyclin D1^high in most cases. †, Rb-lost group in this analysis included 25 cases from the current cohort and 77 cases from TMAs (see Materials and Methods). Statistical significance: ***, P < 0.0001. B, Heatmap of Rb^exp/RB1^WT cases summarizing the incidence of p16^low (H-score ≤ 100) and cyclin D1^high (H-score ≥ 50), with the thresholds defined using the distribution of scores in Rb-lost SCLC (see Supplementary Table S1). C, Photomicrographic examples of Rb, p16, and cyclin D1 profiles in SCLC groups defined by Rb expression and RB1 alterations. D, Violin dot-plot graph showing H-scores of Rb immunoexpression in RB1 wild-type (Rb^expRB1^WT) tumors compared with those with RB1 mutations (Rb^expRB1^MUT). Statistical significance: **, P = 0.0057. Exp, expressed; mut, mutated; WT, wild type.