Extended Data Fig. 6: Loss of RB promotes alternative pathways towards gaining metastatic competency.
From: RB constrains lineage fidelity and multiple stages of tumour progression and metastasis
a, H&E photomicrographs of metastases that formed from KP;RbTR/TR tumours. b, Immunofluorescence analysis of KP and KP;RbTR/TR tumours for co-expression of HMGA2 and NKX2-1. c, Immunohistochemistry staining of serial sections from KP and KP;RbTR/TR tumours for HMGA2 and FOXA2. Orange dotted lines outline mutually exclusive staining and red dotted lines outline co-expressing staining patterns. Quantification of staining pattern (right) showing percentages of HMGA2+ tumours from KP or KP;RbTR/TR mice that are FOXA2+ or FOXA2−. KP, n = 29 tumours from 3 mice; KP;RbTR/TR, n = 37 tumours from 3 mice. Significance was determined by two-sided χ2 test. P = 1.1 × 10−5. d, Left, histological analysis of KP;RbTR/TR metastases. H&E staining and immunohistochemistry for NKX2-1, HMGA2 and FOXA2 of serial sections from representative metastases that are NKX2-1+ or NKX2-1−. Right, quantification. e, Immunohistochemistry staining of KP and KP;RbTR/TR tumours for club (CC10) and neuroendocrine (synaptophysin) cell markers. For control and comparison, a synaptophysin-positive small-cell lung cancer from a Trp53flox/flox;Rbflox/flox;p130flox/flox mouse model is shown.
