Fig. 1. HER2 membrane levels and Trastuzumab efficacy depend on CAV1 protein levels.

a Immunohistochemical (IHC) detection and scoring intensity of CAV1, immunofluorescence (IF) staining of HER2 (green color) and CAV1 (red color) in HER2-expressing gastric tumor tissues. CAV1 reactivity at the cell membrane of tumor cells was considered for IHC scoring; IHC 0/1 + : CAV1-low (patient #14 and patients #3–5). IHC 2 + /3 + : CAV1-high (patient #1 and patient #2). The graphs plot protein fluorescence intensity per unit area, calculated by quantifying IF images (mean ± S.E.M, n = 3). Scale bar, 50 μm. HER2 membrane levels are classified as high versus low based on quantification of IF staining shown in Supplementary Fig. 5. Patient 1 to Patient 33 are IDs for all HER2⁺ gastric tumor tissues analyzed in the study (Supplementary Fig. 4). b ⁸⁹Zr-labeled Trastuzumab (1 μCi, 0.25 μg) binding and internalization in NCIN87 GC cells wild-type (WT) and AGS, KATOIII, SNU1 GC sublines stably expressing HER2 (LV-HER2). c Kaplan–Meier analyses of CAV1 expression and GC disease outcome in patients treated with Trastuzumab. Patients with HER2⁺/CAV1^HIGH (blue color, n = 12 patients) phenotype have a worse survival than HER2⁺/CAV1^LOW (red, n = 34 patients). Log rank; p < 1 × 10⁻⁴. Source data are provided as a Source Data file.