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• W2500955413 abstract "Background: Codrituzumab/GC33/RO5137382 is a recombinant humanized monoclonal antibody against Glypican-3 (GPC3) which is highly expressed in HCC cells. As part of phase I clinical trial, GC-002US study, evaluating escalating doses of codrituzumab plus sorafenib in HCC, immunofluorescent staining of GPC3 were applied in addition to GPC3 immunohistochemistry (IHC) with conventional DAB staining. The objectives of this work were to compare GPC3 expression levels by different staining methods and evaluate the correlation between these GPC3 scores and codrituzumab activities. Methods: Biopsies specimens (n = 34) collected at baseline in the phase I trial were evaluated by GPC3-IHC and immunofluorescent quantification digital slide (IQD) methods. GPC3-IHC were conducted using mouse anti-human GPC3 antibody, mouse GC33 (Ventana Medical Systems) as reported previously (Ikeda M. et al., Cancer Sci. 2014: 105; 455-462) and H scores were derived by two pathologists. For IQD, biopsy specimens were stained with same primary antibody, and were incubated with Qdot 655-conjugated secondary antibody. Fluorescent images of whole slides were obtained with the Nano-Zoomer (Hamamatsu Photonics K. K.). The IQD intensity score (immunofluorescent intensity per pixel) and cell score (immunofluorescent intensity per cell) were calculated respectively using MatLab (MathWorks Inc.). Results: There was a statistically significant correlation between GPC3 H scores and IQD scores. Among GPC3 scores, only the IQD cell score was correlated with serum GPC3 C-terminus increase by treatment (p = 0.032), whereas in the patients treated with higher dose of GC33 (≥ 10 mg/kg/week) the cytoplasmic H and the IQD intensity score were also correlated with serum GPC3 C-terminus increase by treatment. Interestingly, increasing cut-off values of IQD cell score levels led to lower HR and longer PFS. Best HR with lowest p value was observed at a cut-off value of 66,183 (HR = 0.24, p = 0.038). Conclusion: This study suggested that higher GPC3 expression on HCC cells quantified by IQD method was superior to other scores to predict codrituzumab activity, though this analysis was conducted only with limited number of subjects assessed. Further assessment and validation in clinical study of codrituzumab would be necessary to make a final conclusion on the clinical application of GPC3 IQD. Citation Format: Takayoshi Tanaka, Yasuo Sugitani, Tokiya Abe, Miho Kawaida, Ken Yamazaki, Akinori Hashiguchi, Michiie Sakamoto, Toshihiko Ohtomo. Immunofluorescent digital slide technology to evaluate correlation between Glypican-3 expression and response to codrituzumab. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 409." @default.
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• W2500955413 date "2016-07-15" @default.
• W2500955413 modified "2023-09-27" @default.
• W2500955413 title "Abstract 409: Immunofluorescent digital slide technology to evaluate correlation between Glypican-3 expression and response to codrituzumab" @default.
• W2500955413 doi "https://doi.org/10.1158/1538-7445.am2016-409" @default.
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