Abstract 5152: Co-expression and prognostic significance of HER family members and EGFRvIII in patients with hepatocellular carcinoma
Authors: Ozlem Sherif, Said Khelwatty, Izhar Bagwan, Alan Seddon, Angus Dalgleish, Satvinder Mudan, Helmout Modjtahedi
Journal: Cancer Research (2024)

Abstract Hepatocellular carcinoma is one of the most common type of liver cancer. Despite advances in its treatment including the approval of several targeted agents in the past few decades, many patients do not respond or have a response of short duration to such therapeutic interventions. As a result, liver cancer is the third leading cause of cancer-related deaths worldwide. Therefore, it is essential to identify additional therapeutic targets and to develop more effective therapeutic interventions. In the past few decades, increased expression, and activation of the human epidermal growth factor receptor (HER) family members have been detected in various cancer types and of these, EGFR and HER2 are important therapeutic targets for the treatment of patients with a wide range of cancers, but currently not in liver cancer. In some studies, cross-talk between different members of the HER family has been associated with tumor progression and resistance to therapy with EGFR inhibitors but there has been no comprehensive study of the expression of all members of the HER family in patients with hepatocellular carcinoma. In this study, we examined the relative expression of all members of the HER family, type-III deletion mutant of EGFR (i.e.EGFRvIII), which is a tumor specific antigen, and two putative liver cancer cell biomarkers (i.e. CD44, EpCAM) in 43 patients with hepatocellular carcinoma by immunohistochemistry. The prognostic significance of such antigens was also investigated. Of these, the expression of EGFR, HER2, HER3, HER4 and EGFRvIII was found in tumor specimens from 35%, 58%, 0%, 19%, and 26% of the cases, respectively. Interestingly, at a cut off value of &amp;gt;5% of tumor cells with staining, 23%, 14% and 9% of the patients had co-expression of EGFR with HER2, EGFRvIII, and HER2/EGFRvIII. In addition, 40% and 33% of the cases were CD44 and EpCAM positive. Of these, the expression of EGFRvIII positivity at &amp;gt;5% ( HR=3.35, p=0.002) and 20% (HR=7.22, p=0.003) of tumour cells and membranous CD44 ( HR=2.12, p=0.04) were associated with a poorer survival in patients with hepatocellular carcinoma. In contrast, the expression of cytoplasmic CD44 was associated with a better overall survival (HR=0.30, p=0.02). These were found to be independent prognostic markers in multivariate analysis. Interestingly, the co-expression of EGFR with EGFRvIII was associated with a poorer overall survival (59.5 vs 21.0 months, p=0.004). Taken together, our results suggest that the expression of EGFRvIII occurs in patients with hepatocellular carcinoma and highlight its importance as biomarker for tumor progression and as a potential target for therapeutic intervention with drugs targeting EGFRvIII and other members of HER family. Citation Format: Ozlem Sherif, Said Khelwatty, Izhar Bagwan, Alan Seddon, Angus Dalgleish, Satvinder Mudan, Helmout Modjtahedi. Co-expression and prognostic significance of HER family members and EGFRvIII in patients with hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5152.