Abstract 2018: The co-expression of HER family members, EGFRvIII, putative stem cell marker CD44, and their prognostic significance in patients with glioblastoma

Abstract The aberrant expression and activation of HER family members is a known major oncogenic pathway for the proliferation, progression, and metastasis of a wide range of human malignancies including brain cancer. Despite numerous efforts to target EGFR, commonly dysregulated in glioblastoma, approaches directed against EGFR have not achieved the same degree of success as seen in other tumour types. The tumour heterogeneity and other redundant cell signalling pathways could be some of contributing factors to the treatment with the EGFR inhibitors. In this study, our aim was to examine the relative expression and prognostic significance of all members of the HER family, and the type III EGFR mutant (EGFRvIII) as well as the putative stem cell marker CD44, in patients with glioblastoma. The expression levels of wild-type EGFR (wtEGFR), HER2, HER3, HER4, EGFRvIII and CD44 were determined in tumour specimens from 80 patients by immunohistochemistry. The staining was scored at cut off value of >5%, 10%, 20% and 50% with positive staining, the intensity and the cellular location of immunostaining. The association between the expression level of the biomarkers and patient overall survival was evaluated using Chi-squared, Kaplan-Meier survival curves and log rank test. At cut-off value of >5% with positive staining, there was moderate to high expression of wtEGFR, HER2, HER3, HER4, EGFRvIII, and CD44 in 46%, 75%, 19%, 71%, 85%, and 95% of the cases examined, respectively. The cellular location of wtEGFR was found to be membranous and cytoplasmic, HER2 and HER3 predominantly cytoplasmic, whereas HER4 was membranous, cytoplasmic and nuclear. The expression of EGFRvIII was mainly cytoplasmic and nuclear and CD44 membranous. Interestingly, at a cut off value of >5% of tumour cells with staining, the expression of wtEGFR was accompanied with co-expression with HER2 (35%), HER3 (0%), HER4 (30%), EGFRvIII (36%), CD44 (44%), HER2/EGFRvIII (28%), HER2/CD44 (31%), EGFRvIII/CD44 (36%) of the cases examined. In 83% and 55% of the cases examined, there was co-expression of EGFRvIII with CD44 and HER2/HER4/CD44 respectively. With the exception of HER2 expression, at cut off values of >5% of tumour cells with staining, which was associated with better overall survival [HR=0.57 (p=0.038) in univariate , HR=0.56 (p=0.034) multivariate], there was no significant association between the expression of other members of the HER family, EGFRvIII and CD44 and overall survival in both univariate and multivariate analysis. Taken together, our results suggest that the co-expression of different members of the HER family, with EGFRvIII and CD44 occurs in patients with glioblastoma and warrants further investigation on the predictive value of these biomarkers and their potential as targets for therapeutic interventions with drugs targeting these receptors. Citation Format: Ermira Mulliqi, Said Khelwatty, Izhar Bagwan, Ahmad Kamaludin, Anna Morgan, Natalie Long, Keyoumars Ashkan, Helmout Modjtahedi. The co-expression of HER family members, EGFRvIII, putative stem cell marker CD44, and their prognostic significance in patients with glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2018.