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Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
[Biomarkers in solid tumors]
1Patológiai Tudományok Doktori Iskolája, Semmelweis Egyetem, Budapest, Hungary. zsulacz@chello.hu
Abstract:
In the past decade the revolutionary development of molecular technology contributed a lot to the increase of our knowledge on cancer. These informations led to the discovery and understanding of those key regulatory changes in the genesis and progression of malignancies that can serve as targets in tumor diagnostics and therapy. One of the main challenges in the research field is to identify the most important molecular networks, the molecular targets, the markers (biomarkers) which can predict therapeutic responsiveness in order to select the appropriate patients, as well as markers to judge the prognosis of the disease. The aims of our study approached some details of the biomarker area and reached certain conclusions: (1) The anti-EGFR therapy, used in the second line or even further, proved to be effective, providing clinical advantage (operability, regression) in 36% of patients carrying wild-type KRAS. G13D mutations were the most frequent among the KRAS-mutants, which, according to current data, could react to anti-EGFR therapy. (2) Extended immunohistochemical (IHC) analysis on colorectal cancer samples (using tissue microarray) found rather few correlations between the IHC estimation and the clinical characteristics related mainly to survival. According to the results with anti-EGFR antibodies in the diagnostic histological samples, the regulatory pathway which rules the proliferation of normal colonic mucosa is also present in colonic cancer cells. This finding is supported by the increased ativity of the downstream members (as RAS, RAF, ERK) of the EGFR signalling. (3) The level of D-dimer increased at least as much as the level of classical tumor markers in the early stages of tumor growth. D-dimer can be considered as a prognostic factor in tumor types studied (breast-, colorectal-, ovarian cancers) and its measurement is advised besides the classical markers. We hope that these results may contribute to the design of a more individual-based and more effective antitumor strategy.
Insights
Molecular diagnostics advance cancer care. Anti-EGFR therapy benefits KRAS wild-type patients, while D-dimer shows prognostic value in multiple cancers, aiding personalized treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Diagnostics
Background:
- Molecular technology advancements have significantly improved cancer knowledge.
- Understanding key molecular changes in cancer is crucial for diagnostics and therapy.
- Identifying molecular targets and biomarkers for patient selection and prognosis is a major research challenge.
Purpose of the Study:
- To investigate the role of biomarkers in predicting therapeutic response and prognosis.
- To evaluate the effectiveness of anti-EGFR therapy in relation to KRAS mutations.
- To explore the utility of D-dimer as a prognostic marker in various cancers.
Main Methods:
- Analysis of anti-EGFR therapy response in patients with wild-type KRAS.
- Immunohistochemical (IHC) analysis of colorectal cancer samples using tissue microarray.
- Assessment of D-dimer levels in early-stage tumor growth for breast, colorectal, and ovarian cancers.
Main Results:
- Anti-EGFR therapy showed clinical benefit in 36% of wild-type KRAS patients; G13D mutations were frequent among KRAS-mutants.
- IHC analysis revealed the EGFR signaling pathway is active in colon cancer, with increased downstream activity.
- D-dimer levels increased in early tumor stages, comparable to classical tumor markers, and showed prognostic value.
Conclusions:
- KRAS wild-type status is a predictor for anti-EGFR therapy response.
- The EGFR pathway is a viable target in colorectal cancer, and D-dimer is a potential prognostic biomarker.
- These findings support the development of individualized and more effective antitumor strategies.

