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Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
Published on: October 25, 2011
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Intratumor morphologic and transcriptomic heterogeneity in V600EBRAF-mutated metastatic colorectal adenocarcinomas
V Angerilli1, E Fontana2, S Lonardi3
1Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy.
ESMO Open
|July 16, 2021
Summary
Intratumor heterogeneity (ITH) in colorectal cancer, particularly in BRAF-mutated cases, is linked to molecular changes and impacts treatment. Assessing both morphologic and molecular ITH is crucial for personalized cancer therapy.
Area of Science:
- Oncology
- Pathology
- Molecular Biology
Background:
- Intratumor heterogeneity (ITH) involves diverse tumor cell clones, driving drug resistance.
- Accurate ITH assessment is vital for developing effective cancer therapies.
Purpose of the Study:
- To dissect morphologic and molecular intratumor heterogeneity in colorectal adenocarcinoma.
- To investigate the association between heterogeneity and key molecular markers.
Main Methods:
- Evaluated 120 BRAF-mutated colorectal adenocarcinomas for morphologic heterogeneity.
- Characterized heterogeneous components via histopathology, immunohistochemistry, and molecular profiling (KRAS/BRAF/NRAS mutations, MSI, CMS).
Main Results:
- 25.8% of tumors showed heterogeneous morphology.
- Of 8 cases with molecular profiling, 62.5% were microsatellite unstable (MSI) and 62.5% exhibited a CMS4 phenotype.
- Heterogeneity in consensus molecular subtype (CMS) was noted in 50% of cases.
Conclusions:
- Morphologic and molecular ITH, including CMS changes, occur in BRAF-mutated colorectal cancer.
- ITH may influence treatment response and clinical outcomes.
- Integrating ITH assessment into pathology reports can improve cancer classification and treatment tailoring.
