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Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis
Published on: May 12, 2019
Receptor Tyrosine Kinase Pathway and Infiltrating Urothelial Carcinoma
Seyma Buyucek1, Sinem Kantarcioglu Coskun1, Binnur Onal1
1Department of Pathology and Cytology, School of Medicine, Duzce University, Konuralp Campus, Duzce, Turkey.
Abstract:
Receptor tyrosine kinase pathway is frequently searched for cancer causing mutations in tumors. Emerging targeted therapies are gleam of hope for them. Infiltrating urothelial carcinoma can have many morphological aspects according to their differentiation/variants. To evaluate KRAS, BRAF, and PIK3CA mutations and HER2, EGFR, and p16 expression, we divided urothelial carcinomas into two groups: differentiated/variants (n = 12) and conventional (n = 12). We compared results with clinical, demographic, histopathologic features and survival rates. No statistically significant results could be obtained in the comparison of histopathologic properties/survival rates with mutation analysis and EGFR, HER2, and p16 status. Differentiated/variants urothelial carcinoma showed higher EGFR expression (P < 0.001). Glandular differentiation was the most frequent type, followed by squamous and sarcomatoid differentiation. We observed the most common mutation at KRAS with a propensity for urothelial carcinoma with glandular differentiation. More than one mutation/high protein expression was seen in some tumors. Targeted therapies for KRAS mutation can be effective at urothelial carcinoma with glandular differentiation. Heterologous expression of relevant proteins and genes can be a cause for targeted treatment obstacle. The determination of the molecular characters of tumors is a guide in creating targeted treatment algorithms and in choosing the patient.
Insights
Investigating urothelial carcinoma, this study found KRAS mutations are common, especially in glandular subtypes. These findings may guide targeted therapies for specific urothelial cancer variants.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Receptor tyrosine kinase (RTK) pathway mutations are crucial in cancer development.
- Targeted therapies offer new hope for cancer treatment.
- Urothelial carcinoma exhibits diverse morphological features based on differentiation and variants.
Purpose of the Study:
- To evaluate KRAS, BRAF, and PIK3CA mutations and HER2, EGFR, and p16 expression in urothelial carcinoma.
- To compare these molecular findings with clinical, demographic, histopathologic features, and survival rates.
- To identify potential targets for personalized medicine in urothelial carcinoma.
Main Methods:
- Urothelial carcinomas were divided into differentiated/variants (n=12) and conventional (n=12) groups.
- Analysis included KRAS, BRAF, PIK3CA mutations and HER2, EGFR, p16 expression.
- Statistical comparisons were made with clinical, histopathologic, and survival data.
Main Results:
- No significant correlation found between histopathology/survival and mutation/protein status.
- Differentiated/variants urothelial carcinoma showed significantly higher EGFR expression (P < 0.001).
- KRAS mutations were most common, particularly in urothelial carcinoma with glandular differentiation.
Conclusions:
- KRAS mutations are prevalent in urothelial carcinoma, especially with glandular differentiation, suggesting potential for targeted KRAS-directed therapies.
- Higher EGFR expression in differentiated/variants subtypes warrants further investigation.
- Molecular characterization is essential for developing targeted treatment algorithms and patient selection.
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