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Tyrosine kinase expression in pulmonary metastases and paired primary tumors
Bernd M Muehling1, Sara Toelkes, Hubert Schelzig
1Department of Thoracic and Vascular Surgery, University of Ulm, Steinhövelstrasse 9, 89075 Ulm, Germany. bernd.muehling@uniklinik-ulm.de
Abstract:
Tyrosine kinase inhibitors against the receptors of vascular endothelial growth factor (VEGFR), epidermal growth factor (EGFR) and the platelet derived growth factor (PDGFR) are increasingly used in the treatment of progressive cancers. However, the expression of these receptors especially in lung metastases has not been examined. Tissue specimen from 35 lung metastases of 33 patients with renal cell carcinoma (n=8), sarcoma (n=10), colorectal carcinoma (n=6), otolaryngologic carcinoma (OLC, n=4), testicular and endometrial cancer (n=1 each), malignant melanoma (n=1), adrenal cancer (n=2), malignant fibrous histiocytoma and malignant peripheral nerve sheath tumor (n=1 each) have been immunohistochemically tested for the expression of PDGFR alpha/beta, VEGFR and EGFR. None of the patients had been pretreated with angiogenic inhibitors prior to metastasectomy. PDGFRalpha was expressed in all metastases; 31% stained negative for PDGFRbeta, 86% negative for VEGFR and 45% negative for EGFR. Primary tumors revealed positive staining for PDGFRalpha in 88%, for PDGFRbeta in 59%, for VEGFR in 0% and for EGFR in 18%. Our investigation of a pilot character represents a 'biomarker-based' analysis of pulmonary metastases of different primary tumors; we conclude that an immediate 'tumor profiling' at initial diagnosis should be considered in order to guide tumor therapy individually.
Insights
Targeted cancer therapies like tyrosine kinase inhibitors are common. This study examined receptor expression in lung metastases, finding PDGFRalpha universally present, suggesting personalized tumor profiling for effective treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Tyrosine kinase inhibitors targeting VEGFR, EGFR, and PDGFR are vital in advanced cancer treatment.
- Receptor expression in lung metastases remains underexplored, hindering targeted therapy selection.
Purpose of the Study:
- To investigate the expression of PDGFR alpha/beta, VEGFR, and EGFR in lung metastases from various primary cancers.
- To assess the potential of these receptors as biomarkers for guiding individualized cancer therapy.
Main Methods:
- Immunohistochemical analysis of 35 lung metastases from 33 patients with diverse primary tumors.
- Patients had not received prior anti-angiogenic therapy before metastasectomy.
Main Results:
- PDGFRalpha was expressed in all analyzed lung metastases.
- PDGFRbeta, VEGFR, and EGFR showed variable expression (negative in 31%, 86%, and 45% of cases, respectively).
- Primary tumors exhibited different expression patterns compared to metastases, with VEGFR notably absent in primary tumors.
Conclusions:
- PDGFRalpha is a ubiquitous marker in lung metastases, indicating its potential as a therapeutic target.
- Tumor profiling at initial diagnosis is crucial for tailoring treatment strategies and improving patient outcomes.
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