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Updated: May 18, 2026
Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
Tyrosine kinase receptor status in endometrial stromal sarcoma: an immunohistochemical and genetic-molecular analysis
Paolo Cossu-Rocca1, Marcella Contini, Maria Gabriela Uras
1Departments of Clinical and Experimental Medicine, Biomedical Sciences, University of Sassari, Sassari, Italy. pcossurocca@yahoo.it
Abstract:
Endometrial stromal sarcomas (ESS) are rare uterine malignant mesenchymal neoplasms, which are currently treated by surgery, as effective adjuvant therapies have not yet been established. Tyrosine kinase inhibitors have rarely been applied in ESS therapy, with few reports describing imatinib responsivity. The aim of this study was to analyze the status of different tyrosine kinase receptors in an ESS series, in order to evaluate their potential role as molecular targets. Immunohistochemistry was performed for EGFR, c-KIT, PDGFR-α, PDGFR-β, and ABL on 28 ESS. EGFR, PDGFR-α, and PDGFR-β gene expression was investigated by real-time polymerase chain reaction (qRT-PCR) on selected cases. "Hot-spot" mutations were screened for on EGFR, c-KIT, PDGFR-α, and PDGFR-β genes, by sequencing. All analysis was executed from formalin-fixed, paraffin-embedded specimens. Immunohistochemical overexpression of 2 or more tyrosine kinase receptors was observed in 18 of 28 tumors (64%), whereas only 5 tumors were consistently negative. Gene expression profiles were concordant with immunohistochemical overexpression in only 1 tumor, which displayed both high mRNA levels and specific immunoreactivity for PDGFR-α, and PDGFR-β. No activating mutations were found on the tumors included in the study. This study confirms that TKRs expression is frequently observed in ESS. Considering that the responsiveness to tyrosine kinase inhibitors is known to be related to the presence of specific activating mutations or gene over-expression, which are not detectable in ESS, TKRs immunohistochemical over-expression alone should not be considered as a reliable marker for targeted therapies in ESS. Specific post-translational abnormalities, responsible for activation of TKRs, should be further investigated.
Insights
Endometrial stromal sarcomas (ESS) frequently show tyrosine kinase receptor (TKR) expression, but lack the activating mutations or gene overexpression needed for targeted therapies. Further research into post-translational abnormalities is required for effective treatment development.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Endometrial stromal sarcomas (ESS) are rare uterine cancers with limited effective adjuvant therapies.
- Tyrosine kinase inhibitors (TKIs) have shown minimal success in ESS, with few documented responses to imatinib.
- Understanding TKR status in ESS is crucial for identifying potential molecular targets.
Purpose of the Study:
- To analyze the expression of various tyrosine kinase receptors (TKRs) in a series of ESS.
- To evaluate the potential of these TKRs as molecular targets for novel therapeutic strategies.
- To investigate the correlation between TKR expression, gene expression, and mutational status in ESS.
Main Methods:
- Immunohistochemistry (IHC) was performed on 28 ESS specimens to assess EGFR, c-KIT, PDGFR-α, PDGFR-β, and ABL.
- Gene expression analysis using quantitative real-time polymerase chain reaction (qRT-PCR) for EGFR, PDGFR-α, and PDGFR-β.
- Sequencing to screen for "hot-spot" mutations in EGFR, c-KIT, PDGFR-α, and PDGFR-β genes.
Main Results:
- Overexpression of two or more TKRs was detected in 64% (18/28) of ESS tumors via IHC.
- Gene expression profiles showed concordance with IHC overexpression in only one case (PDGFR-α and PDGFR-β).
- No activating mutations were identified in the screened TKR genes within the study cohort.
Conclusions:
- While TKR expression is common in ESS, the absence of detectable activating mutations or significant gene overexpression limits their utility as direct targets for current TKIs.
- Immunohistochemical overexpression of TKRs alone is not a reliable indicator for guiding targeted therapy selection in ESS.
- Further investigation into specific post-translational abnormalities driving TKR activation is necessary for developing effective targeted treatments for ESS.
