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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Differential expression of c-Met, its ligand HGF/SF and HER2/neu in DCIS and adjacent normal breast tissue
K Lindemann1, J Resau, J Nährig
1Department of Obstetrics and Gynaecology, Technical University, Munich, Germany.
Aims:
Tyrosine kinase receptors Her2/neu and c-Met play an important role in breast cancer development and progression. Our aim was to determine the expression of c-Met, its ligand hepatocyte growth factor/scatter factor (HGF/SF) and Her2/neu in ductal carcinoma in situ (DCIS) lesions of the breast (n = 39) by two different immunocytochemical techniques, classical immunohistochemistry and immunofluorescence, and to correlate their expression levels with histopathological and clinical characteristics.
Methods And Results:
Both methods revealed similar c-Met staining patterns in both the in situ component and the adjacent normal tissue (P < 0.001). However, an imbalance in c-Met expression between tumour and surrounding normal tissue was correlated with high-grade DCIS (Van Nuys Grade 3). No correlation existed between Her2/neu and c-Met expression. High HGF/SF immunoreactivity was observed in 43.6% of the cases, yet the adjacent cellular stroma revealed only low levels of HGF/SF. No correlation existed between c-Met, Her2/neu or HGF/SF expression and clinicopathological factors.
Conclusion:
An imbalance in c-Met expression between tumour and surrounding normal tissue is associated with an aggressive DCIS phenotype. Moreover, c-Met and HGF/SF may contribute to tumour development by different means than those controlled by Her2/neu.
Insights
An imbalance in c-Met receptor expression between tumor and normal breast tissue is linked to aggressive ductal carcinoma in situ (DCIS). c-Met and HGF/SF may drive tumor development independently of Her2/neu.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tyrosine kinase receptors Her2/neu and c-Met are implicated in breast cancer progression.
- Understanding their role in ductal carcinoma in situ (DCIS) is crucial for early detection and treatment.
Purpose of the Study:
- To investigate the expression of c-Met, hepatocyte growth factor/scatter factor (HGF/SF), and Her2/neu in DCIS.
- To correlate these expressions with histopathological and clinical features.
Main Methods:
- Utilized two immunocytochemical techniques: classical immunohistochemistry and immunofluorescence.
- Analyzed 39 cases of breast DCIS lesions.
Main Results:
- Demonstrated consistent c-Met staining patterns between tumor and normal tissue using both methods.
- Found a correlation between c-Met expression imbalance and high-grade DCIS (Van Nuys Grade 3).
- Observed high HGF/SF immunoreactivity in tumors, contrasting with low levels in adjacent stroma; no correlation with clinicopathological factors was found.
Conclusions:
- An imbalance in c-Met expression between tumor and surrounding tissue is associated with an aggressive DCIS phenotype.
- c-Met and HGF/SF may contribute to tumor development through mechanisms distinct from Her2/neu pathways.
