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Published on: October 30, 2013
Most human granulosa cell tumors express c-MET: A potential new therapeutic target
Edina A Wappler-Guzzetta1,2, Daniel M Real1,3, Shehla Aman1
11Department of Pathology, Loma Linda University Medical Center, Loma Linda, CA 92354, USA.
Objectives:
The transmembrane receptor tyrosine kinase c-MET has a central role in granulosa cells in many physiological and pathological processes of granulosa cells, including cell survival and folliculogenesis. We therefore hypothesized that c-MET may be expressed in granulosa cell tumors (GCTs).
Methods:
c-MET immunostaining was performed retrospectively on human GCT specimens, including adult (n = 19) and juvenile GCTs (n = 2). Data was collected on patient demographics, tumor stage, and size. Furthermore, staining intensity was analyzed by a staining intensity score, and the presence or absence of membranous staining was noted. Multivariate logistic regression was used for statistical analysis, with P < 0.05 being considered statistically significant. Juvenile GCTs were excluded from the statistical analysis.
Results:
Both cytoplasmic and membranous staining was seen in GCT tissues, with the majority (∼74%) of the adult and both juvenile cases showing positive membranous staining. As expected, vascular endothelial cells were also c-MET positive in the tumor tissue. Amongst the adult GCT patients, tumor mitotic activity was higher with older age (r = 0.531; P = 0.019). Also, smaller tumors had higher c-MET intensity scores (r = -0.579, P = 0.038).
Conclusions:
Most GCTs were c-MET positive by immunostaining along with the vascular endothelial cells, highlighting the potential of c-MET inhibition as a therapeutic option in these tumors.
Insights
The transmembrane receptor tyrosine kinase c-MET is expressed in most granulosa cell tumors (GCTs), suggesting c-MET inhibition could be a potential therapeutic strategy for GCTs.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The transmembrane receptor tyrosine kinase c-MET plays a key role in granulosa cell survival and folliculogenesis.
- Given its function, c-MET expression was investigated in granulosa cell tumors (GCTs).
Purpose of the Study:
- To investigate the expression of c-MET in human granulosa cell tumors.
- To assess the potential of c-MET as a therapeutic target in GCTs.
Main Methods:
- Retrospective analysis of c-MET immunostaining in adult (n=19) and juvenile (n=2) GCT specimens.
- Data collection included patient demographics, tumor stage, and size.
- Statistical analysis using multivariate logistic regression (P < 0.05).
Main Results:
- Positive membranous c-MET staining was observed in approximately 74% of adult GCTs and 100% of juvenile GCTs.
- Vascular endothelial cells within the tumor tissue also showed c-MET positivity.
- Higher tumor mitotic activity correlated with older age in adult GCT patients (r = 0.531, P = 0.019).
- Smaller tumors exhibited higher c-MET intensity scores (r = -0.579, P = 0.038).
Conclusions:
- The majority of GCTs demonstrate c-MET positivity.
- Co-expression of c-MET in tumor-associated vascular endothelial cells was noted.
- These findings suggest that c-MET inhibition represents a promising therapeutic avenue for GCTs.
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