Most human granulosa cell tumors express c-MET: A potential new therapeutic target

Wappler-Guzzetta, Edina A. and Real, Daniel M. and Aman, Shehla and Huang, Chelsea and Deisch, Jeremy K. and Denham, Laura J. (2026) Most human granulosa cell tumors express c-MET: A potential new therapeutic target. PHYSIOLOGY INTERNATIONAL, 113 (2). pp. 299-310. ISSN 2498-602X

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Abstract

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 5 19) and juvenile GCTs (n 5 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 5 0.531; P 5 0.019). Also, smaller tumors had higher c-MET intensity scores (r 5 0.579, P 5 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.

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