Ovarian Granulosa Cell Tumor: New Insights into the Clinical Challenge of Late Relapsee
Abstract
Adult granulosa cell tumor (AGCT) is a unique subtype of ovarian cancer that accounts for 5% of all ovarian malignancies. AGCTs are diagnosed typically in perimenopausal women, suggesting that elevated serum gonadotropin levels may contribute to tumor development. The 5-year survival is 90-97% for patients with Stage I AGCT but is significantly worse for patients with higher stage or recurrent disease. The ostensibly favorable 5-year survival for individuals with low stage AGCT belies the major clinical problem of late relapse; one-third of women with Stage Ic AGCT suffer a relapse 6-8 years after initial diagnosis. Given the propensity for AGCT to relapse years after the initial diagnosis, more effective adjuvant therapies and surveillance strategies are needed. The objective of this two-year Ovarian Cancer Research Program (OCRP) Pilot Award was to explore whether hormonal modulation therapy may be beneficial in treatment of ACGT. Aim 1 of the project focused on development of a new xenograft model to assess the impact of estrogen replacement therapy and gonadotropin suppression therapy on the growth of AGCTs. Unfortunately, technical obstacles were encountered xenograft growth, limiting the conclusions that could be drawn from this portion of the study. Aim 2used a large database of clinical specimens to evaluate the expression of druggable hormone targets in samples from patients with AGCT. We found that: 1) follicle stimulating hormone receptor (FSHR) is widely expressed in AGCTs, 2) serum follicle stimulating hormone (FSH) and inhibin B levels correlated inversely, suggesting that tumor-derived inhibin B affects pituitary FSH secretion, 3)CYP19A1 is expressed in a subset of AGCTs, and 4) ER is the main estrogen receptor in AGCTs and its expression is higher in recurrent tumors. Our study cohort was larger than any reported in the medical literature.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2018
- Accession Number
- AD1074307
Entities
People
- David B. Wilson
Organizations
- Washington University in St. Louis