Serum Müllerian Inhibiting Substance/Anti-Müllerian Hormone levels in patients with adult granulosa cell tumors directly correlate with aggregate tumor mass as determined by pathology or radiology

Abstract

Objectives Granulosa cell tumors (GCTs) comprise 2–5% of ovarian tumors. Serum Müllerian Inhibiting Substance (MIS, also known as anti-Müllerian Hormone, or AMH) levels have been validated as a marker of GCT recurrence and progression. There has been little correlation between serum MIS/AMH levels several clinical parameters in GCTs, including tumor burden. We have performed a retrospective review correlating aggregate tumor mass as reported by pathologic examination or by radiology with serum MIS/AMH levels drawn on the date of examination. Methods We retrospectively identified 32 GCT patients at our institution over the last 15 years who had serum MIS/AMH measurements. Patients who had serum MIS/AMH measurements within three days of surgery or on the same day as abdominal computerized tomography scan (CT) or magnetic resonance imaging (MRI) were further evaluated. Results We found a significant direct correlation between patient serum MIS/AMH levels and gross aggregate tumor mass determined by pathology (slope=15.4±6.06, r=0.65, p<0.04) or by radiographic aggregate tumor mass for all data points identified (slope=0.07±0.03, r=0.33, p<0.04) and after correcting for selection bias (slope=1.45±0.17, r=0.93, p<0.01). We also identified a significant difference between serum MIS/AMH levels between samples drawn the same day as negative and positive abdominal CT or MRI scans (8.16±1.54 vs. 158.7±32.2 ng/ml, p<0.0001). Conclusions These data indicate a significant direct correlation between serum MIS/AMH levels and both gross and radiographic aggregate tumor mass in GCT patients. Together with the current literature, the present data argues for a more prominent role for serum MIS/AMH in the management of GCTs.

Constitutive Activation of PI3K in Oocyte Induces Ovarian Granulosa Cell Tumors

“…To test if high p-AKT levels in GCTs reflected the altered endocrine profile of Cre+ mice, serum hormone levels were examined. AMH, a marker for GCTs (36), was significantly higher in Cre+ mice (Fig. 2D).…”

Anti-Müllerian hormone inhibits growth of AMH type II receptor-positive human ovarian granulosa cell tumor cells by activating apoptosis

“…[34][35][36] In human GCTs, serum AMH levels have been shown to positively correlate with the tumor size, ie, the bigger the tumor the higher the serum AMH levels. 57 While there is a controversy of high serum but low tissue AMH in the large human GCTs, it can be presumed that in a subset of tumors of certain size the AMH level in the microenvironment may be lower than required to sustain the growth inhibition of granulosa cells. Features of this GCT subgroup, thus, closely reflect the highly proliferating granulosa cells of large antral AMH activates apoptosis in human ovarian GCTs M Anttonen et al follicles, which exhibit downregulated AMH expression, 58 suggesting a positive selection process of these cells with increased growth potential.…”

Müllerian inhibiting substance/anti-Müllerian hormone: A novel treatment for gynecologic tumors

“…The vast majority of sex cord and granulosa cell tumors [86,87] secrete MIS/AMH in proportion to tumor burden [88] and changes in serum MIS/AMH reflect recurrences and/or response to therapy. These tumors may express the MIS/AMH receptor [89] but the tumors are not responsive to the MIS/AMH they produce.…”