Adult granulosa cell tumors of the ovary: a retrospective study of 30 cases with respect to the expression of steroid synthesis enzymes

J Gynecol Oncol. 2017 Jul;28(4):e31. doi: 10.3802/jgo.2017.28.e31.

Abstract

Objective: Some, but not all, granulosa cell tumors are characterized by estrogen production. This study was designed to determine whether there are clinical or pathological variations in granulosa cell tumors in relation to the expression of sex steroid synthesis enzymes.

Methods: Clinical symptoms, serum hormonal values, and histology of 30 granulosa cell tumor patients who underwent surgery between 2002 and 2014 were retrospectively reviewed.

Results: Most patients presented with abnormal genital bleeding including abnormal menstrual cycles. Eight of 16 patients older than 50 years had endometrial hyperplasia and one had endometrial cancer. Serum 17β-estradiol (E₂) levels tended to be higher in patients over 50 years of age (p=0.081). Serum follicle-stimulating hormone (FSH) levels were low in all patients irrespective of serum E₂ levels. Magnetic resonance imaging revealed a thicker endometrium in older as compared to younger patients (p<0.05). Tumor cells in the majority of cases were positive for inhibin α and P450 aromatase, irrespective of age and serum E₂ levels. P450 17α-hydroxylase (P450c17) expression varied among cases. P450c17 was strongly positive in luteinized tumor cells and weakly positive in theca cells and fibroblasts. High E₂ levels were associated with P450c17-positive cells in the tumor (p<0.05).

Conclusion: The expression of hormone-synthesizing enzymes divides granulosa cell tumors into 2 distinct types; tumors with P450c17-positive cells show elevated serum E₂ and related clinical symptoms, while tumors without these cells show symptoms related to FSH suppression by inhibin.

Keywords: Estrogens; Granulosa Cell Tumor; Ovary; Steroid Hydroxylases.

MeSH terms

  • Aromatase / metabolism*
  • Endometrium / diagnostic imaging
  • Endometrium / pathology
  • Estradiol / blood
  • Female
  • Follicle Stimulating Hormone / blood
  • Granulosa Cell Tumor / blood
  • Granulosa Cell Tumor / enzymology*
  • Granulosa Cell Tumor / pathology
  • Humans
  • Inhibins / metabolism*
  • Magnetic Resonance Imaging
  • Middle Aged
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / pathology
  • Retrospective Studies
  • Steroid 17-alpha-Hydroxylase / metabolism*

Substances

  • inhibin-alpha subunit
  • Estradiol
  • Inhibins
  • Follicle Stimulating Hormone
  • Aromatase
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase