Recurrence patterns and prognosis of endometrial stromal sarcoma and the potential of tyrosine kinase-inhibiting therapy

Gynecol Oncol. 2011 May 1;121(2):323-7. doi: 10.1016/j.ygyno.2010.12.360. Epub 2011 Jan 28.

Abstract

Objective: Endometrial stromal sarcoma (ESS) is a rare uterine malignancy. The current treatment approaches yield unsatisfactory results, and potential therapeutic targets need exploration.

Methods: We reviewed the electronic medical records of 74 patients with low-grade ESS who had been evaluated at the University of Texas MD Anderson Cancer Center between 1995 and 2006. Using immunohistochemistry, we tested the expression of targets in paraffin-embedded tissue samples taken from 13 of the patients.

Results: Forty-seven patients (64%) had a recurrence, and 16 (22%) had died of their disease at last follow-up. The 10-year progression-free survival (PFS) rate was 43% (median PFS duration, 108months), and the overall survival (OS) rate was 85% (median OS, 288months). Patients who received hormonal therapy had an overall response rate of 27%; another 53% had stable disease, with a median time to progression of 24months. No complete response or partial response was observed among patients who received radiotherapy or chemotherapy. In the paraffin-embedded specimens we tested, c-abl was expressed universally. Expression of PDGF-α, PDGF-β, VEGF, and c-Kit was detected in 33%, 36%, 54%, and 8%, of specimens, respectively. EGFR and HER-2 were not detectable in any specimens.

Conclusions: Our study suggests that ESS is a hormone-dependent malignancy, with hormonal therapy having activity in recurrent disease. Targeted therapy, specifically targeting c-abl may be a potential treatment for this disease.

MeSH terms

  • Adult
  • Aged
  • Disease-Free Survival
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / enzymology
  • Endometrial Neoplasms / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / enzymology
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / enzymology
  • Neoplasms, Hormone-Dependent / metabolism
  • Paraffin Embedding
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptors, Estrogen / biosynthesis
  • Receptors, Progesterone / biosynthesis
  • Retrospective Studies
  • Sarcoma, Endometrial Stromal / drug therapy*
  • Sarcoma, Endometrial Stromal / enzymology
  • Sarcoma, Endometrial Stromal / metabolism*
  • Young Adult

Substances

  • Protein Kinase Inhibitors
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor Protein-Tyrosine Kinases