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Loss of heterozygosity alterations associated with progesterone therapy in endometrial hyperplasia and adenocarcinoma
  1. M. Yasuda*,
  2. S. Kotajima*,
  3. H. Kajiwara*,
  4. S. Takekoshi*,
  5. R. Y. Osamura*,
  6. T. Yoshitake,
  7. T. Muramatsu,
  8. T. Miyamoto,
  9. M. Murakami and
  10. T. Shinozuka
  1. * Department of Pathology and Gynecology, School of Medicine, Tokai University, Isehara, Kanagawa, Japan
  2. Department of Obstetrics and Gynecology, School of Medicine, Tokai University, Isehara, Kanagawa, Japan
  1. Address correspondence and reprint requests to: Masanori Yasuda, MD, Department of Pathology, School of Medicine, Tokai University, Bohseidai, Isehara, Kanagawa, Japan. Email: m-yasuda{at}is.icc.u-tokai.ac.jp

Abstract

Loss of heterozygosity (LOH) was analyzed in four patients with endometrial hyperplasia (EH) with atypia (two patients) and without atypia (two patients) and in five patients with endometrial adenocarcinoma (EAC) to clarify the clinicopathologic relationship between genetic alterations and hormone therapy. Each patient was initially administered high-dose medroxyprogesterone acetate (MPA) as a uterine-sparing treatment. The five microsatellite markers used to analyze LOH were at chromosomal loci 8p22.1, 8p21, 8p21.3, 8p22, and 8p22. DNA was extracted from paraffin-embedded sections before, during, and after MPA therapy using laser capture microdissection. As a result, LOH was more frequently detected after MPA therapy (overall ratios were 16, 17, and 29% before, during, and after MPA therapy, respectively). LOH is more easily detected in EH loci than in EAC loci before MPA. For EAC, initial LOH detection on chromosome 8 may be related to an incomplete response to MPA, but negative LOH does not guarantee a favorable treatment outcome. For EH or atypical endometrial hyperplasia, it is unknown whether LOH alteration associated with MPA therapy is related to atypia of the disease.

  • endometrial hyperplasia and adenocarcinoma
  • loss of heterozygosity
  • medroxy progesterone acetate

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