K-ras Mutations Common in Tamoxifen-Related Endometrial Polyps


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      K-ras Mutations Common in Tamoxifen-Related Endometrial Polyps


      Reuters Health Information 2003. © 2003 Reuters Ltd. 
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      By Will Boggs, MD
      NEW YORK (Reuters Health) Nov 19 - Tamoxifen may influence the development 
      of endometrial cancer by causing mutations in the K-ras gene, according to 
      a report in the November 1st issue of Cancer.
      Postmenopausal breast cancer patients treated with tamoxifen face an 
      increased risk of endometrial carcinoma, the authors explain, but it is 
      not known whether these tumors result from tamoxifen adducts to DNA or 
      because of the estrogenic nature or both.
      Because K-ras mutations are thought to occur at an early stage of 
      endometrial oncogenesis, Dr. Toru Hachisuga and colleagues from Fukuoka 
      University, Japan sought mutations in K-ras in 11 frozen endometrial 
      polyps from tamoxifen-treated patients with breast cancer.
      Seven of the 11 tamoxifen-related endometrial polyps contained mutations 
      in codon 12 of K-ras, the authors report. All of the mutations were in the 
      second base of codon 12.
      "Among the observed mutations in codon 12 of K-ras, four were identified 
      as GGT to GAT mutations and two were identified as GGT to GCT mutations," 
      the researchers note. "In contrast, in previous studies, GGT to GTT was 
      found to be the most common mutation in sporadic endometrial 
hyperplasias."
      Immunohistochemical findings included high expression levels of estrogen 
      receptor-alpha in the glandular epithelium and progesterone receptor-A in 
      both the glandular epithelium and the stroma, whereas estrogen 
      receptor-beta was expressed at lower levels and progesterone receptor-B 
      expression was high in the glandular epithelium and low in the stroma.
      "These histochemical findings were consistent with the findings for 
      hormone receptors in glandular epithelium in the proliferative phase," the 
      investigators explain.
      Dr. Hachisuga told Reuters Health that the team suspects that endometrial 
      cancer might be initiated from cooperation with mutagenic activity of 
      tamoxifen-DNA adducts and the estrogenic effect of tamoxifen. K-ras 
      mutation may be one manifestation of the pathway of carcinogenesis of 
      tamoxifen-related endometrium, he said.
      Dr. Hachisuga cautioned that the study was small, and said that the next 
      step is to examine K-ras mutations in larger numbers of tamoxifen-related 
      endometriums.
      Cancer 2003;09:1890-1897.


