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KRAS mutation and microsatellite instability in endometrial adenocarcinomas showing MELF-type myometrial invasion
  1. C J R Stewart1,
  2. B Amanuel2,
  3. F Grieu2,
  4. A Carrello2,
  5. B Iacopetta3
  1. 1Department of Histopathology, King Edward Memorial Hospital, Subiaco, Australia
  2. 2Molecular Pathology, PathWest, Sir Charles Gairdner Hospital, Nedlands, Australia
  3. 3School of Surgery, University of Western Australia, Nedlands, Australia
  1. Correspondence to Dr C J R Stewart, Department of Histopathology, King Edward Memorial Hospital, Perth 6008, Western Australia, Australia; colin.stewart{at}health.wa.gov.au

Abstract

Background Some uterine endometrioid adenocarcinomas exhibit a distinctive morphological phenotype characterised by the formation of microcystic, elongated and fragmented (MELF) glands. Immunohistochemical studies have suggested that MELF-type changes represent an epithelial–mesenchymal transition which has been associated with KRAS activation in various tumours.

Aims To investigate the molecular characteristics of endometrial tumours showing MELF, with particular reference to the frequencies of KRAS and BRAF mutations and of microsatellite instability (MSI).

Methods MSI, and KRAS and BRAF mutation status, were assessed in 33 low-grade endometrial adenocarcinomas showing MELF features and the results compared with 33 control cases exhibiting a ‘conventional’ pattern of myometrial invasion. Standard histological parameters were also reviewed.

Results Tumours with a MELF pattern of myometrial invasion showed more frequent vascular invasion and focal mucinous differentiation. KRAS mutations were more frequent in MELF positive than MELF negative tumours (45% vs 30%), but this difference was not statistically significant. BRAF mutations were not identified in any of the cases. MSI was identified in 20% of cases overall but did not correlate with the MELF phenotype.

Conclusions Mutations in KRAS and BRAF genes are not directly implicated in the development of a MELF pattern of invasion in endometrial carcinoma. However, RAS-associated signalling pathways could be activated through other genetic or epigenetic mechanisms. The characterisation of such alterations may become increasingly important as novel therapies are developed that target mediators involved in tumour invasion.

  • Endometrial
  • carcinoma
  • MELF
  • KRAS
  • invasion
  • gynaecological pathology
  • histopathology
  • immunohistochemistry
  • molecular pathology

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Footnotes

  • Competing interests None.

  • Ethics approval Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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