J Clin Pathol 65:122-128 doi:10.1136/jclinpath-2011-200358
  • Original article

Loss of RKIP expression during the carcinogenic evolution of endometrial cancer

  1. Rui Manuel Reis1,2,5
  1. 1Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal
  2. 2ICVS/3B's—PT Government Associate Laboratory, Braga/Guimarães, Portugal
  3. 3Department of Gynecologic Oncology, A. C. Camargo Hospital, São Paulo, Brazil
  4. 4Department of Pathology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
  5. 5Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
  6. 6Laboratory of Medical Investigation (LIM) 14, Faculty of Medicine, São Paulo State University, São Paulo, Brazil
  7. 7Department of Pathology, A. C. Camargo Hospital, São Paulo, Brazil
  8. 8Department of Gynecologic Oncology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
  1. Correspondence to Dr Rui Manuel Reis, Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Villela, 1331, CEP 14784 400, Barretos, S. Paulo, Brazil; ruireis.hcb{at}
  1. Contributors OM performed the immunohistochemical reactions and drafted the manuscript. CCF, IWC and FAS constructed the tissue microarray. CSN and ALF evaluated the immunohistochemistry reactions. CCF, GB, IWC, FAS and JHTGF were involved in collection of clinical–pathological data and collaborated on the data interpretation. JHTGF and RMR were involved in the study concept and design, study supervision, statistical analysis and critical revision of the manuscript. All the authors have read and approved the final manuscript.

  • Accepted 1 September 2011
  • Published Online First 26 October 2011


Aims Endometrial cancer is one of the most common cancers in women worldwide, but there is a lack of diagnostic markers for early detection of these tumours. The raf kinase inhibitory protein (RKIP) negatively regulates the Raf/MEK/ERK pathway, and the downregulation of RKIP is associated with tumour progression and metastasis in several human neoplasms. The aim of this study was to assess the expression levels of RKIP in endometrial cancer and determine whether this expression correlates with clinical outcome in these patients.

Methods Tissue microarrays constructed using tissue samples from 209 endometrial adenocarcinomas, 49 endometrial polyps and 48 endometrial hyperplasias were analysed for RKIP expression by immunohistochemistry.

Results The authors found that RKIP expression decreases significantly during malignant progression of endometrial cancer; it is highly expressed in non-neoplastic tissues (polyps 79.6%; hyperplasias 87.5%) and expressed at very low levels in endometrioid adenocarcinomas (29.7%). No correlations were observed between RKIP expression, clinicopathological data and survival.

Conclusion This study demonstrated for the first time that RKIP expression is lost during the carcinogenic evolution of endometrial tumours and that the loss of RKIP expression is associated with a malignant phenotype. Functional studies are needed to address the biological role of RKIP downregulation in endometrial cancer.


  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was carried out with the approval of the local Institutional Review Board.

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