Molecular profiling of endometrial carcinoma precursor, primary and metastatic lesions suggests different targets for treatment in obese compared to non-obese patients

Anna Berg, Erling A. Hoivik, Siv Mjøs, Frederik Holst, Henrica M.J. Werner, Ingvild L. Tangen, Amaro Taylor-Weiner, William J. Gibson, Kanthida Kusonmano, Elisabeth Wik, Jone Trovik, Mari K. Halle, Anne M. Øyan, Karl Henning Kalland, Andrew D. Cherniack, Rameen Beroukhim, Ingunn Stefansson, Gordon Mills, Camilla Krakstad, Helga B. Salvesen

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Obesity is linked to increased incidence of endometrioid endometrial cancer (EEC) and complex atypical hyperplasia (CAH). We here explore pattern and sequence of molecular alterations characterizing endometrial carcinogenesis in general and related to body mass index (BMI), to improve diagnostic stratification and treatment strategies. We performed molecular characterization of 729 prospectively collected EEC and CAH. Candidate biomarkers were identified in frozen samples by wholeexome and Sanger sequencing, oligonucleotide gene expression and Reverse Phase Protein Arrays (investigation cohort) and further explored in formalin fixed tissues by immunohistochemistry and Fluorescent in Situ Hybridization (validation cohort). We here demonstrate that PIK3CA mutations, PTEN loss, PI3K and KRAS activation are early events in endometrial carcinogenesis. Molecular changes related to KRAS activation and inflammation are more common in obese CAH patients, suggesting different prevention and systemic treatment strategies in obese and non-obese patients. We also found that oncoprotein Stathmin might improve preoperative diagnostic distinction between premalignant and malignant endometrial lesions.

Original languageEnglish (US)
Pages (from-to)1327-1339
Number of pages13
JournalOncotarget
Volume6
Issue number2
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Endometrial Neoplasms
Hyperplasia
Carcinogenesis
Stathmin
Protein Array Analysis
Oncogene Proteins
Fluorescence In Situ Hybridization
Phosphatidylinositol 3-Kinases
Oligonucleotides
Formaldehyde
Body Mass Index
Therapeutics
Obesity
Biomarkers
Immunohistochemistry
Inflammation
Gene Expression
Mutation
Incidence

Keywords

  • Body mass index
  • Endometrial carcinoma
  • Endometrial hyperplasia
  • Metastasis
  • PI3Kinase

ASJC Scopus subject areas

  • Oncology

Cite this

Molecular profiling of endometrial carcinoma precursor, primary and metastatic lesions suggests different targets for treatment in obese compared to non-obese patients. / Berg, Anna; Hoivik, Erling A.; Mjøs, Siv; Holst, Frederik; Werner, Henrica M.J.; Tangen, Ingvild L.; Taylor-Weiner, Amaro; Gibson, William J.; Kusonmano, Kanthida; Wik, Elisabeth; Trovik, Jone; Halle, Mari K.; Øyan, Anne M.; Kalland, Karl Henning; Cherniack, Andrew D.; Beroukhim, Rameen; Stefansson, Ingunn; Mills, Gordon; Krakstad, Camilla; Salvesen, Helga B.

In: Oncotarget, Vol. 6, No. 2, 01.01.2015, p. 1327-1339.

Research output: Contribution to journalArticle

Berg, A, Hoivik, EA, Mjøs, S, Holst, F, Werner, HMJ, Tangen, IL, Taylor-Weiner, A, Gibson, WJ, Kusonmano, K, Wik, E, Trovik, J, Halle, MK, Øyan, AM, Kalland, KH, Cherniack, AD, Beroukhim, R, Stefansson, I, Mills, G, Krakstad, C & Salvesen, HB 2015, 'Molecular profiling of endometrial carcinoma precursor, primary and metastatic lesions suggests different targets for treatment in obese compared to non-obese patients', Oncotarget, vol. 6, no. 2, pp. 1327-1339. https://doi.org/10.18632/oncotarget.2675
Berg, Anna ; Hoivik, Erling A. ; Mjøs, Siv ; Holst, Frederik ; Werner, Henrica M.J. ; Tangen, Ingvild L. ; Taylor-Weiner, Amaro ; Gibson, William J. ; Kusonmano, Kanthida ; Wik, Elisabeth ; Trovik, Jone ; Halle, Mari K. ; Øyan, Anne M. ; Kalland, Karl Henning ; Cherniack, Andrew D. ; Beroukhim, Rameen ; Stefansson, Ingunn ; Mills, Gordon ; Krakstad, Camilla ; Salvesen, Helga B. / Molecular profiling of endometrial carcinoma precursor, primary and metastatic lesions suggests different targets for treatment in obese compared to non-obese patients. In: Oncotarget. 2015 ; Vol. 6, No. 2. pp. 1327-1339.
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