Bergen forskningsgruppe for gynekologisk kreft

Dette prosjektet fokuserer på verdien av preoperativ avansert funksjonell bildebehandling for å gi funksjonelle og morfologiske svulstkarakteristikker som er relevante for behandling og prognose i endometriekreft. En unik pasientserie som prospektivt blir utsatt for preoperativ funksjonell bildebehandling ved magnetisk resonans imaging (MRI) og positronutslipp tomografi (PET) - computertomografi (CT) i løpet av 2009-2016, vil bli studert. Parallelt vil preklinisk PET-CT utført sekvensielt av en ortotopisk livmorkreft-musemodell bli undersøkt i forløpet av tumorprogresjon og metastase. Funksjonelle bildefunn i pasientene og dyremodellen vil bli utforsket i forhold til kirurgiske staging-resultater, utfall og histologiske og molekylære markører. Prosjektet tar sikte på å 1) Utforske funksjonelle bildefunn, dvs. potensielle bildebehandlingsbiomarkører som predikerer avansert tumorstadium, metastaser og redusert overlevelse i livmorhalskreft. 2) Validere og sammenligne disse billeddannende biomarkørene med etablerte histomorfologiske og molekylære biomarkører i livmorkreft og til slutt; 3) Implementere disse billeddannende biomarkørene i preoperativ risikostratifisering, for å muliggjøre bedre skreddersydd og individualisert behandling av livmorhalskreft.

Dette prosjektet er i samarbeid med Prof Ingfrid S Haldorsen. https://www.uib.no/en/rg/abdimaging

Endometriet er svært hormonfølsomt og uttrykker både østrogen og progesteronreseptorer. I endometriet hemmer progesteron den vekstfremmende effekten av østrogen, og induserer differensiering. Pasienter med høyt plasmaøstrogen og / eller lavt progesteron har økt risiko for endometriecancer, da østrogenets vekstfremmende effekt ikke balanseres av progesterondrevet differensiering. Flere studier har vist at ER og PR-status er viktige prognostiske biomarkører, og predikerer også respons på antihormonell behandling i endometriekreft. Vi har nylig identifisert at også AR har prognostisk innvirkning, og kan potensielt være et attraktivt terapeutisk mål. I dette prosjektet undersøker vi potensialet for faktorer relatert til hormonsignalering, som biomarkører i endometriekreft, og relaterer ekspresjon av disse markørene med klinisk fenotype og endringer i genuttrykk. Vi undersøker også endringer i uttrykk for disse markørene fra primære til metastatiske lesjoner. Det er ingen godkjente målrettede behandlinger, utover hormonell behandling for pasienter med endometriekreft. Derfor er karakterisering av metastasiske lesjoner, identifisering av nye biomarkører og potensielle terapeutiske mål både i primære og metastatiske lesjoner viktig for å forbedre behandlingen for disse pasientene.

Behandling av metastasert kreft er en stor utfordring i kreftbehandling. I denne studien fokuserer vi på endometriekreft, den vanligste gynekologiske krefttypen i Norge og den vestlige delen av verden. Vi har som mål å beskrive genetiske endringer, og å sammenligne den primære svulsten med metastaser hos kvinner med sykdomspredning. Dette ved hjelp av neste generasjons sekvenseringsverktøy (exome-sekvensering). En oppsiktsvekkende heterogenitet ble observert mellom biopsier av parede primære svulster og metastaser fra samme pasient, hvor bare halvparten av mutasjonene er felles i to biopsier -i gjennomsnitt. Når man definerer paret av mutasjoner i hver biopsi, kan et slektstre av den evolusjonære historien til endometriekreft avsløre informasjon om hvordan metastaser utvikler seg. Den nåværende modellen antyder at metastaserende endometriekreft stammer fra én enkelt grunnleggende subpopulasjon av primærtumoren. Denne studien utføres i nært samarbeid med ekspertforskere ved Broad Institute, Boston, USA.

Mer informasjon: The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis, Nature Genetics (2016). DOI: 10.1038/ng.3602

De overordnede målene med denne studien er å identifisere molekylære endringer som kan vise veien til nye behandlingsstrategier i livmorhalskreft, samt å avsløre potensielle biaser introdusert i prosessen med å avdekke molekylære endringer ved molekylærprofileringsteknikker som krever høyt tumorcelleinnhold.

Prosjektet har som mål å identifisere kandidatproteinmarkører (for eksempel HER2, p53) og å evaluere deres potensial som prognostiske og / eller prediktive markører som styrer behandling av livmorkreft. Ekspresjonen av kandidatmarkører er knyttet til kliniske trekk og transkripsjonsprofiler både i endometrie- og livmorkreft. I tillegg sammenlignes proteinekspresjonssmønstre i primære og samsvarende metastaserende endometriekreft-lesjoner.

Vi har etablert musemodeller for endometriekreft, hvor kreftceller er implantert i livmoren hos kvinnelige mus og som dermed vil danne tumor. I tillegg til bruk av kommersielt tilgjengelige kreftcellelinjer, implanterer vi også celler fra pasientenes primære svulster for å lage pasientledede xenografter (PDX), som antas å være mer representative for den kliniske fremstillingen enn cellelinjebaserte modeller. Musemodeller er verdifulle verktøy i preklinisk forskning, og kan brukes til å studere svulsters egenskaper og terapeutiske responser. Vi bruker vår endometriekreft-musemodell for å undersøke mulige forbindelser mellom ekspresjon av spesifikke proteiner i tumorceller og respons på utvalgte kjemoterapeutiske legemidler. Tumorvekst hos mus kan overvåkes over tid med forskjellige små dyrebildningsmodaliteter, og vi bruker for tiden PET-CT og optiske avbildningsteknikker for å visualisere tumorutvikling. Vi arbeider også med å etablere nye bildebehandlings-protokoller som kan brukes i PDX-modeller.

• Hjelmeland ME, Lien HE, Berg HF, Woie K, Werner HMJ, Amant F, Haldorsen IS, Trovik J, Krakstad C.
  Loss of vimentin expression in preoperative biopsies independently predicts poor prognosis, lymph node metastasis and recurrence in endometrial cancer.
  BJC Rep. 2024 Oct 18;2(1):81. doi: 10.1038/s44276-024-00105-2. PMID: 39516342; PMCID: PMC11524127.
   
• Krakstad C, Berg HF, Lindemann K, Halle MK.
  Frequency of ERBB2-Low Expression in Endometrial Cancer.
  JAMA Oncol. 2024 Nov 1;10(11):1587-1588. doi: 10.1001/jamaoncol.2024.3660. PMID: 39235791; PMCID: PMC11378060.
   
• Hodneland E, Andersen E, Wagner-Larsen KS, Dybvik JA, Lura N, Fasmer KE, Halle MK, Krakstad C, Haldorsen I.
  Impact of MRI radiomic feature normalization for prognostic modelling in uterine endometrial and cervical cancers.
  Sci Rep. 2024 Jul 22;14(1):16826. doi: 10.1038/s41598-024-66659-w. PMID: 39039099; PMCID: PMC11263557.
   
• van den Berg MC, Berg HF, Stokowy T, Hoivik EA, Woie K, Engerud H, Ojesina AI, Haldorsen IS, Trovik J, Bertelsen BI, Krakstad C, Halle MK.
  Expression patterns of mismatch repair proteins in cervical cancer uncover independent prognostic value of MSH-2.
  Int J Gynecol Cancer. 2024 Jul 1;34(7):993-1000. doi: 10.1136/ijgc-2024-005377. PMID: 38950928; PMCID: PMC11228214.
   
• Luijten MMW, van Weelden WJ, Lalisang RI, Bulten J, Lindemann K, van Beekhuizen HJ, Trum H, Boll D, Werner HMJ, van Lonkhuijzen LRCW, Yigit R, Krakstad C, Witteveen PO, Galaal K, van Ginkel AA, Bignotti E, Weinberger V, Sweegers S, Eriksson AGZ, Keizer DM, van de Stolpe A, Romano A, Pijnenborg JMA, European Network For Individualized Treatment In Endometrial Cancer.
  Hormone Receptor Expression and Activity for Different Tumour Locations in Patients with Advanced and Recurrent Endometrial Carcinoma. Cancers (Basel).
  2024 May 30;16(11):2084. doi: 10.3390/cancers16112084. PMID: 38893205; PMCID: PMC11171125.
   
• Espedal H, Fasmer KE, Berg HF, Lyngstad JM, Schilling T, Krakstad C, Haldorsen IS.
  MRI radiomics captures early treatment response in patient-derived organoid endometrial cancer mouse models.
  Front Oncol. 2024 May 7;14:1334541. doi: 10.3389/fonc.2024.1334541. PMID: 38774411; PMCID: PMC11106402.
   
• Halle MK, Hodneland E, Wagner-Larsen KS, Lura NG, Fasmer KE, Berg HF, Stokowy T, Srivastava A, Forsse D, Hoivik EA, Woie K, Bertelsen BI, Krakstad C, Haldorsen IS.
  Radiomic profiles improve prognostication and reveal targets for therapy in cervical cancer.
  Sci Rep. 2024 May 17;14(1):11339. doi: 10.1038/s41598-024-61271-4. PMID: 38760387; PMCID: PMC11101482.
   
• Bellone S, Jeong K, Halle MK, Krakstad C, McNamara B, Greenman M, Mutlu L, Demirkiran C, Hartwich TMP, Yang-Hartwich Y, Zipponi M, Buza N, Hui P, Raspagliesi F, Lopez S, Paolini B, Milione M, Perrone E, Scambia G, Altwerger G, Ravaggi A, Bignotti E, Huang GS, Andikyan V, Clark M, Ratner E, Azodi M, Schwartz PE, Quick CM, Angioli R, Terranova C, Zaidi S, Nandi S, Alexandrov LB, Siegel ER, Choi J, Schlessinger J, Santin AD.
  Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix.
  Proc Natl Acad Sci U S A. 2024 Apr 23;121(17):e2321898121. doi: 10.1073/pnas.2321898121. Epub 2024 Apr 16. PMID: 38625939; PMCID: PMC11046577.

2023

• Halle MK, Bozickovic O, Forsse D, Wagner-Larsen KS, Gold RM, Lura NG, Woie K, Bertelsen BI, Haldorsen IS, Krakstad C.
  Clinicopathological and radiological stratification within FIGO 2018 stages improves risk-prediction in cervical cancer.
  Gynecol Oncol. 2023 Dec 26;181:110-117. doi: 10.1016/j.ygyno.2023.12.014. PMID: 38150835
   
• Wagner-Larsen KS, Hodneland E, Fasmer KE, Lura N, Woie K, Bertelsen BI, Salvesen Ø, Halle MK, Smit N, Krakstad C, Haldorsen IS.
  MRI-based radiomic signatures for pretreatment prognostication in cervical cancer.
  Cancer Med. 2023 Oct;12(20):20251-20265. doi: 10.1002/cam4.6526. Epub 2023 Oct 16. PMID: 37840437.
   
• Eide AJ, Halle MK, Lura N, Fasmer KE, Wagner-Larsen K, Forsse D, Bertelsen BI, Salvesen Ø, Krakstad C, Haldorsen IS.
  Visceral fat percentage for prediction of outcome in uterine cervical cancer.
  Gynecol Oncol. 2023 Sep;176:62-68. doi: 10.1016/j.ygyno.2023.06.581. Epub 2023 Jul 13. PMID: 37453220.
   
• Torkildsen CF, Thomsen LCV, Sande RK, Krakstad C, Stefansson I, Lamark EK, Knappskog S, Bjørge L.
  Molecular and phenotypic characteristics influencing the degree of cytoreduction in high-grade serous ovarian carcinomas.
  Cancer Med. 2023 Jul;12(13):14183-14195. doi: 10.1002/cam4.6085. Epub 2023 May 16. PMID: 37191035; PMCID: PMC10358208.
   
• Lien HE, Berg HF, Halle MK, Trovik J, Haldorsen IS, Akslen LA, Krakstad C.
  Single-cell profiling of low-stage endometrial cancers identifies low epithelial vimentin expression as a marker of recurrent disease.
  EBioMedicine. 2023 Jun;92:104595. doi: 10.1016/j.ebiom.2023.104595. Epub 2023 May 3. PMID: 37146405; PMCID: PMC10277918.
   
• Lombaers MS, Cornel KMC, Visser NCM, Bulten J, Küsters-Vandevelde HVN, Amant F, Boll D, Bronsert P, Colas E, Geomini PMAJ, Gil-Moreno A, van Hamont D, Huvila J, Krakstad C, Kraayenbrink AA, Koskas M, Mancebo G, Matías-Guiu X, Ngo H, Pijlman BM, Vos MC, Weinberger V, Snijders MPLM, van Koeverden SW, Enitec-Consortium, Haldorsen IS, Reijnen C, Pijnenborg JMA.
  Preoperative CA125 Significantly Improves Risk Stratification in High-Grade Endometrial Cancer.
  Cancers (Basel). 2023 May 4;15(9):2605. doi: 10.3390/cancers15092605. PMID: 37174070; PMCID: PMC10177432.
   
• Bredin HK, Krakstad C, Hoivik EA.
  PIK3CA mutations and their impact on survival outcomes of patients with endometrial cancer: A systematic review and meta-analysis.
  PLoS One. 2023 Mar 21;18(3):e0283203. doi: 10.1371/journal.pone.0283203. PMID: 36943861; PMCID: PMC10030019.
   
• Sofiyeva N, Krakstad C, Halle MK, O'Mara TA, Romundstad P, Hveem K, Vatten L, Lønning PE, Gansmo LB, Knappskog S.
  APOBEC3A/B deletion polymorphism and endometrial cancer risk.
  Cancer Med. 2023 Mar;12(6):6659-6667. doi: 10.1002/cam4.5448. Epub 2022 Nov 16. PMID: 36394079; PMCID: PMC10067079.
   
• Berg HF, Engerud H, Myrvold M, Lien HE, Hjelmeland ME, Halle MK, Woie K, Hoivik EA, Haldorsen IS, Vintermyr O, Trovik J, Krakstad C.
  Mismatch repair markers in preoperative and operative endometrial cancer samples; expression concordance and prognostic value.
  Br J Cancer. 2023 Feb;128(4):647-655. doi: 10.1038/s41416-022-02063-3. Epub 2022 Dec 8. PMID: 36482191; PMCID: PMC9938259.
   
• Fasmer KE, Gulati A, Dybvik JA, Wagner-Larsen KS, Lura N, Salvesen Ø, Forsse D, Trovik J, Pijnenborg JMA, Krakstad C, Haldorsen IS.
  Preoperative pelvic MRI and 2-[¹⁸F]FDG PET/CT for lymph node staging and prognostication in endometrial cancer-time to revisit current imaging guidelines?
  Eur Radiol. 2023 Jan;33(1):221-232. doi: 10.1007/s00330-022-08949-3. Epub 2022 Jun 28. PMID: 35763096; PMCID: PMC9755079.

2022

• Wagner-Larsen KS, Lura N, Salvesen Ø, Halle MK, Forsse D, Trovik J, Smit N, Krakstad C, Haldorsen IS. Interobserver agreement and prognostic impact for MRI-based 2018 FIGO staging parameters in uterine cervical cancer. Eur Radiol. 2022 Sep;32(9):6444-6455. doi: 10.1007/s00330-022-08666-x. Epub 2022 Mar 24. PMID: 35332408; PMCID: PMC9381622.

• Lura N, Wagner-Larsen KS, Forsse D, Trovik J, Halle MK, Bertelsen BI, Salvesen Ø, Woie K, Krakstad C, Haldorsen IS. What MRI-based tumor size measurement is best for predicting long-term survival in uterine cervical cancer? Insights Imaging. 2022 Jun 17;13(1):105. doi: 10.1186/s13244-022-01239-y. PMID: 35715582; PMCID: PMC9206052.

• Hodneland E, Kaliyugarasan S, Wagner-Larsen KS, Lura N, Andersen E, Bartsch H, Smit N, Halle MK, Krakstad C, Lundervold AS, Haldorsen IS. Fully Automatic Whole-Volume Tumor Segmentation in Cervical Cancer. Cancers (Basel). 2022 May 11;14(10):2372. doi: 10.3390/cancers14102372. PMID: 35625977; PMCID: PMC9139985.

• Dybvik JA, Fasmer KE, Ytre-Hauge S, Husby JHA, Salvesen ØO, Stefansson IM, Krakstad C, Trovik J, Haldorsen IS. MRI-assessed tumor-free distance to serosa predicts deep myometrial invasion and poor outcome in endometrial cancer. Insights Imaging. 2022 Jan 8;13(1):1. doi: 10.1186/s13244-021-01133-z. PMID: 35000020; PMCID: PMC8742796.

• Forsse D, Barbero ML, Werner HMJ, Woie K, Nordskar N, Berge Nilsen E, Ellstrøm Engh M, Vistad I, Rege A, Sævik-Lode M, Andreasen S, Haldorsen IS, Trovik J, Krakstad C. Longitudinal effects of adjuvant chemotherapy and lymph node staging on patient-reported outcomes in endometrial cancer survivors: a prospective cohort study. Am J Obstet Gynecol. 2022 Jan;226(1):90.e1-90.e20. doi: 10.1016/j.ajog.2021.08.011. Epub 2021 Aug 13. PMID: 34400137.

• Chakravarthy A, Reddin I, Henderson S, Dong C, Kirkwood N, Jeyakumar M, Rodriguez DR, Martinez NG, McDermott J, Su X, Egawa N, Fjeldbo CS, Skingen VE, Lyng H, Halle MK, Krakstad C, Soleiman A, Sprung S, Lechner M, Ellis PJI, Wass M, Michaelis M, Fiegl H, Salvesen H, Thomas GJ, Doorbar J, Chester K, Feber A, Fenton TR. Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance. Nat Commun. 2022 Oct 7;13(1):5818. doi: 10.1038/s41467-022-33544-x. PMID: 36207323; PMCID: PMC9547055.

2021

• Øvestad IT, Engesæter B, Halle MK, Akbari S, Bicskei B, Lapin M, Austdal M, Janssen EAM, Krakstad C, Lillesand M, Nordhus M, Munk AC, Gudlaugsson EG. High-Grade Cervical Intraepithelial Neoplasia (CIN) Associates with Increased Proliferation and Attenuated Immune Signaling. Int J Mol Sci. 2021 Dec 29;23(1):373. doi: 10.3390/ijms23010373. PMID: 35008799; PMCID: PMC8745058.

• Hoivik EA, Hodneland E, Dybvik JA, Wagner-Larsen KS, Fasmer KE, Berg HF, Halle MK, Haldorsen IS, Krakstad C. A radiogenomics application for prognostic profiling of endometrial cancer. Commun Biol. 2021 Dec 6;4(1):1363. doi: 10.1038/s42003-021-02894-5. PMID: 34873276; PMCID: PMC8648740.

• Kasius JC, Pijnenborg JMA, Lindemann K, Forsse D, van Zwol J, Kristensen GB, Krakstad C, Werner HMJ, Amant F. Risk Stratification of Endometrial Cancer Patients: FIGO Stage, Biomarkers and Molecular Classification. Cancers (Basel). 2021 Nov 22;13(22):5848. doi: 10.3390/cancers13225848. PMID: 34831000; PMCID: PMC8616052.

• Halle MK, Munk AC, Engesæter B, Akbari S, Frafjord A, Hoivik EA, Forsse D, Fasmer KE, Woie K, Haldorsen IS, Bertelsen BI, Janssen EAM, Gudslaugsson E, Krakstad C, Øvestad IT. A Gene Signature Identifying CIN3 Regression and Cervical Cancer Survival. Cancers (Basel). 2021 Nov 16;13(22):5737. doi: 10.3390/cancers13225737. PMID: 34830895; PMCID: PMC8616457.

• Halle MK, Sundaresan A, Zhang J, Pedamallu CS, Srinivasasainagendra V, Blair J, Brooke D, Bertelsen BI, Woie K, Shrestha S, Tiwari H, Wong YF, Krakstad C, Ojesina AI. Genomic alterations associated with mutational signatures, DNA damage repair and chromatin remodeling pathways in cervical carcinoma. NPJ Genom Med. 2021 Oct 7;6(1):82. doi: 10.1038/s41525-021-00244-2. PMID: 34620846; PMCID: PMC8497615.

• van Weelden WJ, Lalisang RI, Bulten J, Lindemann K, van Beekhuizen HJ, Trum H, Boll D, Werner HMJ, van Lonkhuijzen LRCW, Yigit R, Forsse D, Witteveen PO, Galaal K, van Ginkel A, Bignotti E, Weinberger V, Sweegers S, Kroep JR, Cabrera S, Snijders MPLM, Inda MA, Eriksson AGZ; European Network for Individualized Treatment in Endometrial Cancer; Krakstad C, Romano A, van de Stolpe A, Pijnenborg JMA. Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial cancer. Am J Obstet Gynecol. 2021 Oct;225(4):407.e1-407.e16. doi: 10.1016/j.ajog.2021.05.007. Epub 2021 May 19. PMID: 34019887.

• Espedal H, Berg HF, Fonnes T, Fasmer KE, Krakstad C, Haldorsen IS. Feasibility and utility of MRI and dynamic ¹⁸F-FDG-PET in an orthotopic organoid-based patient-derived mouse model of endometrial cancer. J Transl Med. 2021 Sep 26;19(1):406. doi: 10.1186/s12967-021-03086-9. PMID: 34565386; PMCID: PMC8474962.

• Ruiz FJ, Sundaresan A, Zhang J, Pedamallu CS, Halle MK, Srinivasasainagendra V, Zhang J, Muhammad N, Stanley J, Markovina S, Tiwari HK, Grigsby PW, Krakstad C, Schwarz JK, Ojesina AI. Genomic Characterization and Therapeutic Targeting of HPV Undetected Cervical Carcinomas. Cancers (Basel). 2021 Sep 10;13(18):4551. doi: 10.3390/cancers13184551. PMID: 34572780; PMCID: PMC8467954.

• Berg HF, Hjelmeland ME, Lien H, Espedal H, Fonnes T, Srivastava A, Stokowy T, Strand E, Bozickovic O, Stefansson IM, Bjørge L, Trovik J, Haldorsen IS, Hoivik EA, Krakstad C. Patient-derived organoids reflect the genetic profile of endometrial tumors and predict patient prognosis. Commun Med (Lond). 2021 Jul 30;1:20. doi: 10.1038/s43856-021-00019-x. Erratum in: Commun Med (Lond). 2021 Aug 10;1:22. PMID: 35602206; PMCID: PMC9053236.

• Amant F, McCluggage WG, Werner HMJ, Kasius JC, Krakstad C, Pijnenborg J. Incorporating molecular profiling into endometrial cancer management requires prospective studies. Int J Gynecol Cancer. 2021 Jun;31(6):944-945. doi: 10.1136/ijgc-2021-002705. Epub 2021 May 7. PMID: 33962995.

• Vrede SW, van Weelden WJ, Visser NCM, Bulten J, van der Putten LJM, van de Vijver K, Santacana M, Colas E, Gil-Moreno A, Moiola CP, Mancebo G, Krakstad C, Trovik J, Haldorsen IS, Huvila J, Koskas M, Weinberger V, Bednarikova M, Hausnerova J, van der Wurff AA, Matias-Guiu X, Amant F; ENITEC Consortium; Snijders MPLM, Küsters-Vandevelde HVN, Reijnen C, Pijnenborg JMA. Immunohistochemical biomarkers are prognostic relevant in addition to the ESMO-ESGO-ESTRO risk classification in endometrial cancer. Gynecol Oncol. 2021 Jun;161(3):787-794. doi: 10.1016/j.ygyno.2021.03.031. Epub 2021 Apr 12. PMID: 33858677.

• Helwa R, Gansmo LB, Bjørnslett M, Halle MK, Werner HMJ, Romundstad P, Hveem K, Vatten L, Dørum A, Lønning PE, Knappskog S. Impact of MDM2 promoter SNP55 (rs2870820) on risk of endometrial and ovarian cancer. Biomarkers. 2021 Jun;26(4):302-308. doi: 10.1080/1354750X.2021.1891291. Epub 2021 Feb 28. PMID: 33645339.

• Halle MK, Sødal M, Forsse D, Engerud H, Woie K, Lura NG, Wagner-Larsen KS, Trovik J, Bertelsen BI, Haldorsen IS, Ojesina AI, Krakstad C. A 10-gene prognostic signature points to LIMCH1 and HLA-DQB1 as important players in aggressive cervical cancer disease. Br J Cancer. 2021 May;124(10):1690-1698. doi: 10.1038/s41416-021-01305-0. Epub 2021 Mar 15. PMID: 33723390; PMCID: PMC8110544.

• Lindemann K, Smogeli E, Småstuen MC, Bruheim K, Trovik J, Nordberg T, Kristensen GB, Werner HMJ, Nakken E. Salvage Radiation for Pelvic Relapse after Surgically Treated Endometrial Cancer. Cancers (Basel). 2021 Mar 18;13(6):1367. doi: 10.3390/cancers13061367. PMID: 33803531; PMCID: PMC8002978.

• Fasmer KE, Hodneland E, Dybvik JA, Wagner-Larsen K, Trovik J, Salvesen Ø, Krakstad C, Haldorsen IHS. Whole-Volume Tumor MRI Radiomics for Prognostic Modeling in Endometrial Cancer. J Magn Reson Imaging. 2021 Mar;53(3):928-937. doi: 10.1002/jmri.27444. Epub 2020 Nov 16. PMID: 33200420; PMCID: PMC7894560.

• Jacob H, Dybvik JA, Ytre-Hauge S, Fasmer KE, Hoivik EA, Trovik J, Krakstad C, Haldorsen IS. An MRI-Based Radiomic Prognostic Index Predicts Poor Outcome and Specific Genetic Alterations in Endometrial Cancer. J Clin Med. 2021 Feb 2;10(3):538. doi: 10.3390/jcm10030538. PMID: 33540589; PMCID: PMC7867221.

• Forsse D, Berg HF, Bozickovic O, Engerud H, Halle MK, Hoivik EA, Woie K, Werner HMJ, Haldorsen IS, Trovik J, Krakstad C. Maintained survival outcome after reducing lymphadenectomy rates and optimizing adjuvant treatment in endometrial cancer. Gynecol Oncol. 2021 Feb;160(2):396-404. doi: 10.1016/j.ygyno.2020.12.002. Epub 2020 Dec 13. PMID: 33317908.

• Kho PF, Amant F, Annibali D, Ashton K, Attia J, Auer PL, Beckmann MW, Black A, Brinton L, Buchanan DD, Chanock SJ, Chen C, Chen MM, Cheng THT, Cook LS, Crous-Bous M, Czene K, De Vivo I, Dennis J, Dörk T, Dowdy SC, Dunning AM, Dürst M, Easton DF, Ekici AB, Fasching PA, Fridley BL, Friedenreich CM, García-Closas M, Gaudet MM, Giles GG, Goode EL, Gorman M, Haiman CA, Hall P, Hankinson SE, Hein A, Hillemanns P, Hodgson S, Hoivik EA, Holliday EG, Hunter DJ, Jones A, Kraft P, Krakstad C, Lambrechts D, Le Marchand L, Liang X, Lindblom A, Lissowska J, Long J, Lu L, Magliocco AM, Martin L, McEvoy M, Milne RL, Mints M, Nassir R, Otton G, Palles C, Pooler L, Proietto T, Rebbeck TR, Renner SP, Risch HA, Rübner M, Runnebaum I, Sacerdote C, Sarto GE, Schumacher F, Scott RJ, Setiawan VW, Shah M, Sheng X, Shu XO, Southey MC, Tham E, Tomlinson I, Trovik J, Turman C, Tyrer JP, Van Den Berg D, Wang Z, Wentzensen N, Xia L, Xiang YB, Yang HP, Yu H, Zheng W, Webb PM, Thompson DJ, Spurdle AB, Glubb DM, O'Mara TA. Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer. Int J Cancer. 2021 Jan 15;148(2):307-319. doi: 10.1002/ijc.33206. Epub 2020 Aug 7. PMID: 32851660; PMCID: PMC7757859.

• Hodneland E, Dybvik JA, Wagner-Larsen KS, Šoltészová V, Munthe-Kaas AZ, Fasmer KE, Krakstad C, Lundervold A, Lundervold AS, Salvesen Ø, Erickson BJ, Haldorsen I. Automated segmentation of endometrial cancer on MR images using deep learning. Sci Rep. 2021 Jan 8;11(1):179. doi: 10.1038/s41598-020-80068-9. PMID: 33420205; PMCID: PMC7794479.

• Fonnes T, Telle IO, Forsse D, Falck R, Trovik J, Haldorsen IS, Krakstad C. Cancer awareness in the general population varies with sex, age and media coverage: A population-based survey with focus on gynecologic cancers. Eur J Obstet Gynecol Reprod Biol. 2021 Jan;256:25-31. doi: 10.1016/j.ejogrb.2020.10.051. Epub 2020 Nov 1. PMID: 33161211.

2020

• Ytre-Hauge S, Salvesen ØO, Krakstad C, Trovik J, Haldorsen IS. Tumour texture features from preoperative CT predict high-risk disease in endometrial cancer. Clin Radiol. 2021 Jan;76(1):79.e13-79.e20. doi: 10.1016/j.crad.2020.07.037. Epub 2020 Sep 14. PMID: 32938538.

• Kleppe A, Albregtsen F, Trovik J, Kristensen GB, Danielsen HE. Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas. Cancers (Basel). 2020 Dec 19;12(12):3838. doi: 10.3390/cancers12123838. PMID: 33352679; PMCID: PMC7766595.

• Baxter E, Brennan DJ, McAlpine JN, Mueller JJ, Amant F, van Gent MDJM, Huntsman DG, Coleman RL, Westin SN, Yates MS, Krakstad C, Quinn MA, Janda M, Obermair A. Improving response to progestin treatment of low-grade endometrial cancer. Int J Gynecol Cancer. 2020 Nov;30(11):1811-1823. doi: 10.1136/ijgc-2020-001309. Epub 2020 May 6. Erratum in: Int J Gynecol Cancer. 2021 Oct;31(10):1401. PMID: 32381512; PMCID: PMC8445150.

• Obermair A, Baxter E, Brennan DJ, McAlpine JN, Muellerer JJ, Amant F, van Gent MDJM, Coleman RL, Westin SN, Yates MS, Krakstad C, Janda M. Fertility-sparing treatment in early endometrial cancer: current state and future strategies. Obstet Gynecol Sci. 2020 Jul;63(4):417-431. doi:  10.5468/ogs.19169. Epub 2020 Jul 8. PMID: 32689770; PMCID: PMC7393748.

• Reijnen C, Gogou E, Visser NCM, Engerud H, Ramjith J, van der Putten LJM, van de Vijver K, Santacana M, Bronsert P, Bulten J, Hirschfeld M, Colas E, Gil-Moreno A, Reques A, Mancebo G, Krakstad C, Trovik J, Haldorsen IS, Huvila J, Koskas M, Weinberger V, Bednarikova M, Hausnerova J, van der Wurff AAM, Matias-Guiu X, Amant F; ENITEC Consortium; Massuger LFAG, Snijders MPLM, Küsters-Vandevelde HVN, Lucas PJF, Pijnenborg JMA. Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study. PLoS Med. 2020 May 15;17(5):e1003111. doi: 10.1371/journal.pmed.1003111. PMID: 32413043; PMCID: PMC7228042.

• Fasmer KE, Gulati A, Dybvik JA, Ytre-Hauge S, Salvesen Ø, Trovik J, Krakstad C, Haldorsen IS. Preoperative 18F-FDG PET/CT tumor markers outperform MRI-based markers for the prediction of lymph node metastases in primary endometrial cancer. Eur Radiol. 2020 May;30(5):2443-2453. doi: 10.1007/s00330-019-06622-w. Epub 2020 Feb 7. PMID: 32034487; PMCID: PMC7160067.

• Engerud H, Berg HF, Myrvold M, Halle MK, Bjorge L, Haldorsen IS, Hoivik EA, Trovik J, Krakstad C. High degree of heterogeneity of PD-L1 and PD-1 from primary to metastatic endometrial cancer. Gynecol Oncol. 2020 Apr;157(1):260-267. doi: 10.1016/j.ygyno.2020.01.020. Epub 2020 Jan 21. PMID: 31973911.

• Berg HF, Ju Z, Myrvold M, Fasmer KE, Halle MK, Hoivik EA, Westin SN, Trovik J, Haldorsen IS, Mills GB, Krakstad C, Werner HMJ. Development of prediction models for lymph node metastasis in endometrioid endometrial carcinoma. Br J Cancer. 2020 Mar;122(7):1014-1022. doi: 10.1038/s41416-020-0745-6. Epub 2020 Feb 10. PMID: 32037399; PMCID: PMC7109044.

• Fonnes T, Strand E, Fasmer KE, Berg HF, Espedal H, Sortland K, Stefansson I, Bjørge L, Haldorsen IS, Krakstad C, McCormack E. Near-Infrared Fluorescent Imaging for Monitoring of Treatment Response in Endometrial Carcinoma Patient-Derived Xenograft Models. Cancers (Basel). 2020 Feb 6;12(2):370. doi: 10.3390/cancers12020370. PMID: 32041116; PMCID: PMC7072497.

• Forsse D, Tangen IL, Fasmer KE, Halle MK, Viste K, Almås B, Bertelsen BE, Trovik J, Haldorsen IS, Krakstad C. Blood steroid levels predict survival in endometrial cancer and reflect tumor estrogen signaling. Gynecol Oncol. 2020 Feb;156(2):400-406. doi: 10.1016/j.ygyno.2019.11.123. Epub 2019 Dec 6. PMID: 31813586.

2019

• Strand E, Tangen IL, Fasmer KE, Jacob H, Halle MK, Hoivik EA, Delvoux B, Trovik J, Haldorsen IS, Romano A, Krakstad C. Blood Metabolites Associate with Prognosis in Endometrial Cancer. Metabolites. 2019 Dec 14;9(12):302. doi: 10.3390/metabo9120302. PMID: 31847385; PMCID: PMC6949989.

• Espedal H, Fonnes T, Fasmer KE, Krakstad C, Haldorsen IS. Imaging of Preclinical Endometrial Cancer Models for Monitoring Tumor Progression and Response to Targeted Therapy. Cancers (Basel). 2019 Nov 27;11(12):1885. doi: 10.3390/cancers11121885. PMID: 31783595; PMCID: PMC6966645.

• Visser NCM, van der Putten LJM, van Egerschot A, Van de Vijver KK, Santacana M, Bronsert P, Hirschfeld M, Colas E, Gil-Moreno A, Garcia A, Mancebo G, Alameda F, Krakstad C, Tangen IL, Huvila J, Schrauwen S, Koskas M, Walker F, Weinberger V, Minar L, Hausnerova J, Snijders MPLM, van den Berg-van Erp S, Matias-Guiu X, Trovik J, Amant F, Massuger LFAG, Bulten J, Pijnenborg JMA. Addition of IMP3 to L1CAM for discrimination between low- and high-grade endometrial carcinomas: a European Network for Individualised Treatment of Endometrial Cancer collaboration study. Hum Pathol. 2019 Jul;89:90-98. doi: 10.1016/j.humpath.2019.04.014. Epub 2019 May 3. PMID: 31054899.

• van Weelden WJ, Fasmer KE, Tangen IL, IntHout J, Abbink K, van Herwaarden AE, Krakstad C, Massuger LFAG, Haldorsen IS, Pijnenborg JMA. Impact of body mass index and fat distribution on sex steroid levels in endometrial carcinoma: a retrospective study. BMC Cancer. 2019 Jun 7;19(1):547. doi: 10.1186/s12885-019-5770-6. PMID: 31174495; PMCID: PMC6555924.

• Reijnen C, van Weelden WJ, Arts MSJP, Peters JP, Rijken PF, van de Vijver K, Santacana M, Bronsert P, Bulten J, Hirschfeld M, Colas E, Gil-Moreno A, Reques A, Mancebo G, Krakstad C, Trovik J, Haldorsen IS, Huvila J, Koskas M, Weinberger V, Minar L, Jandakova E, Snijders MPLM, van den Berg-van Erp S, Küsters-Vandevelde HVN, Matias-Guiu X, Amant F; ENITEC-consortium; Massuger LFAG, Bussink J, Pijnenborg JMA. Poor outcome in hypoxic endometrial carcinoma is related to vascular density. Br J Cancer. 2019 May;120(11):1037-1044. doi: 10.1038/s41416-019-0461-2. Epub 2019 Apr 23. PMID: 31011231; PMCID: PMC6738053.

• Engerud H, Hope K, Berg HF, Fasmer KE, Tangen IL, Haldorsen IS, Trovik J, Krakstad C. Plasma growth differentiation factor-15 is an independent marker for aggressive disease in endometrial cancer. PLoS One. 2019 Jan 15;14(1):e0210585. doi: 10.1371/journal.pone.0210585. PMID: 30645608; PMCID: PMC6333370.

• Tangen IL, Fasmer KE, Konings GF, Jochems A, Delvoux B, Xanthoulea S, Stokowy T, Strand E, Berg HF, Auriola S, Trovik J, Häkkinen MR, Haldorsen IS; ENITEC. Electronic address: https://www.esgo.org; Krakstad C, Romano A. Blood steroids are associated with prognosis and fat distribution in endometrial cancer. Gynecol Oncol. 2019 Jan;152(1):46-52. doi: 10.1016/j.ygyno.2018.10.024. Epub 2018 Oct 26. PMID: 30554934.

2018

• Ytre-Hauge S, Esmaeili M, Sjøbakk TE, Grüner R, Woie K, Werner HM, Krakstad C, Bjørge L, Salvesen ØO, Stefansson IM, Trovik J, Bathen TF, Haldorsen IS. In vivo MR spectroscopy predicts high tumor grade in endometrial cancer. Acta Radiol. 2018 Apr;59(4):497-505. doi: 10.1177/0284185117733297. Epub 2017 Sep 19. PMID: 28927296.

• Ytre-Hauge S, Dybvik JA, Lundervold A, Salvesen ØO, Krakstad C, Fasmer KE, Werner HM, Ganeshan B, Høivik E, Bjørge L, Trovik J, Haldorsen IS. Preoperative tumor texture analysis on MRI predicts high-risk disease and reduced survival in endometrial cancer. J Magn Reson Imaging. 2018 Dec;48(6):1637-1647. doi: 10.1002/jmri.26184. Epub 2018 Aug 13. PMID: 30102441.

• Versluis M, Plat A, de Bruyn M, Matias-Guiu X, Trovic J, Krakstad C, Nijman HW, Bosse T, de Bock GH, Hollema H. L1CAM expression in uterine carcinosarcoma is limited to the epithelial component and may be involved in epithelial-mesenchymal transition. Virchows Arch. 2018 Nov;473(5):591-598. doi: 10.1007/s00428-018-2444-8. Epub 2018 Aug 23. PMID: 30140948.

• Painter JN, O'Mara TA, Morris AP, Cheng THT, Gorman M, et al.. Patient-Derived Xenograft Models for Endometrial Cancer Research. Int J Mol Sci. 2018 Aug 17;19(8):2431. doi: 10.3390/ijms19082431. PMID: 30126113; PMCID: PMC6121639.

• Mazloumi Gavgani F, Smith Arnesen V, Jacobsen RG, Krakstad C, Hoivik EA, Lewis AE. Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer. Int J Mol Sci. 2018 Dec 7;19(12):3931. doi: 10.3390/ijms19123931. PMID: 30544563; PMCID: PMC6321576.

• Kusonmano K, Halle MK, Wik E, Hoivik EA, Krakstad C, Mauland KK, Tangen IL, Berg A, Werner HMJ, Trovik J, Øyan AM, Kalland KH, Jonassen I, Salvesen HB, Petersen K. Identification of highly connected and differentially expressed gene subnetworks in metastasizing endometrial cancer. PLoS One. 2018 Nov 1;13(11):e0206665. doi: 10.1371/journal.pone.0206665. PMID: 30383835; PMCID: PMC6211718.

• Konings GF, Cornel KM, Xanthoulea S, Delvoux B, Skowron MA, Kooreman L, Koskimies P, Krakstad C, Salvesen HB, van Kuijk K, Schrooders YJ, Vooijs M, Groot AJ, Bongers MY, Kruitwagen RF; ENITEC; Romano A. Blocking 17β-hydroxysteroid dehydrogenase type 1 in endometrial cancer: a potential novel endocrine therapeutic approach. J Pathol. 2018 Feb;244(2):203-214. doi: 10.1002/path.5004. Epub 2018 Jan 3. PMID: 29144553.

• Konings GF, Saarinen N, Delvoux B, Kooreman L, Koskimies P, Krakstad C, Fasmer KE, Haldorsen IS, Zaffagnini A, Häkkinen MR, Auriola S, Dubois L, Lieuwes N, Verhaegen F, Schyns LE, Kruitwagen RF; ENITEC Consortium; Xanthoulea S, Romano A. Development of an Image-Guided Orthotopic Xenograft Mouse Model of Endometrial Cancer with Controllable Estrogen Exposure. Int J Mol Sci. 2018 Aug 28;19(9):2547. doi: 10.3390/ijms19092547. PMID: 30154339; PMCID: PMC6165149.

• Halle MK, Tangen IL, Berg HF, Hoivik EA, Mauland KK, Kusonmano K, Berg A, Hurtado A, Kalland KH, Øyan AM, Stefansson I, Vintermyr OK, Werner HM, Haldorsen IS, Trovik J, Salvesen HB, Krakstad C. HER2 expression patterns in paired primary and metastatic endometrial cancer lesions. Br J Cancer. 2018 Feb 6;118(3):378-387. doi: 10.1038/bjc.2017.422. Epub 2017 Nov 23. PMID: 29169184; PMCID: PMC5808034.

• Fonnes T, Berg HF, Bredholt T, Edqvist PD, Sortland K, Berg A, Salvesen HB, Akslen LA, Werner HMJ, Trovik J, Tangen IL, Krakstad C. Asparaginase-like protein 1 is an independent prognostic marker in primary endometrial cancer, and is frequently lost in metastatic lesions. Gynecol Oncol. 2018 Jan;148(1):197-203. doi: 10.1016/j.ygyno.2017.10.025. Epub 2017 Oct 31. PMID: 29096882.

• Fonnes T, Trovik J, Edqvist PH, Fasmer KE, Marcickiewicz J, Tingulstad S, Staff AC, Bjørge L, Amant F, Haldorsen IS, Werner H, Akslen LA, Tangen IL, Krakstad C. Asparaginase-like protein 1 expression in curettage independently predicts lymph node metastasis in endometrial carcinoma: a multicentre study. BJOG. 2018 Dec;125(13):1695-1703. doi: 10.1111/1471-0528.15403. Epub 2018 Aug 19. PMID: 29989298.

• Fasmer KE, Bjørnerud A, Ytre-Hauge S, Grüner R, Tangen IL, Werner HM, Bjørge L, Salvesen ØO, Trovik J, Krakstad C, Haldorsen IS. Preoperative quantitative dynamic contrast-enhanced MRI and diffusion-weighted imaging predict aggressive disease in endometrial cancer. Acta Radiol. 2018 Aug;59(8):1010-1017. doi: 10.1177/0284185117740932. Epub 2017 Nov 14. PMID: 29137496.

• Earp M, Tyrer JP, Winham SJ, Lin HY, Chornokur G, Dennis J,  et al.. Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility. PLoS One. 2018 Jul 6;13(7):e0197561. doi: 10.1371/journal.pone.0197561. PMID: 29979793; PMCID: PMC6034790.

• Holst F, Werner HMJ, Mjøs S, Hoivik EA, Kusonmano K, Wik E, Berg A, Birkeland E, Gibson WJ, Halle MK, Trovik J, Cherniack AD, Kalland KH, Mills GB, Singer CF, Krakstad C, Beroukhim R, Salvesen HB. PIK3CA Amplification Associates with Aggressive Phenotype but Not Markers of AKT-MTOR Signaling in Endometrial Carcinoma. Clin Cancer Res. 2019 Jan 1;25(1):334-345. doi: 10.1158/1078-0432.CCR-18-0452. Epub 2018 Nov 15. PMID: 30442683; PMCID: PMC6384094.

• Kelemen LE, Earp M, Fridley BL, Chenevix-Trench G; Australian Ovarian Cancer Study Group; et al. rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology. Int J Mol Sci. 2018 Aug 21;19(9):2473. doi: 10.3390/ijms19092473. PMID: 30134598; PMCID: PMC6163881.

• O'Mara TA, Glubb DM, Amant F, Annibali D, Ashton K, et al.. Identification of nine new susceptibility loci for endometrial cancer. Nat Commun. 2018 Aug 9;9(1):3166. doi: 10.1038/s41467-018-05427-7. PMID: 30093612; PMCID: PMC6085317.

2024

Kari S. Wagner-Larsen

Advanced MRI for developing more personalized treatment strategies in uterine cervical cancer

Hilde E. Lien

Single cell expression patterns in endometrial cancer and novel biomarkers for improved treatment

2023

Kristine E. Fasmer

MRI and 2-[18F]FDG PET/CT for staging, prognostication, and tailoring treatment in endometrial cancer.

2022

Hege F. Berg

Organoid models and novel biomarkers for improved treatment of endometrial cancer. 

2021

David E. Forsse

Novel preoperative biomarkers and evaluation of altered treatment strategies to improve outcome for endometrial cancer patients.

2020

Hilde R. Engerud

Molecular markers to predict prognosis and guide therapy in endometrial cancer

2019

Sigmund Ytre-Hauge

Advanced imaging biomarkers in endometrial cancer

2018

Tina Fonnes

Preclinical models and molecular biomarkers – tools to improve treatment in endometrial carcinoma

2017

Anna Berg

Molecular alterations and diagnostic imaging in premalignant and malignant endometrial lesions for improved diagnosis and treatment

Karen K. Mauland

Context-related biomarkers in endometrial cancer – a study with focus on obesity and genomic alterations

Mari K. Halle

Molecular alterations suggesting new treatment strategies in uterine carcinomas

2013

Elisabeth Wik

Endometrial carcinoma: a step closer to individualized therapy? Exploring transcriptional alterations in relation to prognostic biomarkers

Even Birkeland

Mutations and gene amplifications in Endometrial Carcinomas. “Clinical characteristics and potential targets for therapyrelated to KRAS, MYC, ATAD2, PIK3CA and FGFR2 alterations

2012

Jone Trovik

Endometrial cancer; can biomarkers aid in the prediction of aggressive disease? A study with focus on preoperative tumour markers

For tiden har 14 doktorgradsstudenter fullført sin doktorgrad i vår forskningsgruppe.

2024

Marit Louise Ulvang

HER2, Tissue factor, TROP2 and NECTIN4 as targets for antibody-drug conjugate (ADC) therapy in cervical cancer

2021

Marta E. Hjelmeland

Endometrial cancer organoids as preclinical models for drug screening

Marte Sødal

Molecular alterations suggesting new treatment strategies for cervical cancer patients