Camilla Krakstad

• PhD
• Professor (Full) at University of Bergen

Purpose: The expression and involvement of estrogen (ER) and progesterone receptor (PR) is extensively studied in endometrial cancer. Androgen receptor (AR) is a hormone receptor less studied in female cancers, and we here aim to investigate the expression level of AR in endometrial cancer precursor lesions, primary tumors and metastases, and its...

Recent studies have detailed the genomic landscape of primary endometrial cancers, but the evolution of these cancers into metastases has not been characterized. We performed whole-exome sequencing of 98 tumor biopsies including complex atypical hyperplasias, primary tumors and paired abdominopelvic metastases to survey the evolutionary landscape o...

Background: Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metastatic spread. Novel preclinical imaging methods also have the potential to quantify functional tumour characteristics in vivo, with potential relevance for monitoring response to therapy. Methods: After orthotopic injection with luc-expre...

Endometrial cancer incidence is increasing, due in part to a strong association with obesity. Mutations in the phosphatidylinositol 3-kinase (PI3K) pathway, the central relay pathway of insulin signals, occur in the majority of endometrioid adenocarcinomas, the most common form of endometrial cancer. We sought to determine the impact of PI3K pathwa...

Cervical cancer is responsible for 10-15% of cancer-related deaths in women worldwide. The aetiological role of infection with high-risk human papilloma viruses (HPVs) in cervical carcinomas is well established. Previous studies have also implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as several copy-number alterations i...

Pelvic MRI is essential for evaluating local and regional tumor extent in uterine cervical cancer (CC). Tumor microstructure captured by diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) markers may be closely linked to prognosis in CC. Purpose To explore whether primary tumor ADC markers predict survival in CC. Material and...

Objective: This study aimed to evaluate the association between pre-operative progesterone receptor (PR) and p53 expression and prognosis in pre-operative grade 2 endometrioid endometrial carcinoma compared with grade 1 and grade 3 carcinomas. Methods: Three European endometrial carcinoma cohort studies were included. Patients with pre-operative...

The presence of cancer stem cells is linked to aggressive disease and higher risk of recurrence, and multiple markers have been proposed to detect cancer stem cells. However, a detailed evaluation of the expression patterns and the prognostic value of markers relevant for endometrial cancer is lacking. As organoid models are suggested to be enriche...

Background Effective diagnostic tools for prompt identification of high-risk locally advanced cervical cancer (LACC) patients are needed to facilitate early, individualized treatment. The aim of this work was to assess temporal changes in tumor radiomics (delta radiomics) from T2-weighted imaging (T2WI) during concurrent chemoradiotherapy (CCRT) in...

Background Precise preoperative risk classification of endometrial cancer is crucial for treatment decisions. Existing clinical markers often fail to accurately predict lymph node metastasis and recurrence risk. Loss of vimentin expression has emerged as a potential marker for predicting recurrence in low-risk endometrial cancer patients. We assess...

This study reanalyzes epidermal growth factor receptor 2 (ERBB2) data from a previous study to characterize patient subgroups with ERBB2-low tumors.

Objective Although early-detected cervical cancer is associated with good survival, the prognosis for late-stage disease is poor and treatment options are sparse. Mismatch repair deficiency (MMR-D) has surfaced as a predictor of prognosis and response to immune checkpoint inhibitor(s) in several cancer types, but its value in cervical cancer remain...

Background: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored...

Cervical cancer (CC) is a major global health problem with 570,000 new cases and 266,000 deaths annually. Prognosis is poor for advanced stage disease, and few effective treatments exist. Preoperative diagnostic imaging is common in high-income countries and MRI measured tumor size routinely guides treatment allocation of cervical cancer patients....

Background Radiomics can capture microscale information in medical images beyond what is visible to the naked human eye. Using a clinically relevant mouse model for endometrial cancer, the objective of this study was to develop and validate a radiomic signature (RS) predicting response to standard chemotherapy. Methods Mice orthotopically implante...

High-grade neuroendocrine cervical cancers (NETc) are exceedingly rare, highly aggressive tumors. We analyzed 64 NETc tumor samples by whole-exome sequencing (WES). Human papillomavirus DNA was detected in 65.6% (42/64) of the tumors. Recurrent mutations were identified in PIK3CA, KMT2D/MLL2, K-RAS, ARID1A, NOTCH2, and RPL10. The top mutated genes...

Introduction/Background Radiomics can capture microscale information in medical images beyond what is visible to the naked human eye. Using a clinically relevant mouse model for endometrial cancer, the objective of this study was to develop and validate a radiomic signature (RS) predicting response to standard chemotherapy. Methodology Mice orthot...

Introduction/Background The objectives of this study was to quantify abdominal obesity markers from computed tomography (CT) scans at primary diagnosis and follow-up in a large endometrial cancer cohort, and to assess temporal change in obesity markers in relation to clinical phenotype and outcome. Methodology Total- (TAV), subcutaneous- (SAV), vi...

Introduction/Background There is no clear guidance for systemic treatment in patients with advanced/recurrent endometrial cancer (EC). Hormonal therapies can be considered in a palliative setting, yet there is a lack of biomarkers to predict a therapeutic response to the drug. This study aimed to identify effective biomarkers from tumor transcripto...

Introduction/Background Recent guidelines propose a binary grading for endometrial cancer (EC) in low- or high grade, in which all endometrioid EC (EEC) grade 1 and 2 are considered low-grade and treated accordingly. However, pre- and postoperative agreement was the lowest in grade 2 with clinically relevant upgrading in 14% in a previously publish...

Introduction/Background Introduction: Endometrial cancer (EC) constitutes the fourth most common cancer among women in Europe, and in recent years its incidence has increased significantly. Despite good prognosis for patients with localized disease, about 20% of patients classified as low-risk at surgery, experience disease recurrence. Unfortunatel...

Introduction/Background Analysis of circulating tumour DNA (ctDNA) is a promising non-invasive technique that may serve as a diagnostic, prognostic, and disease-monitoring marker. Aim of this study is to investigate the association of ctDNA with clinicopathological characteristics and oncological outcome in endometrial cancer patients. Methodology...

Objectives Widespread clinical use of MRI radiomic tumor profiling for prognostication and treatment planning in cancers faces major obstacles due to limitations in standardization of radiomic features. The purpose of the current work was to assess the impact of different MRI scanning- and normalization protocols for the statistical analyses of tum...

Background Accurate pretherapeutic prognostication is important for tailoring treatment in cervical cancer (CC). Purpose To investigate whether pretreatment MRI‐based radiomic signatures predict disease‐specific survival (DSS) in CC. Study Type Retrospective. Population CC patients ( n = 133) allocated into training (T) ( n T = 89)/validation (V...

Introduction/Background We recently identified low vimentin as a marker of recurrence in low-stage endometrial cancers (Lien et al. eBioMedicine, Volume 92, 2023). Such markers are currently lacking in clinical use and could improve treatment for patients with undetected high-risk of recurrence. We aimed to validate the robustness of vimentin as a...

Introduction/Background Pelvic magnetic resonance imaging (MRI) is an important part of primary diagnostic workup in cervical cancer (CC), with MRI-assessed tumour size and pelvic tumour extent routinely guiding treatment decisions. Extraction of MRI-derived radiomic tumour features could improve cancer prognostics and may also reveal novel targets...

Objective: The prognostic role of adiposity in uterine cervical cancer (CC) is largely unknown. Abdominal fat distribution may better reflect obesity than body mass index. This study aims to describe computed tomography (CT)-assessed abdominal fat distribution in relation to clinicopathologic characteristics, survival, and tumor gene expression in...

Background: High-grade serous ovarian carcinoma (HGSOC) is the deadliest ovarian cancer subtype, and survival relates to initial cytoreductive surgical treatment. The existing tools for surgical outcome prediction remain inadequate for anticipating the outcomes of the complex relationship between tumour biology, clinical phenotypes, co-morbidity a...

Simple Summary Patients with high-grade uterine cancer (UC) have a risk of around 20% of the cancer spreading to the lymph nodes, while this is only around 10% in patients with low-grade uterine cancer. CA125 is a marker that can be detected in blood and is associated with increased tumor spread. Studies on CA125 and its association with tumor spre...

Background: Identification of aggressive low-stage endometrial cancers is challenging. So far, studies have failed to pinpoint robust features or biomarkers associated with risk of recurrence for these patients. Methods: Imaging mass cytometry was used to examine single-cell expression of 23 proteins in 36 primary FIGO IB endometrial cancers, of...

Several studies have highlighted the frequent alterations of the PI3K pathway in endometrial cancer leading to increased signaling activation with potential for targeted treatment. The objective of this meta-study was to evaluate how PIK3CA exon 9/20 mutations affect survival in endometrial cancer patients, based on available literature. Topic-base...

Objectives Patient-derived cancer organoids have quickly developed as valuable tools for drug testing as they better represent the genetic background of the patient cohort. We recently published a protocol for establishing EC organoids from all types and grades of EC (Berg et al, Nat Comms Med 2021). We here present data from a prospectively collec...

Objectives To explore the diagnostic accuracy of preoperative magnetic resonance imaging (MRI)-derived tumor measurements for the prediction of histopathological deep (≥ 50%) myometrial invasion (pDMI) and prognostication in endometrial cancer (EC). Methods Preoperative pelvic MRI of 357 included patients with histologically confirmed EC were read...

Background The endometrial cancer mismatch repair (MMR) deficient subgroup is defined by loss of MSH6, MSH2, PMS2 or MLH1. We compare MMR status in paired preoperative and operative samples and investigate the prognostic impact of differential MMR protein expression levels. Methods Tumour lesions from 1058 endometrial cancer patients were immunohi...

Background: A common 30 kb deletion affecting the APOBEC3A and APOBEC3B genes has been linked to increased APOBEC activity and APOBEC-related mutational signatures in human cancers. The role of this deletion as a cancer risk factor remains controversial. Materials and methods: We genotyped the APOBEC3A/B deletion in a sample of 1,470 Norwegian e...

Introduction/Background The updated FIGO (2018) staging system incorporates diagnostic imaging and pathology results into stage assignment in cervical cancer (CC). This study aims to evaluate the extent and source of stage migration when exchanging FIGO (2009) with FIGO (2018) in a large CC cohort and compare the prognostic performance of FIGO (200...

Introduction/Background The aim of this study was to explore abdominal fat distribution markers from computed tomography (CT) in relation to clinicopathologic characteristics and patient outcome in uterine cervical cancer (CC). By unravelling possible links between fat distribution profiles and altered tumour signalling pathways, potential molecula...

Introduction/Background Although early detected cervical cancer is associated with good survival, prognosis for late-stage disease is poor and treatment options are sparse. Mismatch-repair (MMR) deficiency has surfaced as a predictor of immune checkpoint inhibitor responses in several cancer types, but its value in cervical cancer remains unclear....

Introduction/Background NRIP1, encoding an obligate cofactor to the estrogen receptor alpha (ERα), is a significantly mutated gene in endometrial cancer (EC) with possible implications on hormone signaling and cancer development. We aimed at determining the prognostic impact of NRIP1 mutations and mRNA expression in patients with ERα-positive EC, a...

Introduction/Background Using clinically relevant imaging modalities in relevant animal models is crucial for strengthening the translational value of preclinical discoveries in endometrial cancer (EC). Imaging by ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) is commonly used in diagnostic work-up in EC. ¹...

Introduction/Background Alternative treatment options for endometrial cancer (EC) when chemotherapy fails are few. We have previously demonstrated the prognostic impact of Androgen receptor (AR) expression in EC (Tangen et al., 2016). However, the therapeutic potential of targeting AR in EC is not known. Patient-derived cancer organoids have recent...

Objective: This study presents the diagnostic performance of four different preoperative imaging workups (IWs) for prediction of lymph node metastases (LNMs) in endometrial cancer (EC): pelvic MRI alone (IW1), MRI and [18F]FDG-PET/CT in all patients (IW2), MRI with selective [18F]FDG-PET/CT if high-risk preoperative histology (IW3), and MRI with s...

Magnetic resonance imaging (MRI) has emerged as an important part of the diagnostic work-up in cervical cancer, with tumor volume and extent as important prognosticators. MRI radiomic tumor features may aid in prognostication and tailoring of treatment in cervical cancer. We extracted whole-volume radiomic texture features from 124 manually segment...

Patients with localized endometrial carcinomas (FIGO IA and IB) have a 5-year relative survival rate of > 90%. Still, some patients with an expected good prognosis experience recurrence of disease which dramatically reduces survival rates. Currently, we lack the knowledge to predict which patients will get recurrence. We used Imaging Mass Cytometry...

Background Tumor size assessment by MRI is central for staging uterine cervical cancer. However, the optimal role of MRI-derived tumor measurements for prognostication is still unclear. Material and methods This retrospective cohort study included 416 women (median age: 43 years) diagnosed with cervical cancer during 2002–2017 who underwent pretre...

Uterine cervical cancer (CC) is the most common gynecologic malignancy worldwide. Whole-volume radiomic profiling from pelvic MRI may yield prognostic markers for tailoring treatment in CC. However, radiomic profiling relies on manual tumor segmentation which is unfeasible in the clinic. We present a fully automatic method for the 3D segmentation o...

Objectives To evaluate the interobserver agreement for MRI–based 2018 International Federation of Gynecology and Obstetrics (FIGO) staging parameters in patients with cervical cancer and assess the prognostic value of these MRI parameters in relation to other clinicopathological markers. Methods This retrospective study included 416 women with his...

Implementation of high-risk human papilloma virus (HPV) screening and the increasing proportion of HPV vaccinated women in the screening program will reduce the percentage of HPV positive women with oncogenic potential. In search of more specific markers to identify women with high risk of cancer development, we used RNA sequencing to compare the t...

Prognostication is critical for accurate diagnosis and tailored treatment in endometrial cancer (EC). We employed radiogenomics to integrate preoperative magnetic resonance imaging (MRI, n = 487 patients) with histologic-, transcriptomic- and molecular biomarkers (n = 550 patients) aiming to identify aggressive tumor features in a study including 8...

Human papillomavirus (HPV)-associated cervical cancer represents one of the leading causes of cancer death worldwide. Although low-middle income countries are disproportionately affected, our knowledge of the disease predominantly originates from populations in high-income countries. Using the largest multi-omic analysis of cervical squamous cell c...

Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries. The main challenge in EC management is to correctly estimate the risk of metastases at diagnosis and the risk to develop recurrences in the future. Risk stratification determines the need for surgical staging and adjuvant treatment. Detection of occult, micro...

The purpose of this study was to establish a gene signature that may predict CIN3 regression and that may aid in selecting patients who may safely refrain from conization. Oncomine mRNA data including 398 immune-related genes from 21 lesions with confirmed regression and 28 with persistent CIN3 were compared. L1000 mRNA data from a cervical cancer...

Introduction/Background* Patients with high-grade endometrial carcinoma (EC) have an increased risk of lymph node metastasis (LNM). Preoperative serum CA125 and imaging findings have been incorporated in multiple risk stratification models to predict LNM and advanced disease in EC and are widely used in clinical practice. However, data on their pre...

Background Pelvic magnetic resonance imaging (MRI) and whole-body positron emission tomography-computed tomography (PET-CT) play an important role at primary diagnostic work-up and in detecting recurrent disease in endometrial cancer (EC) patients, however the preclinical use of these imaging methods is currently limited. We demonstrate the feasibi...

Cervical cancer tumors with undetectable HPV (HPVU) have been underappreciated in clinical decision making. In this study, two independent CC datasets were used to characterize the largest cohort of HPVU tumors to date (HPVU = 35, HPV+ = 430). Genomic and transcriptome tumor profiles and patient survival outcomes were compared between HPV+ and HPVU...

Endometriosis, polycystic ovary syndrome (PCOS) and uterine fibroids have been proposed as endometrial cancer risk factors; however, disentangling their relationships with endometrial cancer is complicated due to shared risk factors and comorbidities. Using genome-wide association study (GWAS) data, we explored the relationships between these non-c...

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Background Most endometrial cancer patients with localized disease are effectively treated and survive for a long time. Primary treatment is hysterectomy, to which surgical staging procedures may be added to assess the need for adjuvant therapy. Longitudinal data on patient-reported outcomes comparing different levels of primary treatment is lackin...

Background A major hurdle in translational endometrial cancer (EC) research is the lack of robust preclinical models that capture both inter- and intra-tumor heterogeneity. This has hampered the development of new treatment strategies for people with EC. Methods EC organoids were derived from resected patient tumor tissue and expanded in a chemica...

Background Around 20% of women with endometrial cancer have advanced stage disease or suffer from a recurrence. For these women, prognosis is poor and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall...

Background: Pelvic magnetic resonance imaging (MRI) and whole-body positron emission tomography-computed tomography (PET-CT) play an important role at primary diagnostic work-up and in detecting recurrent disease in endometrial cancer (EC) patients, however the preclinical use of these imaging methods is currently limited. We demonstrate the feasib...

Objective Pre-operative immunohistochemical (IHC) biomarkers are not incorporated in endometrial cancer (EC) risk classification. We aim to investigate the added prognostic relevance of IHC biomarkers to the ESMO-ESGO-ESTRO risk classification and lymph node (LN) status in EC. Methods Retrospective multicenter study within the European Network for...

Background Advanced cervical cancer carries a particularly poor prognosis, and few treatment options exist. Identification of effective molecular markers is vital to improve the individualisation of treatment. We investigated transcriptional data from cervical carcinomas related to patient survival and recurrence to identify potential molecular dri...

The class I phosphoinositide 3-kinase (PI3K) catalytic subunits p110α and p110β are ubiquitously expressed but differently targeted in tumours. In cancer, PIK3CB (encoding p110β) is seldom mutated compared with PIK3CA (encoding p110α) but can contribute to tumorigenesis in certain PTEN-deficient tumours. The underlying molecular mechanisms are, how...

Integrative tumor characterization linking radiomic profiles to corresponding gene expression profiles has the potential to identify specific genetic alterations based on non-invasive radiomic profiling in cancer. The aim of this study was to develop and validate a radiomic prognostic index (RPI) based on preoperative magnetic resonance imaging (MR...

Preoperative MR imaging in endometrial cancer patients provides valuable information on local tumor extent, which routinely guides choice of surgical procedure and adjuvant therapy. Furthermore, whole-volume tumor analyses of MR images may provide radiomic tumor signatures potentially relevant for better individualization and optimization of treatm...

Objectives There is a need for more knowledge about the public awareness and attitudes towards gynecologic cancers. We employed a research-purpose population-based citizen panel to assess how often people recall gynecologic cancers compared to other cancer types and to explore the relative importance of different information channels in relaying ca...

Objective Main controversies in endometrial cancer treatment include the role of lymphadenectomy and optimal adjuvant treatment. We assessed clinical outcome in a population-based endometrial cancer cohort in relation to changes in treatment management over two decades. Methods All consenting endometrial cancer patients receiving primary treatment...

Background there is no consensus on the cut-off for positivity of estrogen receptor (ER) and progesterone receptor (PR) in endometrial cancer (EC). Therefore we determined the cut-off value for ER and PR with the strongest prognostic impact on outcome. Methods immunohistochemical expression of ER and PR was scored as a percentage of positive EC ce...

Better understanding of the complex processes driving tumor growth and metastases is critical for developing targeted treatment strategies in cancer. Radiomics extracts large amounts of features from medical images which enables radiomic tumor profiling in combination with clinical markers. However, analyzing complex imaging data in combination wit...

Background In endometrial cancer (EC), preoperative pelvic MRI is recommended for local staging, while final tumor stage and grade are established by surgery and pathology. MRI‐based radiomic tumor profiling may aid in preoperative risk‐stratification and support clinical treatment decisions in EC. Purpose To develop MRI‐based whole‐volume tumor r...

Background: To enable more individualised treatment of endometrial cancer, improved methods for preoperative tumour characterization are warranted. Texture analysis is a method for quantification of heterogeneity in images, increasingly reported as a promising diagnostic tool in oncological imaging, but largely unexplored in endometrial cancer AIM...

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two‐sample Mendelian rando...

Endometrial cancer (EC) is the fifth most common cancer in women worldwide. Global estimates show rising incidence rates in both developed and developing countries. Most women are diagnosed postmenopausal, but 14-25% of patients are premenopausal and 5% are under 40 years of age. Established risk factors include age and hyperestrogenic status assoc...

We report a meta-analysis of breast, prostate, ovarian, and endometrial cancer genome-wide association data (effective sample size: 237,483 cases/317,006 controls). This identified 465 independent lead variants ( P <5x10 ⁻⁸ ) across 192 genomic regions. Four lead variants were >1Mb from previously identified risk loci for the four cancers and an ad...

Introduction: Comprehensive profiling of tumors using omics technologies has improved our understanding of the molecular landscape of endometrial cancer (EC), building the foundation for precision medicine. However, targeted therapies that show promise in preclinical research are failing clinical trials, which is partly explained by the lack of mod...

Background Bayesian networks (BNs) are machine-learning–based computational models that visualize causal relationships and provide insight into the processes underlying disease progression, closely resembling clinical decision-making. Preoperative identification of patients at risk for lymph node metastasis (LNM) is challenging in endometrial cance...

Objectives This review examines how response rates to progestin treatment of low-grade endometrial cancer can be improved. In addition to providing a brief overview of the pathogenesis of low-grade endometrial cancer, we discuss limitations in the current classification of endometrial cancer and how stratification may be refined using molecular mar...

Human papillomavirus (HPV)-associated cervical cancer represents one of the leading causes of cancer death worldwide. Although low-middle income countries are disproportionately affected, our knowledge of the disease predominantly originates from populations in high-income countries. Using the largest multi-omic analysis of cervical squamous cell c...

In endometrioid endometrial cancer (EEC), current clinical algorithms do not accurately predict patients with lymph node metastasis (LNM), leading to both under- and over-treatment. We aimed to develop models that integrate protein data with clinical information to identify patients requiring more aggressive surgery, including lymphadenectomy. Prot...

Objectives To compare the diagnostic accuracy of preoperative 18F-FDG PET/CT and MRI tumor markers for prediction of lymph node metastases (LNM) and aggressive disease in endometrial cancer (EC).Methods Preoperative whole-body 18F-FDG PET/CT and pelvic MRI were performed in 215 consecutive patients with histologically confirmed EC. PET/CT-based tum...

Objective: PD-L1 and PD-1 are predictive markers for immunotherapy and increasingly relevant in endometrial cancer. The reported fraction of positive primary tumors has been inconsistent. We investigated the expression of PD-L1 and PD-1 in primary tumors, also stratified by MSI. As immunotherapy is foremost relevant for metastatic disease, PD-L1 a...