| 1. |
- O'Mara, TA, et al.
(författare)
-
Identification of nine new susceptibility loci for endometrial cancer
- 2018
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 3166-
-
Tidskriftsartikel (refereegranskat)abstract
- Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.
|
|
| 2. |
- Cheng, THT, et al.
(författare)
-
Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
- 2015
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 17369-
-
Tidskriftsartikel (refereegranskat)abstract
- High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Hveem, T. S., et al.
(författare)
-
Changes in Chromatin Structure in Curettage Specimens Identifies High-Risk Patients in Endometrial Cancer
- 2017
-
Ingår i: Cancer Epidemiology Biomarkers & Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 26:1, s. 61-67
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Most endometrial carcinoma patients are diagnosed at an early stage with a good prognosis. However, a relatively low fraction with lethal disease constitutes a substantial number of patients due to the high incidence rate. Preoperative identification of patients with high risk and low risk for poor outcome is necessary to tailor treatment. Nucleotyping refers to characterization of cell nuclei by image cytometry, including the assessment of chromatin structure by nuclear texture analysis. This method is a strong prognostic marker in many cancers but has not been evaluated in preoperative curettage specimens from endometrial carcinoma. Methods: The prognostic impact of changes in chromatin structure quantified with Nucleotyping was evaluated in preoperative curettage specimens from 791 endometrial carcinoma patients prospectively included in the MoMaTEC multicenter trial. Results: Nucleotyping was an independent prognostic marker of disease-specific survival in preoperative curettage specimens among patients with Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage I-II disease (HR = 2.9; 95% CI, 1.2-6.5; P - 0.013) and significantly associated with age, FIGO stage, histologic type, histologic grade, myometrial infiltration, lymph node status, curettage histology type, and DNA ploidy. Conclusions: Nucleotyping in preoperative curettage specimens is an independent prognostic marker for disease-specific survival, with potential to supplement existing parameters for risk stratification to tailor treatment. Impact: This is the first study to evaluate the prognostic impact of Nucleotyping in curettage specimens from endometrial carcinoma and shows that this may be a clinically useful prognostic marker in endometrial cancer. External validation is warranted. (C) 2016 AACR.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Werner, H M J, et al.
(författare)
-
A discordant histological risk classification in preoperative and operative biopsy in endometrial cancer is reflected in metastatic risk and prognosis.
- 2013
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 49:3, s. 625-632
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: In endometrial cancer, tissue for histological evaluation is obtained preoperatively (endometrial biopsy) and operatively (hysterectomy specimen). We investigated if a discordant risk classification based on preoperative and operative biopsy is reflected in metastatic risk and prognosis. PATIENTS AND METHODS: One thousand three hundred and seventy-four patients were prospectively included in a multicentre setting (Molecular Markers for Treatment of Endometrial Cancer (MoMaTEC) study). Preoperative and operative specimens were classified as high risk if non-endometrioid histology or endometrioid grade 3; otherwise low risk. Disease specific survival differences were calculated by means of Kaplan-Meier and Cox proportional hazard models. RESULTS: Discordant risk was found in 207 (16%) cases. Lymph node metastases were detected in 7% and 23% of patients with concordant low and high risk respectively versus 14% and 20% in the discordant groups (p<0.001). Five-year disease specific survival in the discordant groups proved intermediate (75-80%) to concordant low (94%) or high (58%) risk. Both operative and preoperative biopsy high-risk results have independent prognostic impact on disease specific survival with adjusted hazard ratios of 2.4 (95% confidence interval (95% CI) 1.5-3.9) and 2.1 (95% CI 1.3-3.2) respectively by Cox analysis. CONCLUSIONS: Discordant risk in preoperative biopsy and hysterectomy identifies an intermediate group with respect to disease spread and prognosis. Preoperative biopsy results remain important also with the hysterectomy histology available.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Njolstad, T. S., et al.
(författare)
-
DNA ploidy in curettage specimens identifies high-risk patients and lymph node metastasis in endometrial cancer
- 2015
-
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 112:10, s. 1656-1664
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Preoperative risk stratification is essential in tailoring endometrial cancer treatment, and biomarkers predicting lymph node metastasis and aggressive disease are aspired in clinical practice. DNA ploidy assessment in hysterectomy specimens is a well-established prognostic marker. DNA ploidy assessment in preoperative curettage specimens is less studied, and in particular in relation to the occurrence of lymph node metastasis. Methods: Curettage image cytometry DNA ploidy in relation to established clinicopathological variables and outcome was investigated in 785 endometrial carcinoma patients prospectively included in the MoMaTEC multicentre trial. Results: Diploid curettage status was found in 72.0%, whereas 28.0% were non-diploid. Non-diploid status significantly correlated with traditional aggressive postoperative clinicopathological features, and was an independent predictor of lymph node metastasis among FIGO stage I-III patients in multivariate analysis (OR 1.94, P = 0.033). Non-diploid status was related to shorter disease-specific survival (5-year DSS of 74.4% vs 88.8% for diploid curettage, P<0.001). When stratifying by FIGO stage and lymph node status, the prognostic effect remained. However, in multivariate regression analysis, preoperative histological risk classification was a stronger predictor of DSS than DNA ploidy. Conclusions: Non-diploid curettage is significantly associated with aggressive clinicopathological phenotype, lymph node metastasis, and poor survival in endometrial cancer. The prognostic effect was also observed among subgroups with (presumably) less aggressive traits, such as low FIGO stage and negative lymph node status. Our results indicate curettage DNA ploidy as a possible supplement to existing parameters used to tailor surgical treatment. ELER VM, 1991, CANCER, V67, P3093
|
|
| 17. |
- Fonnes, T., et al.
(författare)
-
Asparaginase-like protein 1 expression in curettage independently predicts lymph node metastasis in endometrial carcinoma: a multicentre study
- 2018
-
Ingår i: Bjog-an International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 125:13, s. 1695-1703
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Design Correct preoperative identification of high-risk patients is important to optimise surgical treatment and improve survival. We wanted to explore if asparaginase-like protein 1 (ASRGL1) expression in curettage could predict lymph node metastases and poor outcome, potentially improving preoperative risk stratification. Multicentre study. Setting Population Ten hospitals in Norway, Sweden and Belgium. Women diagnosed with endometrial carcinoma. Methods Main outcome measures ASRGL1 expression in curettage specimens from 1144 women was determined by immunohistochemistry. ASRGL1 status related to disease-specific survival, lymph node status, preoperative imaging parameters and clinicopathological data. Results Conclusions ASRGL1 expression had independent prognostic value in multivariate survival analyses, both in the whole patient population (hazard ratio (HR) 1.63, 95% CI 1.11-2.37, P = 0.012) and in the low-risk curettage histology subgroup (HR 2.54, 95% CI 1.44-4.47, P = 0.001). Lymph node metastases were more frequent in women with low expression of ASRGL1 compared with women with high ASRGL1 levels (23% versus 10%, P < 0.001), and low ASRGL1 level was found to independently predict lymph node metastases (odds ratio 2.07, 95% CI 1.27-3.38, P = 0.003). Low expression of ASRGL1 in curettage independently predicts lymph node metastases and poor disease-specific survival.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Njolstad, T. S., et al.
(författare)
-
Late-week surgical treatment of endometrial cancer is associated with worse long-term outcome: Results from a prospective, multicenter study
- 2017
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:8
-
Tidskriftsartikel (refereegranskat)abstract
- Surgery is the cornerstone in primary endometrial cancer treatment, and with curative intent it constitutes total hysterectomy and bilateral salpingo-oopherectomy. In addition, lympha-denectomy is performed in selected patients dependent on a preoperative risk assessment. Recent reports from the surgical approach to esophageal cancer reveal worse outcome when esophagectomy is performed later in the week. On this basis, we set out to explore weekday of surgery in relation to long-term outcome in 1302 endometrial cancer patients prospectively included in the MoMaTEC multicenter study. Day of surgery was dichotomized as early-week (Monday-Tuesday) or late-week (Wednesday-Friday), and evaluated as a discrete variable. Adjusted for patient age, Body Mass Index (BMI), FIGO stage, and histology, surgery performed later in the week was associated with 50.9% increased risk of all-cause death (p = 0.029). Among high-stage patients (FIGO stage III and IV), 5-year disease-specific survival proportions were 53.0% for early-week operated vs. 40.2% for lateweek operated (p = 0.005 for difference). In multivariate survival analysis of high-stage patients, late-week surgery correlated with an increased risk of disease-specific death by 88.7% and all-cause death by 76.4% (p<0.017). Evaluating only patients who underwent lymphadenectomy, the adverse prognostic effect of being operated late-week remained for both disease-specific and all-cause death (HR 2.151 and HR 1.912, p = 0.004). Whether surgery was performed early- or late-week was not influenced by patient age, BMI, preoperative histology risk classification, FIGO stage or postoperative histology (all p>0.05). In conclusion, endometrial cancer surgery conducted late-week is associated with worse long-term outcome. Our findings are most evident among patients with higher FIGO stages, and patients who underwent more extensive surgical procedure (lymphadenectomy). With support from other studies, our results suggest that high-risk patients may benefit from surgery earlier in the week.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Werner, H M J, et al.
(författare)
-
Revision of FIGO surgical staging in 2009 for endometrial cancer validates to improve risk stratification.
- 2012
-
Ingår i: Gynecologic oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 125:1, s. 103-108
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Correct staging is a cornerstone in cancer treatment. The FIGO surgical staging for endometrial cancer was revised in 2009. We have evaluated if the revision improved stratification with respect to prognosis in a large prospective multicenter setting. METHODS: 1268 endometrial cancer patients have been prospectively recruited in the MoMaTEC study for the investigation of clinical and histopathological data. RESULTS: Restaging from FIGO 88 to FIGO 09 criteria increased the number of stage I cases from 932 to 979. The majority of the non-endometrioid tumors, down-staged to FIGO 09 stage I, were of serous histology. One third of the patients classified as stage II tumors based on FIGO 88 criteria (FIGO88 IIA) were down-staged to FIGO 09 IA (53%) and FIGO 09 IB (47%). The histological subtype for these cases was mainly endometrioid (86.1%) and high/intermediate grade (77.7%). Patients with FIGO 88 stages IA, IB, IIA and IIIA with positive cytology only, showed similar survival. In Cox multivariate survival analysis adjusting for histopathological variables we found that the revised FIGO 09 criteria improved prognostication. For FIGO stage I patients the adjusted HR was 3.9 (p=0.01, CI 1.35-11.36) for FIGO IB compared to FIGO IA. The independent prognostic impact for the FIGO 09 staging was also confirmed in a subset analysis of patients not subjected to lymphadenectomy and for the endometrioid subgroup. CONCLUSIONS: The FIGO 2009 staging system has improved prediction of prognosis, and is less complex, compared to earlier versions. Careful assessment of myometrial invasion seems particularly important for patients not subjected to lymphadenectomy.
|
|
| 24. |
|
|
| 25. |
- Dutt, Amit, et al.
(författare)
-
Drug-sensitive FGFR2 mutations in endometrial carcinoma
- 2008
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:25, s. 8713-8717
-
Tidskriftsartikel (refereegranskat)abstract
- Oncogenic activation of tyrosine kinases is a common mechanism of carcinogenesis and, given the druggable nature of these enzymes, an attractive target for anticancer therapy. Here, we show that somatic mutations of the fibroblast growth factor receptor 2 (FGFR2) tyrosine kinase gene, FGFR2, are present in 12% of endometrial carcinomas, with additional instances found in lung squamous cell carcinoma and cervical carcinoma. These FGFR2 mutations, many of which are identical to mutations associated with congenital craniofacial developmental disorders, are constitutively activated and oncogenic when ectopically expressed in NIH 3T3 cells. Inhibition of FGFR2 kinase activity in endometrial carcinoma cell lines bearing such FGFR2 mutations inhibits transformation and survival, implicating FGFR2 as a novel therapeutic target in endometrial carcinoma.
|
|
| 26. |
- Fonnes, Tina, et al.
(författare)
-
Asparaginase-like protein 1 is an independent prognostic marker in primary endometrial cancer, and is frequently lost in metastatic lesions
- 2018
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 148:1, s. 197-203
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveLoss of Asparaginase-like protein 1 (ASRGL1) has been suggested as a prognostic biomarker in endometrial carcinoma. Our objective was to validate this in a prospectively collected, independent patient cohort, and evaluate ASRGL1 expression in endometrial carcinoma precursor lesion and metastases.Methods782 primary endometrial carcinomas, 90 precursor lesions (complex atypical hyperplasia), and 179 metastases (from 87 patients) were evaluated for ASRGL1 expression by immunohistochemistry in relation to clinical and histopathological data. ASRGL1 mRNA level was investigated in 237 primary tumors and related to survival and ASRGL1 protein expression.ResultsLow expression of ASRGL1 protein and ASRGL1 mRNA predicted poor disease specific survival (P < 0.001). In multivariate survival analyses ASRGL1 had independent prognostic value both in the whole patient cohort (Hazard ratio (HR): 1.53, 95% confidence interval (CI): 1.04–2.26, P = 0.031) and within the endometrioid subgroup (HR: 2.64, CI: 1.47–4.74, P = 0.001). Low ASRGL1 expression was less frequent in patients with low grade endometrioid primary tumors compared to high grade endometrioid and non-endometrioid primary tumors, and ASRGL1 was lost in the majority of metastatic lesions.ConclusionsIn a prospective setting ASRGL1 validates as a strong prognostic biomarker in endometrial carcinoma. Loss of ASRGL1 is associated with aggressive disease and poor survival, and is demonstrated for the first time to have independent prognostic value in the entire endometrial carcinoma patient population.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
- Wedin, Rikard, et al.
(författare)
-
Complications and survival after surgical treatment of 214 metastatic lesions of the humerus
- 2012
-
Ingår i: Journal of Shoulder and Elbow Surgery. - : Elsevier BV. - 1058-2746 .- 1532-6500. ; 21:8, s. 1049-1055
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The humerus is the second most common long-bone site of metastatic bone disease. We report complications, risk factors for failure, and survival of a large series of patients operated on for skeletal metastases of the humerus. Materials and methods: This study was based on 208 patients treated surgically for 214 metastatic lesions of the humerus. Reconstructions were achieved by intramedullary nails in 148, endoprostheses in 35, plate fixation in 21, and by other methods in 10. Results: The median age at surgery was 67 years (range, 29-87 years). Breast cancer was the primary tumor in 31%. The overall failure rate of the surgical reconstructions was 9%. The reoperation rate was 7% in the proximal humerus, 8% in the diaphysis, and 33% in the distal part of the bone. Among 36 operations involving an endoprosthesis, 2 were failures (6%) compared with 18 of 178 osteosynthetic devices (10%). In the osteosynthesis group, intramedullary nails failed in 7% and plate fixation failed in 22%. Multivariate Cox regression analysis showed that prostate cancer was associated with an increased risk of failure after surgery (hazard ratio, 7; P < 0.033). The cumulative survival after surgery was 40% (95% confidence interval [CI] 34-47) at 1 year, 21% (95% CI, 15-26) at 2 years, and 16% (95% CI, 12-19) at 3 years. Conclusions: Our method of choice is the cemented hemiprosthesis for pathologic proximal humeral fractures and interlocked intramedullary nail for lesions in the diaphysis. Pathologic fractures in the distal humerus are uncommon and associated with a very high reoperation rate. Level of evidence: Level IV, Case Series, Treatment Study. (C) 2012 Journal of Shoulder and Elbow Surgery Board of Trustees.
|
|
| 30. |
|
|
