| 1. |
- Arildsen, Nicolai Skovbjerg, et al.
(författare)
-
Detecting TP53 mutations in diagnostic and archival liquid-based Pap samples from ovarian cancer patients using an ultra-sensitive ddPCR method
- 2019
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 1-8
-
Tidskriftsartikel (refereegranskat)abstract
- High-grade serous ovarian cancer (HGSOC) is the most common subtype of epithelial ovarian cancer and early detection is challenging. TP53 mutations are a hallmark of HGSOC and detection of these mutations in liquid-based Pap samples could provide a method for early diagnosis. Here we evaluate the use of IBSAFE, an ultra-sensitive droplet digital PCR (ddPCR) method, for detecting TP53 mutations in liquid-based Pap samples collected from fifteen women at the time of diagnosis (diagnostic samples) and/or up to seven years prior to diagnosis (archival samples). We analysed tumours for somatic TP53 mutations with next generation sequencing and were able to detect the corresponding mutations in diagnostic samples from six of eight women, while one patient harboured a germline mutation. We further detected a mutation in an archival sample obtained 20 months prior to the ovarian cancer diagnosis. The custom designed IBSAFE assays detected minor allele frequencies (MAFs) with very high assay sensitivity (MAF = 0.0068%) and were successful despite low DNA abundance (0.17-206.14 ng, median: 17.27 ng). These results provide support for further evaluation of archival liquid-based Pap samples for diagnostic purposes and demonstrate that ultra-sensitive ddPCR should be evaluated for ovarian cancer screening in high-risk groups or in the recurrent setting.
|
|
| 2. |
- Asp, Mihaela, et al.
(författare)
-
Ovarian tumor frozen section, a multidisciplinary affair
- 2022
-
Ingår i: Acta Oncologica. - 1651-226X. ; 61:7, s. 785-792
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundOvarian Cancer (OC) constitute the eighth most common cancers among women worldwide. Surgery remains the cornerstone in the management of OC. Intraoperative frozen section (FS) diagnosis is widely used to decide the surgery course. We aimed to assess the reliability of intraoperative FS diagnosis for treatment planning of patients with suspected OC from a multidisciplinary perspective. The clinical consequences of reclassification and the multidisciplinary management of the therapy plan, is the secondary aim of this study. To our knowledge, this information is sparely investigated.MethodsA single-center, retrospective population-based study of patients who underwent surgery for suspected OC between 2018 and 2020. Histopathological outcomes were classified as benign, borderline, or malignant. The FS diagnosis was the diagnostic test, and the final histopathology report was the gold standard. Diagnostic capability for treatment planning was assessed, and modifications made possible by overall clinical knowledge were discussed.ResultsA total of 358 patients were identified, of whom 187 were included in the FS group. Overall accuracy was 89.8%, and 19 patients were reclassified; the malignancy grade of 15 tumors was underestimated. Prevalence, sensitivity, specificity, positive predictive value, and negative predictive value for invasive malignancies on FS were 54.0% (CI 46.6–61.3%), 88.1% (CI 80.2–93.7%), 98.8% (CI 93.7–99.9%), 98.9% (CI 92.7–99.8%), and 87.6% (CI 80.6–92.4%), respectively. Tumors incorrectly graded by FS tended to be of borderline-related.ConclusionsThe reliability of the FS methodology was an accurate test to help perform appropriate surgery and plan swift oncological treatment. FS is a reliable method to diagnose invasive malignancies and benign pathology. The communication between the pathologist, surgeon, and medical oncologist is highly important for both intraoperative decision-making and postoperative patient care.
|
|
| 3. |
- Asp, Mihaela, et al.
(författare)
-
Prognostic Value of Peritoneal Cancer Index After Complete Cytoreductive Surgery in Advanced Ovarian Cancer
- 2022
-
Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 1791-7530 .- 0250-7005. ; 42:5, s. 2541-2551
-
Tidskriftsartikel (refereegranskat)abstract
- Background/aim: Residual disease (RD) after primary debulking surgery (PDS) is a prognostic factor for survival in advanced ovarian cancer (AOC). This study aimed to examine whether the tumor extent affects overall survival (OS) and progression-free survival (PFS) in AOC patients treated with PDS.Patients and methods: A total of 118 patients treated with PDS were included. Age, ECOG score, AOC International Federation of Gynecology and Obstetrics (FIGO) stage, CA-125, RD, peritoneal cancer index (PCI), preoperative imaging (CT-PCI) and macroscopic visualization at the surgery start (S-PCI) were analyzed. Tumor extent was quantified using the PCI, and by CT-PCI and S-PCI. Cox regression, Kaplan-Meier and receiver operating curves (ROC) were performed for survival analyses.Results: S-PCI correlated with both OS (1.067, 95%CI=1.018-1.119, p<0.007) and PFS. Patients exhibiting S-PCI≥18.5, adjusted to age, performance status, and RD, had a two-fold risk of dying (HR=2.070, 95%CI=1.061-4.038, p=0.033) compared those with PCI<18.5. CT-PCI correlated with OS in crude data (1.037, 95%CI=1.005-1.071, p=0.025), but this was not sustained in multivariate analyses. RD of any size doubled the risk of dying (2.177, 95%CI=1.235-3.838, p=0.007).Conclusion: The tumor extent at the beginning of surgery seemed to affect OS in patients with AOC, regardless of the extent of RD at the end of the surgery. PCI above 18.5 doubled the risk of dying of the disease. No difference in major complications was noted in the two groups of patients. CT-PCI seemed to play a prognostic role for PFS; however, it is still to be investigated as a prognostic factor for OS.
|
|
| 4. |
- Asp, Mihaela, et al.
(författare)
-
The role of computed tomography in the assessment of tumour extent and the risk of residual disease after upfront surgery in advanced ovarian cancer (AOC)
- 2022
-
Ingår i: Archives of Gynecology and Obstetrics. - : Springer Science and Business Media LLC. - 1432-0711.
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeEpithelial ovarian cancer is usually diagnosed in the advanced stages. To choose the best therapeutic approach, an accurate preoperative assessment of the tumour extent is crucial. This study aimed to determine whether the peritoneal cancer index (PCI), the amount of ascites, and the presence of cardiophrenic nodes (CPLNs) visualized by computed tomography (CT) can assess the tumour extent (S-PCI) and residual disease (RD) for advanced ovarian cancer (AOC) patients treated with upfront surgery.MethodsIn total, 118 AOC cases were included between January 2016 and December 2018 at Skåne University Hospital, Lund, Sweden. Linear regression and interclass correlation (ICC) analyses were used to determine the relationship between CT-PCI and S-PCI. The patients were stratified in complete cytoreductive surgery (CCS) with no RD or to non-CCS with RD of any size. The amount of ascites on CT (CT-ascites), CA-125 and the presence of radiological enlarged CPLNs (CT-CPLN) were analysed to evaluate their impact on estimating RD.ResultsCT-PCI correlated well with S-PCI (0.397; 95% CI 0.252–0.541; p < 0.001). The risk of RD was also related to CT-PCI (OR 1.069 (1.009–1.131), p < 0.023) with a cut-off of 21 for CT-PCI (0.715, p = 0.000). The sensitivity, specificity, positive predictive value and negative predictive value were 58.5, 70.3, 52.2 and 75.4%, respectively. CT-ascites above 1000 ml predicted RD (OR 3.510 (1.298–9.491) p < 0.013).ConclusionCT is a reliable tool to assess the extent of the disease in advanced ovarian cancer. Higher CT-PCI scores and large volumes of ascites estimated on CT predicted RD of any size.
|
|
| 5. |
- Asp, Mihaela, et al.
(författare)
-
Tru-Cut Biopsy in Gynecological Cancer: Adequacy, Accuracy, Safety and Clinical Applicability
- 2023
-
Ingår i: Journal of Multidisciplinary Healthcare. - 1178-2390. ; 16, s. 1367-1377
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Tru-cut biopsy is a minimally invasive technique used to obtain tissue samples for the diagnosis of tumors, especially in patients where primary surgery is not indicated. The aim of this study was to assess the adequacy, accuracy and safety of the tru-cut biopsy for diagnosis in gynecological cancer.Methods: A retrospective population-based review of 328 biopsies was conducted. The indications for tru-cut biopsies were diagnosis of primary tumors, metastases of gynecological and non-gynecological tumors, and suspected recurrences. A tissue sample was considered adequate when the quality/quality was sufficient to identify the subtype/origin of the tumor. Potential factors affecting adequacy were analyzed using logistic regressions analyses. Accuracy was defined as agreement between the diagnosis of the tru-cut biopsy and the postoperative histology. The therapy plan was registered, and the clinical applicability of the tru-cut biopsy was investigated. Complications within 30 days after the biopsy procedure were registered.Results: In total, 300 biopsies were identified as tru-cut biopsies. The overall adequacy was 86.3%, varying between 80.8% and 93.5%, respectively, when performed by a gynecological oncologist or a gynecologist with a subspecialty in ultrasound diagnosis. Sampling of a pelvic mass had a lower adequacy (81.6%) compared with sampling of the omentum (93.9%) or carcinomatosis (91.5%). The accuracy was 97.5%, and the complication rate was 1.3%.Conclusion: The tru-cut biopsy is a safe and reliable diagnostic method with a high accuracy and a good adequacy, depending on the site of the tissue sample, indications for the biopsy and the experience of the operator.
|
|
| 6. |
- Bååth, Maria, et al.
(författare)
-
MET Expression and Cancer Stem Cell Networks Impact Outcome in High-Grade Serous Ovarian Cancer
- 2021
-
Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 12:5
-
Tidskriftsartikel (refereegranskat)abstract
- Overexpression of the receptor tyrosine kinase MET has been linked to poor survival in several cancer types, and MET has been suggested to interact with stem cell networks. In vitro studies have further suggested a possible benefit of a combined treatment using PARP and MET inhibitors. We used a tissue microarray (TMA) with 130 samples of advanced-stage high-grade serous fallopian tube/ovarian cancer (HGSC) to investigate the prognostic value of MET protein expression alone and in combination with the stem cell factor SOX2. The possible synergistic effects of a PARP and MET inhibitor treatment were evaluated in two cell lines with BRCA1 or BRCA2 deficiency and in their BRCA1/2-proficient counterparts. Patients with tumors positive for MET had worse overall survival (log-rank test, p = 0.015) compared to patients with MET-negative tumors. The prognostic role of MET was even more prominent in the subgroup of patients with SOX2-negative tumors (p = 0.0081). No synergistic effects of the combined treatment with PARP and MET inhibitors were found in the cell lines examined. We conclude that MET expression could be used as a marker for OS in HGSC and that stemness should be taken into consideration when evaluating the mechanisms of this effect.
|
|
| 7. |
- Bååth, Maria, et al.
(författare)
-
SOX2 is a promising predictor of relapse and death in advanced stage high-grade serous ovarian cancer patients with residual disease after debulking surgery
- 2020
-
Ingår i: Molecular and Cellular Oncology. - : Informa UK Limited. - 2372-3556. ; 7:6
-
Tidskriftsartikel (refereegranskat)abstract
- The transcription factor SOX2 is a well-established and important stem cell marker. Its role in cancer biology remains unclear, but it has been proposed to also be a marker of cancer stem cells. We investigated the role of SOX2 protein expression in women with high-grade serous ovarian cancer (HGSOC) to determine its potential prognostic and treatment predictive value. We constructed a tissue microarray of 130 advanced stage HGSOC tumors with an average of 6 cores each, stained for SOX2 protein expression and evaluated survival outcomes. We also treated two HGSOC cell lines with carboplatin and paclitaxel and measured SOX2 expression by RT-PCR and immunoblotting at different doses and time-points. Among patients with non-radical debulking surgery overall and progression-free survival were shorter for patients with SOX2 positive tumors (mean 26 vs. 39 months, log-rank test: p = .0076, and mean 14 vs. 19 months, p = .055, respectively). Knockdown of SOX2 in cell lines did not affect growth inhibition following chemotherapy treatment. Our results show that SOX2 has a strong prognostic potential among HGSOC patients with residual tumor tissue after debulking surgery and suggest that SOX2 expressing cells remaining after non-radical debulking surgery may constitute a subpopulation of cancer stem cells with greater tumor-initiating potential.
|
|
| 8. |
- Chang, Jing-Yu, et al.
(författare)
-
Serotonin uptake into cerebrovascular nerve fibers of rat, visualization by immunohistochemistry, disappearance following sympathectomy, and release during electrical stimulation
- 1989
-
Ingår i: Brain Research. - : Elsevier BV. - 1872-6240 .- 0006-8993. ; 492:1-2, s. 79-88
-
Tidskriftsartikel (refereegranskat)abstract
- Immunohistochemistry as well as in vitro uptake and release of [3H]5-HT were performed on pial arteries of rat to investigate the nature of 5-HT containing nerve fibers. Immunoreactive fibers were constantly found only in the basilar, vertebral and superior cerebellar arteries, while in the other parts of the circle of Willis, 5-HT immunofluorescent fibers were absent. After systemic treatment with tryptophan following inhibition of monoamine oxidase with nialamide the immunofluorescence intensity was markedly enhanced. The 5-HT immunoreactive fibers disappeared after superior cervical ganglionectomy or intraventricular administration of 6-hydroxydopamine, but persisted after administration of 5,6-dihydroxytryptamine. When isolated vessels were incubated in low concentration of 5-HT (1 nM) together with nialamide, a very dense plexus of 5-HT immunoreactive fibers appeared in all branches of the circle of Willis. Uptake and release experiments were carried out by incubation of arterial preparations with 3 nM [3H]5-HT (together with nialamide), followed by electrical field stimulation, or by exposure to tyramine or 124 mM potassium, all of which induced a 100%-350% increase in the tritium release over prestimulation values. Preincubation with cocaine and bilateral superior cervical ganglionectomy abolished or markedly attenuated the release upon all modes of stimulation. The results suggested that the 5-HT observed by immunohistochemistry in pial arteries is located in sympathetic nerve terminals where it may serve as a neuromodulator that is released during nerve activation.
|
|
| 9. |
|
|
| 10. |
|
|
