| 1. |
- Darelius, A, et al.
(författare)
-
Efficacy of salpingectomy at hysterectomy to reduce the risk of epithelial ovarian cancer: a systematic review.
- 2017
-
Ingår i: BJOG : an international journal of obstetrics and gynaecology. - 1471-0528 .- 1471-0528. ; 124:6, s. 880-889
-
Forskningsöversikt (refereegranskat)abstract
- It has been argued that salpingectomy would reduce the risk of epithelial ovarian cancer (EOC), based on the theory of the tube being the site of origin.To conduct a systematic review of 'salpingectomy' associated with ovarian cancer risk and 'salpingectomy with concomitant hysterectomy' on outcomes of complications including endocrine function.A comprehensive search was conducted in PubMed, Embase, and the Cochrane library.Original studies and systematic reviews were eligible.Each article was quality assessed. Data were extracted and, when possible, pooled in meta-analyses. The certainty of evidence across studies was evaluated using GRADE.Of 844 articles found, 11 were included. No study evaluated risk reduction for EOC after salpingectomy in conjunction with hysterectomy. Two retrospective studies reported a reduced ovarian cancer risk after indicated salpingectomy, compared with no surgery: adjusted hazard ratio 0.65 (95% confidence interval, 95% CI 0.52-0.81) and adjusted odds ratio 0.58 (95% CI 0.36-0.95). Complications did not differ between groups with or without salpingectomy, but were non-systematically reported. Ovarian endocrine function, measured with surrogate outcomes, did not differ at short-term follow-up in randomised or observational studies. The certainty of evidence was very low or low for all outcomes.There is currently insufficient evidence to state that opportunistic salpingectomy reduces the risk of EOC. The impact on long-term endocrine function is unknown. The heterogeneity in results and identified knowledge gaps stress the need for a prospective trial.Insufficient evidence for prophylactic removal of the fallopian tubes for risk reduction of ovarian cancer.
|
|
| 2. |
- Darelius, Anna, et al.
(författare)
-
Risk of epithelial ovarian cancer Type I and II after hysterectomy, salpingectomy and tubal ligation-A nationwide case-control study
- 2021
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 149:8, s. 1544-1552
-
Tidskriftsartikel (refereegranskat)abstract
- The proposed different origins and pathways to of the dualistic model of epithelial ovarian cancer (EOC) may affect and alter the potential risk reduction related to hysterectomy, salpingectomy and tubal ligation. The aim of our study was to analyze associations between hysterectomy, salpingectomy or tubal ligation and risk reduction of EOC Type I and II. In this nationwide register-based case-control study, women diagnosed with EOC, Fallopian tube or primary peritoneal cancer between 2008 and 2014 were included. Cases were classified into Type I and II according to histology and predefined criteria. The exposure variables: hysterectomy, salpingectomy and tubal ligation were identified from national registries. Conditional logistic regression analyses were performed to evaluate associations between Type I and II EOC and the exposure variables. Among 4669 registered cases, 4040 were eligible and assessed for subtyping resulting in 1033 Type I and 3007 Type II. Ten controls were randomly assigned to each case from the register of population. In regression analyses, women with previous salpingectomy had a significantly lower risk of EOC Type II (odds ratio [OR] 0.62; 95% confidence interval [95%CI] 0.45-0.85) but not Type I (OR 1.16; 95%CI 0.75-1.78). Hysterectomy was associated with a reduced risk of both EOC Type I (OR 0.71; 95%CI 0.52-0.99) and Type II (OR 0.81; 95%CI 0.68-0.96). Similar estimates were obtained for tubal ligation, although without statistical significance. The association between salpingectomy and reduced risk of EOC Type II supports the proposed theory of high-grade serous cancer originating from the tubal fimbriae.
|
|
| 3. |
- Jain, S., et al.
(författare)
-
Diagnostic potential of nanoparticle aided assays for MUC16 and MUC1 glycovariants in ovarian cancer
- 2022
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 151:7, s. 1175-1184
-
Tidskriftsartikel (refereegranskat)abstract
- Our study reports the discovery and evaluation of nanoparticle aided sensitive assays for glycovariants of MUC16 and MUC1 in a unique collection of paired ovarian cyst fluids and serum samples obtained at or prior to surgery for ovarian carcinoma suspicion. Selected glycovariants and the immunoassays for CA125, CA15-3 and HE4 were compared and validated in 347 cyst fluid and serum samples. Whereas CA125 and CA15-3 performed poorly in cyst fluid to separate carcinoma and controls, four glycovariants including MUC16(MGL), MUC16(STn), MUC1(STn) and MUC1(Tn) provided highly improved separations. In serum, the two STn glycovariants outperformed conventional CA125, CA15-3 and HE4 assays in all subcategories analyzed with main benefits obtained at high specificities and at postmenopausal and early-stage disease. Serum MUC16(STn) performed best at high specificity (90%-99%), but sensitivity was also improved by the other glycovariants and CA15-3. The highly improved specificity, excellent analytical sensitivity and robustness of the nanoparticle assisted glycovariant assays carry great promise for improved identification and early detection of ovarian carcinoma in routine differential diagnostics.
|
|
| 4. |
|
|
| 5. |
- Kristjansdottir, Björg, et al.
(författare)
-
Diagnostic performance of the biomarkers HE4 and CA125 in type I and type II epithelial ovarian cancer.
- 2013
-
Ingår i: Gynecologic oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 131:1, s. 52-58
-
Tidskriftsartikel (refereegranskat)abstract
- To evaluate the diagnostic performance of HE4 and CA125 in patients presenting with suspicious malignant ovarian cysts. We especially wanted to investigate the levels of HE4 and CA125 with regard to the gene and histology-unifying model of type I and type II epithelial ovarian cancer (EOC).
|
|
| 6. |
- Kristjansdottir, Björg
(författare)
-
Early Diagnosis of Epithelial Ovarian Cancer - Analysis of Novel Biomarkers
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Early Diagnosis of Epithelial Ovarian Cancer - Analysis of Novel Biomarkers Björg Kristjánsdóttir Department of Obstetrics & Gynecology, Institute of Clinical Sciences at Sahlgrenska Academy, University of Gothenburg, Sweden ABSTRACT Background: Majority of epithelial ovarian cancer (EOC) is detected in advanced stage with bad prognosis and high mortality. Reliable diagnostic markers are lacking, pre-cancerous lesions in the more aggressive tumors are not clearly defined, vague or unspecific early symptoms, and the localization of the ovaries, deep in the pelvis contributes to late diagnose. Heterogeneity, not only different type of histology, but also different intrinsic biology and behavior characterizes ovarian cancer. Invasive surgery with histological examination is needed to confirm the diagnosis. Less than 25% EOC are diagnosed early, when there is great possibility to cure and 5-year survival >90%, in contrast to 20-30% 5-year survival in late stage EOC. Thus, early detection is of utmost importance. Proximal fluids, like ovarian cyst fluid, are promising in the search for early markers. Cancer antigen 125 (CA125), the most used biomarker since 30 years, and a promising marker human epididymis 4 (HE4) have recently been approved by FDA to be used in the prediction of malignancy in women with a pelvic mass. Aims: To explore ovarian cyst fluid as a source mining for new diagnostic biomarkers for EOC, and to validate the markers found together with CA125 (Paper I-III); and to evaluate the diagnostic performance of HE4 and CA125, to distinguish between benign cysts and EOC, and EOC divided into slow growing type I and the aggressive type II EOC (Paper IV-V). Method: Cross sectional, observational, explorative, and diagnostic clinical studies, with prospective and consecutive collection of cystic fluid, blood and tumor tissue at the time of operation and retrospective analysis. Women with suspicious malignant pelvic cysts, already scheduled for operation at our clinic for tumor surgery were included. High throughput proteomic analyses were used for searching for novel markers, and selected proteins were validated with ELISA or immunoblot. Paper I: The cyst fluid proteome was mined with surfaceenhanced laser desorption/ionization time of flight (SELDI-TOF) mass spectrometry (MS) (n=192). Paper II: Enrichment of a selection of known cancer antigens to overcome high abundant proteins, and with focus on inflammation, was followed by Immunoprecipitation MS (n=38). Significantly differently expressed chemokines were validated (n=256). Paper III: Serous cystadenoma (n=5) and serous adenocarcinoma (n=10) of different stages were analyzed with isobaric tag for relative and absolute quantification (iTRAQ), followed by immunoblot validation (n=68). Paper IV-V: HE4 and CA125 levels in plasma were analyzed with ELISA and Risk of Ovarian Malignancy Algorithm (ROMA) was calculated (n=393). Significant differences, receiver operator characteristics (ROC) area under the curve (AUC), cut-off levels, sensitivity and specificity were estimated with regard to malignancy, grade, stage histologic subtype and type I and type II. Results: Paper I: Combination of Apolipoprotein CIII and Protein C inhibitor had the best AUC (0.91) in cyst fluid, and improved by CA125 (0.94). Abundant proteins were a problem in the cyst fluid analyses. Paper II: Interleukin-8 and Chemoattractant Protein-I were highly significantly increased expressed in cyst fluid. Increased inflammatory response was present in early tumor development and earlier than in blood. Paper III: Two of 87 differentially expressed proteins in cyst fluid, with high significance and fold change, Serum Amyloid A-4 (SAA4) and astacin-like metalloendopeptidase (ASTL) were validated, and SAA4 was significantly increased in cyst fluid, but not in blood. Paper IV: HE4 complemented CA125 in the diagnosis of ovarian cysts, especially in the premenopausal women. Sensitivity for ROMA at set specificity of 75% was highest in the postmenopausal cohort (87%). Paper V: HE4 and CA125 diagnosed the aggressive type II EOC most correctly (AUC 0.93), but the results were not acceptable in early stage type II (AUC 0.85) or in type I EOC (AUC 0.79) respective early type I AUC 0.73). Conclusion: Ovarian cyst fluid is an excellent source for the search of novel biomarkers for early diagnosis of EOC. Early events are found near the tumor in the early phase, like the inflammatory response and later on in the peripheral circulation. HE4 complements CA125 in predicting malignancy in cystic ovarian tumors. The result from this thesis support, that EOC should be looked upon as several different diseases. Finding early markers that are specific for each histology subgroup will be the future challenge. Combination of such markers in a panel could improve the early diagnosis of EOC.
|
|
| 7. |
- Kristjansdottir, Björg, et al.
(författare)
-
Early inflammatory response in epithelial ovarian tumor cyst fluids.
- 2014
-
Ingår i: Cancer medicine. - : Wiley. - 2045-7634. ; 3:5, s. 1302-1312
-
Tidskriftsartikel (refereegranskat)abstract
- Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P<0.0001) higher in the malignant (n=16) versus benign (n=22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n=256) and corresponding serum (n=256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P<0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P<0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors.
|
|
| 8. |
- Kristjansdottir, Björg, et al.
(författare)
-
Ovarian cyst fluid is a rich proteome resource for detection of new tumor biomarkers.
- 2012
-
Ingår i: Clinical proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 9:14
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: We aimed to investigate the use of ovarian cyst fluid as a source for biomarker discovery and to find novel biomarkers for use in the diagnosis of epithelial ovarian tumors. RESULTS: Ovarian cyst fluids from 218 women were collected and 192 (benign n = 129, malignant n = 63) were analyzed using mass spectrometry. 1180 peaks were detected, 221 of which were differently expressed between benign and malignant ovarian tumors. Seventeen peaks had receiver operating curve and area under the curve values >0.70; the majority of these represented peaks for apolipoproteins C-III and C-I (ApoC-I), transthyretin (TTR), serum amyloid A4 (SAA4), and protein C inhibitor (PCI). ApoC-III, PCI, and serum CA125, with an ROC AUC 0.94 was the best combination for diagnosing epithelial ovarian cancer. ApoC-III and PCI was analyzed with ELISA in the original cohort (n = 40) and in 40 new cyst fluid samples for confirmation with an independent method and validation. Results from MS and ELISA for ApoC-III correlated well (p = 0.04). In the validation set, ApoC-III was significantly (p = 0.001) increased in the malignant epithelial ovarian cancers. CONCLUSIONS: Fluid from ovarian cysts connected directly to the primary tumor harbor many possible new tumor-specific biomarkers. Biomarkers found in ovarian cyst fluid may be used as molecular imaging targets for early diagnostics and prediction of therapy. Plasma abundant proteins are also influencing the cystic fluid proteome. Methods for isolating less frequent cyst fluid proteins are needed.
|
|
| 9. |
- Kristjansdottir, Björg, et al.
(författare)
-
Potential tumor biomarkers identified in ovarian cyst fluid by quantitative proteomic analysis, iTRAQ.
- 2013
-
Ingår i: Clinical proteomics. - : Springer Science and Business Media LLC. - 1542-6416 .- 1559-0275. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- Epithelial-derived ovarian adenocarcinoma (EOC) is the most deadly gynecologic tumor, and the principle cause of the poor survival rate is diagnosis at a late stage. Screening and diagnostic biomarkers with acceptable specificity and sensitivity are lacking. Ovarian cyst fluid should harbor early ovarian cancer biomarkers because of its closeness to the tumor. We investigated ovarian cyst fluid as a source for discovering biomarkers for use in the diagnosis of EOC.
|
|
| 10. |
- Liljedahl, Leena, et al.
(författare)
-
Targeted Selected Reaction Monitoring Verifies Histology Specific Peptide Signatures in Epithelial Ovarian Cancer
- 2021
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:22
-
Tidskriftsartikel (refereegranskat)abstract
- Simple SummaryOvarian cancer is a lethal disease due to its late phase discovery. Any steps towards improving early diagnostics will dramatically increase survival rates. To identify new ovarian cancer biomarker panels, we need to focus on early-stage disease and all histologic subtypes. In this study we have, based on prior discoveries, constructed a multiplexed targeted selected-reaction-monitoring assay to detect peptides from 177 proteins in only 20 mu L of plasma. The assay was evaluated in patients with a focus on early-stages and all ovarian cancer histologies in separate groups. With multivariate analysis, we found the highest predictive value in the benign vs. low-grade serous (Q2 = 0.615) and mucinous (Q2 = 0.611) early stage compared to all malignant (Q2 = 0.226) or late stage (Q2 = 0.43) ovarian cancers. The results show that each ovarian cancer histology subgroup can be identified by a unique panel of proteins.Epithelial ovarian cancer (OC) is a disease with high mortality due to vague early clinical symptoms. Benign ovarian cysts are common and accurate diagnosis remains a challenge because of the molecular heterogeneity of OC. We set out to investigate whether the disease diversity seen in ovarian cyst fluids and tumor tissue could be detected in plasma. Using existing mass spectrometry (MS)-based proteomics data, we constructed a selected reaction monitoring (SRM) assay targeting peptides from 177 cancer-related and classical proteins associated with OC. Plasma from benign, borderline, and malignant ovarian tumors were used to verify expression (n = 74). Unsupervised and supervised multivariate analyses were used for comparisons. The peptide signatures revealed by the supervised multivariate analysis contained 55 to 77 peptides each. The predictive (Q2) values were higher for benign vs. low-grade serous Q2 = 0.615, mucinous Q2 = 0.611, endometrioid Q2 = 0.428 and high-grade serous Q2 = 0.375 (stage I-II Q2 = 0.515; stage III Q2 = 0.43) OC compared to benign vs. all malignant Q2 = 0.226. With targeted SRM MS we constructed a multiplexed assay for simultaneous detection and relative quantification of 185 peptides from 177 proteins in only 20 mu L of plasma. With the approach of histology-specific peptide patterns, derived from pre-selected proteins, we may be able to detect not only high-grade serous OC but also the less common OC subtypes.
|
|
| 11. |
- Lycke, Maria, et al.
(författare)
-
A multicenter clinical trial validating the performance of HE4, CA125, risk of ovarian malignancy algorithm and risk of malignancy index
- 2018
-
Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258. ; 151:1, s. 159-165
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To validate, in a multicenter clinical trial, the performance of biomarkers and algorithms for differential diagnosis in a population of women diagnosed with an unknown ovarian cyst or pelvic tumor. Methods. Six hospitals in Western Sweden consecutively enrolled 638 women from September 2013 to February 2016. Serum, transvaginal ultrasound data, and basic patient characteristics were collected preoperatively. Biomarker levels, risk of malignancy algorithm (ROMA), and risk of malignancy index (RMI) were calculated and compared with the final pathology report. Results. Our sample of 638 patients had 445 benign, 31 borderline, and 162 malignant tumors recorded, and the overall incidence of epithelial ovarian cancer was 21%. In postmenopausal women, RMI (>200), ROMA (>= 29.9), CA125 (>35 U/mL), and HE4 (>140 pmol/L) showed sensitivity at 89%, 91%, 92%, and 72%, respectively, and specificity at 80%, 77%, 80%, and 92%. In premenopausal women, sensitivity of RMI, ROMA (>= 11.6), CA125, and HE4 (>70 pmol/L) was 87%, 87%, 96%, and 83%, respectively, and specificity was 90%, 81%, 60%, 91%. Diagnostic accuracy (ROC AUC) of RMI and ROMA in postmenopausal women was 0.85 and 0.84, and in premenopausal women, 0.90 and 0.81. Conclusion. Our results suggest that CA125 is superior to HE4 as a biomarker to identify women with ovarian cancer. HE4 more correctly identifies benign lesions, which may help in differential diagnoses to guide the level of care and decrease overtreatment. This study confirms prior results from single-center studies and suggests the implementation of HE4 measurement in daily practice. (C) 2018 Elsevier Inc. All rights reserved.
|
|
| 12. |
- Lycke, Maria, et al.
(författare)
-
Consideration should be given to smoking, endometriosis, renal function (eGFR) and age when interpreting CA125 and HE4 in ovarian tumor diagnostics
- 2021
-
Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 59:12, s. 1954-1962
-
Tidskriftsartikel (refereegranskat)abstract
- To evaluate the impact of different biologic, histopathologic and lifestyle factors on serum levels of human epididymis protein 4 (HE4) and Cancer antigen 125 (CA125) in the diagnostic work up of women with an ovarian cyst or pelvic tumor. The statistical evaluation was performed on a population of 445 women diagnosed with a benign ovarian disease, included in a large Swedish multicenter trial (ClinicalTrials.gov NCT03193671). Multivariable logistic regression analyses were performed to distinguish between the true negatives and false positives through adjusting for biologic, histopathologic and lifestyle factors on serum samples of CA125 and HE4 separately. The likelihood ratio test was used to determine statistical significance and Benjamini-Hochberg correction to adjust for multiple testing. A total of 31% of the women had false positive CA125 but only 9% had false positive results of HE4. Smoking (OR 6.62 95% CI 2.93-15.12) and impaired renal function, measured by eGFR (OR 0.18 95% CI 0.08-0.39), were independently predictive of falsely elevated serum levels of HE4. Endometriosis was the only variable predictive of falsely elevated serum levels of CA125 (OR 7.96 95% CI 4.53-14.39). Age correlated with increased serum levels of HE4. Smoking, renal failure, age and endometriosis are factors that independently should be considered when assessing serum levels of HE4 and CA125 in women with an ovarian cyst or pelvic mass to avoid false indications of malignant disease.
|
|
| 13. |
- Lycke, Maria, et al.
(författare)
-
Increased Diagnostic Accuracy of Adnexal Tumors with A Combination of Established Algorithms and Biomarkers
- 2020
-
Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 9:2
-
Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is the most lethal gynecologic cancer. Pre-diagnostic testing lacks sensitivity and specificity, and surgery is often the only way to secure the diagnosis. Exploring new biomarkers is of great importance, but the rationale of combining validated well-established biomarkers and algorithms could be a more effective way forward. We hypothesized that we can improve differential diagnostics and reduce false positives by combining (a) risk of malignancy index (RMI) with serum HE4, (b) risk of ovarian malignancy algorithm (ROMA) with a transvaginal ultrasound score or (c) adding HE4 to CA125 in a simple algorithm. With logistic regression modeling, new algorithms were explored and validated using leave-one-out cross validation. The analyses were performed in an existing cohort prospectively collected prior to surgery, 2013-2016. A total of 445 benign tumors and 135 ovarian cancers were included. All presented models improved specificity at cut-off compared to the original algorithm, and goodness of fit was significant (p < 0.001). Our findings confirm that HE4 is a marker that improves specificity without hampering sensitivity or diagnostic accuracy in adnexal tumors. We provide in this study "easy-to-use" algorithms that could aid in the triage of women to the most appropriate level of care when presenting with an unknown ovarian cyst or suspicious ovarian cancer.
|
|
| 14. |
- Marcisauskas, Simonas, 1988, et al.
(författare)
-
Univariate and classification analysis reveals potential diagnostic biomarkers for early stage ovarian cancer Type 1 and Type 2
- 2019
-
Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 196, s. 57-68
-
Tidskriftsartikel (refereegranskat)abstract
- Biomarkers for early detection of ovarian tumors are urgently needed. Tumors of the ovary grow within cysts and most are benign. Surgical sampling is the only way to ensure accurate diagnosis, but often leads to morbidity and loss of female hormones. The present study explored the deep proteome in well-defined sets of ovarian tumors, FIGO stage I, Type 1 (low-grade serous, mucinous, endometrioid; n = 9), Type 2 (high-grade serous; n = 9), and benign serous (n = 9) using TMT–LC–MS/MS. Data are available via ProteomeXchange with identifier PXD010939. We evaluated new bioinformatics tools in the discovery phase. This innovative selection process involved different normalizations, a combination of univariate statistics, and logistic model tree and naive Bayes tree classifiers. We identified 142 proteins by this combined approach. One biomarker panel and nine individual proteins were verified in cyst fluid and serum: transaldolase-1, fructose-bisphosphate aldolase A (ALDOA), transketolase, ceruloplasmin, mesothelin, clusterin, tenascin-XB, laminin subunit gamma-1, and mucin-16. Six of the proteins were found significant (p <.05) in cyst fluid while ALDOA was the only protein significant in serum. The biomarker panel achieved ROC AUC 0.96 and 0.57 respectively. We conclude that classification algorithms complement traditional statistical methods by selecting combinations that may be missed by standard univariate tests. Significance: In the discovery phase, we performed deep proteome analyses of well-defined histology subgroups of ovarian tumor cyst fluids, highly specified for stage and type (histology and grade). We present an original approach to selecting candidate biomarkers combining several normalization strategies, univariate statistics, and machine learning algorithms. The results from validation of selected proteins strengthen our prior proteomic and genomic data suggesting that cyst fluids are better than sera in early stage ovarian cancer diagnostics.
|
|
| 15. |
- Mateoiu, Constantina, et al.
(författare)
-
Analysis of blood group antigens on MUC5AC in mucinous ovarian cancer tissues using in situ proximity ligation assay.
- 2021
-
Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 31:11, s. 1464-1471
-
Tidskriftsartikel (refereegranskat)abstract
- MUC5AC has been indicated to be a marker for mucinous ovarian cancer (OC). We investigated the use of in situ proximity ligation assay (PLA) for blood group ABH expressing MUC5AC to differentiate between serous and mucinous OC, to validate preceding observations that also MUC5AC ABH expression is increased in mucinous OC. We developed PLA for anti-A, B, and H/anti-MUC5AC and a PLA using a combined lectin Ulex europaeus agglutinin I (UEA I)/anti-MUC5AC assay. The PLAs were verified with mass spectrometry, where mucinous OC secretor positive patients' cysts fluids containing ABH O-linked oligosaccharides also showed positive OC tissue PLA staining. A nonsecretor mucinous OC cyst fluid was negative for ABH and displayed negative PLA staining of the matched tissue. Using the UEA I/MUC5AC PLA, we screened a tissue micro array of 410 ovarian tissue samples from patients with various stages of mucinous or serous OC, 32 samples with metastasis to the ovaries and 34 controls. The PLA allowed differentiating mucinous tumors with a sensitivity of 84% and a specificity of 97% both against serous cancer but also compared to tissues from controls. This sensitivity is close to the expected incidence of secretor individuals in a population. The recorded sensitivity was also found to be higher compared to mucinous type cancer with metastasis to the ovaries, where only 32% were positive. We conclude that UEA 1/MUC5AC PLA allows glycospecific differentiation between serous and mucinous OC in patients with positive secretor status and will not identify secretor negative individuals with mucinous OC.
|
|
| 16. |
- Meagher, N. S., et al.
(författare)
-
A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases
- 2019
-
Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 32, s. 1834-1846
-
Tidskriftsartikel (refereegranskat)abstract
- Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7−/CK20+/CDX2+/PAX8−. This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1–50% of tumor cells) and diffuse (>50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker indistinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice. © 2019, The Author(s), under exclusive licensc to United States & Canadian Academy of Pathology.
|
|
| 17. |
- Partheen, Karolina, 1976, et al.
(författare)
-
Evaluation of ovarian cancer biomarkers HE4 and CA-125 in women presenting with a suspicious cystic ovarian mass.
- 2011
-
Ingår i: Journal of gynecologic oncology. - : Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology and Colposcopy. - 2005-0399 .- 2005-0380. ; 22:4, s. 244-52
-
Tidskriftsartikel (refereegranskat)abstract
- Women presenting with a large or complex ovarian cyst are referred to extensive surgical staging to ensure the correct diagnosis and treatment of a possible epithelial ovarian cancer. We hypothesized that measurement of the biomarkers HE4 and CA-125 preoperatively would improve the assignment of these patients to the correct level of care.
|
|
| 18. |
- Wang, Y. X., et al.
(författare)
-
Diagnostic potential of tumor DNA from ovarian cyst fluid
- 2016
-
Ingår i: Elife. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids. Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers. In contrast, no mutations were found in the cyst fluids of 18 patients with benign tumors or nonneoplastic cysts. Though large, prospective studies are needed to demonstrate the safety and clinical utility of this approach, our results suggest that the genetic evaluation of cyst fluids might be able to inform the management of the large number of women with these lesions.
|
|
