Surgical staging and prognosis in serous borderline ovarian tumours (BOT): a subanalysis of the AGO ROBOT study.
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ABSTRACT:
SUBMITTER: Trillsch F
PROVIDER: S-EPMC4333495 | biostudies-other | 2015 Feb
REPOSITORIES: biostudies-other
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Project description:ObjectiveTo determine changes in the characteristics of low-grade serous ovarian cancer (LGSOC) and serous borderline ovarian tumor (serous-BOT) in a time-specific manner.MethodsWe conducted a population-based retrospective study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2000. Trends, demographics, and outcomes of 775 women with well-differentiated serous ovarian cancer, used as a surrogate for LGSOC, were compared to 3937 women with serous-BOT.ResultsIn the multivariable analysis, women with LGSOC were more likely to be older, have stage II-IV disease, and have undergone hysterectomy at surgery, but less likely to be a Western U.S. resident compared to those with serous-BOT (all, adjusted-P < 0.05). During the study period, the number of LGSOCs decreased by 25.9%, particularly stage I disease (37.6% relative decrease) compared to stage II-IV disease (21.1% relative decrease) (all, P < 0.05). With a median follow-up of 16.9 years, there was a decreasing trend in the 15-year overall survival rates among LGSOC (28.7% relative decrease, P = 0.056) but not in serous-BOT (2.5% relative increase, P = 0.416) as a whole cohort. The magnitude of hazard risk from all-cause death for women with LGSOC compared to those with serous-BOT increased by 68.9% from 1988 to 2000 (P < 0.001). LGSOC remained an independent prognostic factor for decreased overall survival compared to serous-BOT (adjusted-P < 0.05).ConclusionOur study suggests that the decreasing number and survival of LGSOC over time may be due to a diagnosis-shift from LGSOC to serous-BOT. Given the distinct characteristics and outcomes of LGSOC compared to serous-BOT, our study endorses the importance of making the correct diagnosis upfront. Whether this diagnostic-shift supports a hypothesis that serous-BOT is a precursor lesion of LGSOC merits further investigation.
| S-EPMC7537352 | biostudies-literature
Project description:There is debate as to whether peritoneal implants associated with serous borderline tumours/atypical proliferative serous tumours (SBT/APSTs) of the ovary are derived from the primary ovarian tumour or arise independently in the peritoneum. We analysed 57 SBT/APSTs from 45 patients with advanced-stage disease identified from a nation-wide tumour registry in Denmark. Mutational analysis for hotspots in KRAS and BRAF was successful in 55 APSTs and demonstrated KRAS mutations in 34 (61.8%) and BRAF mutations in eight (14.5%). Mutational analysis was successful in 56 peritoneal implants and revealed KRAS mutations in 34 (60.7%) and BRAF mutations in seven (12.5%). Mutational analysis could not be performed in two primary tumours and in nine implants, either because DNA amplification failed or because there was insufficient tissue for mutational analysis. For these specimens we performed VE1 immunohistochemistry, which was shown to be a specific and sensitive surrogate marker for a V600E BRAF mutation. VE1 staining was positive in one of two APSTs and seven of nine implants. Thus, among 63 implants for which mutation status was known (either by direct mutational analysis or by VE1 immunohistochemistry), 34 (53.9%) had KRAS mutations and 14 (22%) had BRAF mutations, of which identical KRAS mutations were found in 34 (91%) of 37 SBT/APST-implant pairs and identical BRAF mutations in 14 (100%) of 14 SBT/APST-implant pairs. Wild-type KRAS and BRAF (at the loci investigated) were found in 11 (100%) of 11 SBT/APST-implant pairs. Overall concordance of KRAS and BRAF mutations was 95% in 59 of 62 SBT/APST-implant (non-invasive and invasive) pairs (p < 0.00001). This study provides cogent evidence that the vast majority of peritoneal implants, non-invasive and invasive, harbour the identical KRAS or BRAF mutations that are present in the associated SBT/APST, supporting the view that peritoneal implants are derived from the primary ovarian tumour.
| S-EPMC4086471 | biostudies-literature
Project description:To determine the oncological outcomes following fertility-sparing surgery (FSS) for the management of Borderline Ovarian Tumours (BOTs). A retrospective analysis of participants diagnosed with BOTs between January 2004 and December 2020 at the West London Gynaecological Oncology Centre was conducted. A total of 172 women were diagnosed; 52.3% (90/172) underwent FSS and 47.7% (82/172) non-FSS. The overall recurrence rate of disease was 16.9% (29/172), of which 79.3% (23/29) presented as the recurrence of serous or sero-mucinous BOTs and 20.7% (6/29) as low-grade serous carcinoma (LGSC). In the FSS group, the recurrence rate of BOTs was 25.6% (23/90) presenting a median 44.0 (interquartile range (IQR) 41.5) months, of which there were no episodes of recurrence presenting as LGSC reported. In the non-FSS group, all recurrences of disease presented as LGSC, with a rate of 7.7% (6/78), following a median of 47.5 months (IQR 47.8). A significant difference between the type of surgery performed (FSS v Non-FSS) and the association with recurrence of BOT was observed (Pearson Chi-Square: p = 0.000; x = 20.613). Twelve women underwent ultrasound-guided ovarian wedge resection (UGOWR) as a novel method of FSS. Recurrence of BOT was not significantly associated with the type of FSS performed (Pearson Chi- Square: x = 3.166, p = 0.379). Non-FSS is associated with negative oncological outcomes compared to FSS, as evidenced by the higher rate of recurrence of LGSC. This may be attributed to the indefinite long-term follow up with ultrasound surveillance all FSS women undergo, enabling earlier detection and treatment of recurrences.
| S-EPMC8946233 | biostudies-literature
Project description:Background: Changes in DNA methylation patterns are a pivotal mechanism of carcinogenesis. In some tumors, aberrant methylation precedes genetic changes, while gene expression may be more frequently modified due to methylation alterations than by mutations. Methods: Herein, 128 serous ovarian tumors were analyzed, including borderline ovarian tumors (BOTS) with (BOT.V600E) and without (BOT) the BRAF V600E mutation, low-grade (lg), and high-grade (hg) ovarian cancers (OvCa). The methylome of the samples was profiled with Infinium MethylationEPIC microarrays. Results: The biggest number of differentially methylated (DM) CpGs and regions (DMRs) was found between lgOvCa and hgOvCa. By contrast, the BOT.V600E tumors had the lowest number of DM CpGs and DMRs compared to all other groups and, in relation to BOT, their genome was strongly downmethylated. Remarkably, the ten most significant DMRs, discriminating BOT from lgOvCa, encompassed the MHC region on chromosome 6. We also identified hundreds of DMRs, being of potential use as predictive biomarkers in BOTS and hgOvCa. DMRs with the best discriminative capabilities overlapped the following genes: BAIAP3, IL34, WNT10A, NEU1, SLC44A4, and HMOX1, TCN2, PES1, RP1-56J10.8, ABR, NCAM1, RP11-629G13.1, AC006372.4, NPTXR in BOTS and hgOvCa, respectively. Conclusions: The global genome-wide hypomethylation positively correlates with the increasing aggressiveness of ovarian tumors. We also assume that the immune system may play a pivotal role in the transition from BOTS to lgOvCa. Given that the BOT.V600E tumors had the lowest number of DM CpGs and DMRs compared to all other groups, when methylome is considered, such tumors might be placed in-between BOT and OvCa.
2024-10-18 | GSE267068 | GEO
Project description:BackgroundSerous borderline ovarian tumor (SBOT) and high-grade serous ovarian cancer (HGSOC) are two distinct subtypes of epithelial ovarian tumors, with markedly different biologic background, behavior, prognosis, and treatment. However, the histologic diagnosis of serous ovarian tumors can be subjectively variable and labor-intensive as multiple tumor slides/blocks need to be thoroughly examined to search for these features.Materials and methodsWe developed a novel informatics system to facilitate objective and scalable diagnosis screening for SBOT and HGSOC. The system was built upon Groovy scripts and QuPath to enable interactive annotation and data exchange.ResultsThe system was used to successfully detect cellular boundaries and extract an expanded set of cellular features representing cell- and tissue-level characteristics. The performance of cell-level classification for both tumor and stroma cells achieved >90% accuracy. The performance of differentiating HGSOC versus SBOT achieved 91%-95% accuracy for 6485 imaging patches which have sufficient tumor and stroma cells (minimum of ten each) and 97% accuracy for classifying patients when aggregating the results to whole-slide image based on consensus.ConclusionsCellular features digitally extracted from pathological images can be used for cell classification and SBOT v. HGSOC differentiation. Introducing digital pathology into ovarian cancer research could be beneficial to discover potential clinical implications. A larger cohort is required to further evaluate the system.
| S-EPMC8356706 | biostudies-literature
Project description:BackgroundTo evaluate the effect of clinicopathologic factors on the prognosis and fertility outcomes of BOT patients.MethodsWe performed a retrospective analysis of BOT patients who underwent surgical procedures in West China Second University Hospital from 2008 to 2015. The DFS outcomes, potential prognostic factors and fertility outcomes were evaluated.ResultsFour hundred forty-eight patients were included; 52 recurrences were observed. Ninety-two patients undergoing FSS achieved pregnancy. No significant differences in fertility outcomes were found between the staging and unstaged surgery groups. Staging surgery was not an independent prognostic factor for DFS. Laparoscopy resulted in better prognosis than laparotomy in patients with stage I tumours and a desire for fertility preservation.ConclusionPatients with BOT fail to benefit from surgical staging. Laparoscopy is recommended for patients with stage I disease who desire to preserve fertility. Physicians should pay more attention to risk of recurrence in patients who want to preserve fertility.
| S-EPMC7433083 | biostudies-literature
Project description:ObjectiveOvarian fibromas and adenofibromas are rare ovarian tumours. They are benign tumours composed of spindle-like stromal cells (pure fibroma) or a mixture of fibroblast and epithelial components (adenofibroma). We have previously shown that 40% of benign serous ovarian tumours are likely primary fibromas due to the neoplastic alterations being restricted to the stromal compartment of these tumours. We further explore this finding by comparing benign serous tumours to pure fibromas.ResultsPerforming copy number aberration (CNA) analysis on the stromal component of 45 benign serous tumours and 8 pure fibromas, we have again shown that trisomy of chromosome 12 is the most common aberration in ovarian fibromas. CNAs were more frequent in the pure fibromas than the benign serous tumours (88% vs 33%), however pure fibromas more frequently harboured more than one CNA event compared with benign serous tumours. As these extra CNA events observed in the pure fibromas were unique to this subset our data indicates a unique tumour evolution. Gene expression analysis on the two cohorts was unable to show gene expression changes that differed based on tumour subtype. Exome analysis did not reveal any recurrently mutated genes.
| S-EPMC7376903 | biostudies-literature
Project description:The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear localization similarities between BOTs and LGSCs and not HGSCs support the hypothesis suggesting evolution of LGSCs from BOTs. We also confirm that EGFR mutations and amplifications are not molecular events in the pathogenesis of BOTs.
| S-EPMC4891141 | biostudies-literature
Project description:Objectives and goals: The causes and molecular pathology of ovarian cancer are essentially unknown. However, it is generally understood that serous ovarian borderline tumors (SBOT) and well differentiated (WD) serous ovarian carcinomas (SC) have a similar tumorigenetic pathway, distinct from moderately (MD) and poorly differentiated (PD) SC. The aim of this study was to identify mRNAs differentially expressed between MD/PD SC, SBOT and superficial scrapings from normal ovaries (SNO),and to correlate these mRNAs with clinical parameters. Results: From the global gene expression analyses, thirty mRNAs differentially expressed between MD/PD SC, SBOT and SNO were selected and validated by RT-qPCR, verifying 21 mRNAs to be significantly differentially expressed (p<0.01). Of these, 13 mRNAs were differentially expressed in MD/PD SC compared with SNO (p<0.01) and were correlated with clinical parameters. VEGFA was significantly upregulated (FC=6.1, p=6.0x10-6), and correlated with progression-free survival (p=0.037). ZNF385B was significantly downregulated (FC=-130.5, p=1.2x10-7), and correlated with overall survival (p=0.03). An increased TPX2 (p=0.03) and FOXM1 (p=0.044) expression correlated with optimal normalization of serum CA125 after treatment. Furthermore, we present a common molecular pathway for MD/PD SC, including VEGFA, FOXM1, TPX2, BIRC5 and TOP2A, all significantly upregulated and interacting with TP53. Conclusions: We have identified 21 mRNAs differentially expressed (p<0.01) between MD/PD SC, SBOT and SNO. Thirteen were differentially expressed in MD/PD SC, including VEGFA and ZNF385B, correlating with survival, and FOXM1 and TPX2, correlating with normalization of serum CA125.
2012-09-28 | GSE36668 | GEO
Project description:The aims of the present study were to find the frequency of the most common BRCA1 mutations in women with ovarian tumours identified from a population-based cancer registry and in the general population, to estimate the relative risk of ovarian tumours among the mutation carriers, and to explore the value of using CA125 as a prediagnostic test. The study was designed as a nested case-control study within a cohort mainly consisting of participants in population-based health examinations. The data files of The Cancer Registry of Norway and the Janus serum bank were linked to identify cases with ovarian cancer and borderline tumours. Hereditary BRCA1 mutations were determined using archived serum samples and capillary electrophoresis. Altogether 478 ovarian cancer patients and 190 patients with borderline tumours were identified, and 1421 and 568 matching controls were selected. Odds ratios (OR) of developing ovarian cancer and borderline tumours in the presence of BRCA1 mutations and CA125 level were derived from conditional logistic regression models. Among the 478 ovarian cancer patients, 19 BRCA1 mutations were identified (1675delA, 1135insA, 816delGT and 3347delAG), none among the patients with borderline tumours. Only two of the 1989 controls were BRCA1 mutation carriers (0.10%). The risk of ovarian cancer among the mutation carriers was strongly elevated (OR=29, 95% CI=6.6-120). CA125 was a marker for ovarian cancer, but the sensitivity was low. This study showed that BRCA1 mutation carriers have a very high risk of ovarian cancer. However, since the prevalence of BRCA1 mutations in the Norwegian population was low, the proportion of ovarian cancers due to BRCA1 mutations seemed to be low, about 4%. The sensitivity of using CA125 only as a screening test for ovarian cancer was low.
| S-EPMC2410048 | biostudies-other