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The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI ≥ 50% (risk ratio [RR] = 4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI ≥ 50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not. [ABSTRACT FROM AUTHOR]

The expression of placental alkaline phosphatase in 116 ovarian epithelial tumours was examined in formalin-fixed tissues used for routine histopathologic examination. In the total material, 51 % of the tumours displayed positive immunoreactivity, as described by the monoclonal anti-placental alkaline phosphatase antibody C2, with similar incidence (46-67%) in the four major groups of the adenocarcinomas, i.e., serous, mucinous, endometrioid and mesonephric tumours. By use of a histochemical staining index the mucinous and mesonephric tumours demonstrated a more intense staining (2.1 and 2.6) compared to the serous and endometrioid tumours (0.9 and 1.5). The relevance of the findings is discussed in relation to the use of monoclonal antibody technologies for radioimmunolocalization and radioimmunotherapy. Copyright © 1989 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background:The peak in incidence of ovarian cancer occurs around 65 years and concurrent increasing risk by age for a number of diseases strongly influence treatment and prognosis. The aim was to explore prevalence and incidence of co-morbidity in ovarian cancer patients compared with the general population.Methods:The study population was patients with ovarian cancer in Sweden 1993-2006 (n=11 139) and five controls per case (n=55 687). Co-morbidity from 1987 to 2006 was obtained from the Swedish Patient Register. Prevalent data were analysed with logistic regression and incident data with Cox proportional hazards models.Results:Women developing ovarian cancer did not have higher overall morbidity than other women earlier than 3 months preceding cancer diagnosis. However, at time of diagnosis 11 of 13 prevalent diagnosis groups were more common among ovarian cancer patients compared with controls. The incidence of many common diagnoses was increased several years following the ovarian cancer and the most common diagnoses during the follow-up period were thromboembolism, haematologic and gastrointestinal complications.Conclusion:Women developing ovarian cancer do not have higher overall morbidity the years preceding cancer diagnosis. The incidence of many common diagnoses was increased several years following the ovarian cancer. It is crucial to consider time between co-morbidity and cancer diagnosis to understand and interpret associations. [ABSTRACT FROM AUTHOR]

Objective: This study compared the effectiveness, safety, and tolerability of dose-dense paclitaxel and carboplatin plus bevacizumab (ddTC+Bev) with ddTC for advanced ovarian cancer. Methods: We retrospectively analyzed the clinical records of 134 patients who received ddTC+Bev or ddTC as first-line chemotherapy for stage III-IV ovarian cancer. Progressionfree survival as primary endpoint of this study was compared using the log-rank test. Cox proportional hazards model and propensity score matching (PSM) were used to analyze prognostic factors, and the frequency of adverse events was examined using the χ2 test. Results: We categorized 134 patients in the ddTC+Bev (n=57) and ddTC (n=77) groups who started treatment at four related institutions from November 2013 to December 2017. No patients used poly (ADP-ribose) polymerase inhibitors as the first line maintenance therapy. The progression-free survival (PFS) of the ddTC+Bev group had a significantly better prognosis than that of the ddTC group (hazard ratio [HR]=0.50; 95% confidence interval [CI]=0.32-0.79; p<0.003). Multivariate analysis showed that ddTC+Bev regimen was a prognostic factor. However, intergroup comparison using PSM revealed that the PFS of the ddTC+Bev group had a nonsignificantly better prognosis than that of the ddTC group (HR=0.70; 95% CI=0.41-1.20; p=0.189). Few adverse events above G3 were noted for ddTC+Bev, which were sufficiently tolerable. Conclusion: This study could not demonstrate that adding Bev to ddTC improves prognosis. Further studies with more cases are warranted. [ABSTRACT FROM AUTHOR]

The immunohistochemically detectable expression of CA-125 and CEA in ovarian tumor tissue from 187 patients was related to corresponding preoperative serum levels. A strong positive association between tissue expression and the serum level of both the CA-125 and CEA antigens was found in cases of invasive epithelial ovarian carcinoma. However, this relationship was absent for CA-125 in borderline cases and patients with benign ovarian tumors, although the antigen frequently was detectable in them. The presence of ascites could be verified in 3 of 10 cases with benign CA-125 negative tumors, but elevated CA-125 levels in serum. ‘False negative’ CA-125 levels were found in 6 borderline and 7 true invasive carcinoma cases despite positive tissue staining. Eight of those patients had limited stage I disease. The data suggests that although the tissue expression of the CA-125 and CEA antigens in invasive ovarian carcinoma has an important influence in the corresponding serum level, compartment barriers and low cell turnover in benign, and to a lesser extent borderline, cases result in low serum levels. In addition, other factors influence serum levels of CA-125, such as secondary peritoneal response with or without ascites, which may cause ‘falsely elevated’ CA-125 results in benign disease. [ABSTRACT FROM AUTHOR]

In a prospective study the immunohistochemically detectable tissue expression of the antigens CA-125 and CEA in 112 epithelial ovarian carcinomas and 23 borderline tumors was related to histologic features of the tumor and to patient survival. The CA-125 antigen was expressed mainly in non-mucinous tumors, with no evident association between histologic grade and immunoreactivity. CEA was expressed in mucinous tumors regardless of tumor grade. Flow cytometric DNA analysis was performed on fresh frozen tissue in a subgroup of 60 cases. There was no association between DNA ploidy or S-phase fraction and the CA-125 or CEA antigen expression. Tumor stage, size of residual tumor masses after surgery and DNA ploidy had independent associations with patient survival in multivariate log-rank analysis of prognostic factors. However, there was no association between the CA-125 or CEA antigen expression and patient survival. Thus, in ovarian carcinoma the expression of the CA-125 and CEA antigens seems to be independent of the inherent malignant potential of the tumor epithelium, while DNA analysis provides valuable prognostic information. [ABSTRACT FROM AUTHOR]

Background: Non-endometrioid endometrial carcinomas (NEEC) are characterized by their rarity and adverse prognoses. This study evaluates the outcomes of open versus minimally invasive surgery (MIS) in NEEC patients stratified by prognostic risks according to the 2020 ESGO-ESTRO-ESP risk classification guidelines. Methods: A retrospective analysis was performed on 99 NEEC patients who underwent initial surgery at Fujian University Cancer Hospital. Patients were categorized into two groups: those undergoing MIS and those undergoing open surgery. We compared disease-free survival (DFS) and overall survival (OS) between these groups. Cox regression analysis was employed to identify risk factors for DFS, which were further validated via bootstrap statistical methods. Results: The study included 31 patients in the MIS group and 68 in the open surgery group. The demographics and clinical characteristics such as age, body mass index, comorbidities, histological subtypes, and FIGO stage were similar between groups (P > 0.05). The MIS group experienced ten recurrences (1 vaginal, 2 lymph nodes, 7 distant metastases), whereas the open surgery group had seven recurrences (1 vaginal, 3 lymph nodes, 1 pelvis, 2 distant metastases), yielding recurrence rates of 10.3% versus 25.6% (P = 0.007). Besides lymphovascular space invasion (LVSI), surgical approach was also identified as an independent prognostic factor for DFS in high-risk patients (P = 0.037, 95% CI: 1.062–7.409). The constructed nomogram demonstrated a robust predictive capability with an area under the curve (AUC) of 0.767. Survival analysis for high- and intermediate-risk patients showed no significant differences in OS between the two groups (Phigh risk = 0.275; Pintermediate−risk = 0.201). However, high-risk patients in the MIS group exhibited significantly worse DFS (P = 0.001). Conclusion: This investigation is the inaugural study to assess the impact of surgical approaches on NEEC patients within the framework of the latest ESGO-ESTRO-ESP risk classifications. Although MIS may offer clinical advantages, it should be approached with caution in high-risk NEEC patients due to associated poorer DFS outcomes. [ABSTRACT FROM AUTHOR]

Background: Isolated mediastinal metastases from ovarian carcinoma are considered exceptional. Since such metastases are considered advanced stage disease, systemic therapy is the indicated therapeutic approach; however, some articles report that surgical excision is also feasible. Methods: We reviewed the English-language literature to detect cases of isolated mediastinal ovarian cancer metastases and present the management applied as well as their outcomes. Results: From 1998 to 2022, 15 such cases have been reported, with 4 of those cases being primary ovarian cancer presentation and 11 being ovarian cancer recurrence. The histology of the tumor was serious in all of the cases. Regarding the management of cancer, various methods were applied. In total, 11 of the patients underwent a surgical resection of the mediastinal metastasis, 2 received systemic therapy, 1 received a combination of palliative chemotherapy and radiation and the last patient was treated with laser debulking and radiotherapy. The mean reported follow-up was 11 months. Conclusions: Solitary mediastinal metastasis from ovarian cancer is very rare; physicians should pay close attention when routinely evaluating thoracic scans from patients with ovarian malignancy as well as individualizing the management in such patients, since surgical resection can also be performed. However, definitive conclusions cannot be drawn from the small number of case reports available. [ABSTRACT FROM AUTHOR]

Background: CA-125 testing is a recommended first line investigation for women presenting with possible symptoms of ovarian cancer in English primary care, to help determine whether further investigation for ovarian cancer is needed. It is currently not known how well the CA-125 test performs in ovarian cancer detection for patients from different ethnic groups. Methods: A retrospective cohort study utilising English primary care data linked to the national cancer registry was undertaken. Women aged ≥ 40 years with a CA-125 test between 2010 and 2017 were included. Logistic regression predicted one-year ovarian cancer incidence by ethnicity, adjusting for age, deprivation status, and comorbidity score. The estimated incidence of ovarian cancer by CA-125 level was modelled for each ethnic group using restricted cubic splines. Results: The diagnostic performance of CA-125 differed for women from different ethnicities. In an unadjusted analysis, predicted CA-125 levels for Asian and Black women were higher than White women at corresponding probabilities of ovarian cancer. The higher PPVs for White women compared to Asian or Black women were eliminated by inclusion of covariates. Conclusion: The introduction of ethnicity-specific thresholds may increase the specificity and PPVs of CA-125 in ovarian cancer detection at the expense of sensitivity, particularly for Asian and Black women. As such, we cannot recommend the use of ethnicity-specific thresholds for CA-125. [ABSTRACT FROM AUTHOR]

Objective: In 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study. Methods: This retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People's Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model. Results: 702 EEC patients with stage I and grade 1–2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028). Conclusions: LVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature. Methods: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies. Results: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4-120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens. Conclusion: This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management. [ABSTRACT FROM AUTHOR]

Simple Summary: Low-grade serous ovarian cancer is a rare type of ovarian cancer that usually has an indolent growth and affects younger women. It has markers that suggest it might respond to hormone therapy, but unfortunately, this treatment does not work well for many patients because the cancer becomes resistant to it. We do not fully understand why this happens. In breast cancer, similar resistance mechanisms are studied, so we are exploring if we can apply what we learn there to improve treatment for this type of ovarian cancer. This review looks at why hormone therapy might stop working in ovarian cancer and explores new ways to make it more effective. The goal is to find better treatment options for patients with advanced low-grade serous ovarian cancer, who currently do not have many choices for treatment. Low-grade serous ovarian cancer (LGSOC) is a rare ovarian malignancy primarily affecting younger women and is characterized by an indolent growth pattern. It exhibits indolent growth and high estrogen/progesterone receptor expression, suggesting potential responsiveness to endocrine therapy. However, treatment efficacy remains limited due to the development of endocrine resistance. The mechanisms of resistance, whether primary or acquired, are still largely unknown and present a significant hurdle in achieving favorable treatment outcomes with endocrine therapy in these patients. In estrogen receptor-positive breast cancer, mechanisms of endocrine resistance have been largely explored and novel treatment strategies to overcome resistance have emerged. Considering the shared estrogen receptor positivity in LGSOC and breast cancer, we wanted to explore whether there are any parallel mechanisms of resistance and whether we can extend endocrine breast cancer treatments to LGSOC. This review aims to highlight the underlying molecular mechanisms possibly driving endocrine resistance in ovarian cancer, while also exploring the available therapeutic opportunities to overcome this resistance. By unraveling the potential pathways involved and examining emerging strategies, this review explores valuable insights for advancing treatment options and improving patient outcomes in LGSOC, which has limited therapeutic options available. [ABSTRACT FROM AUTHOR]

Simple Summary: For a couple of decades, the morbidity rates for endometrial cancer (EC) have been on a constant rise. Surgery is the cornerstone in the management of this disease and may be performed for curative, staging, or palliative purposes. The type of hysterectomy, the role and extent of lymphadenectomy, the procedure of the sentinel lymph node mapping, and cytoreductive surgery in advanced or recurrent EC are discussed in detail. Most recently, the introduction of the molecular classification has changed the scene in EC treatment, and its impact on choosing the surgical strategy is outlined. This narrative review focuses on the intricacies of surgical management of EC and aims at summarizing the available literature on the subject providing an up-to-date clinical guide. Endometrial cancer (EC) poses a significant health issue among women, and its incidence has been rising for a couple of decades. Surgery remains its principal treatment method and may have a curative, staging, or palliative aim. The type and extent of surgery depends on many factors, and the risks and benefits should be carefully weighed. While simple hysterectomy might be sufficient in early stage EC, modified-radical hysterectomy is sometimes indicated. In advanced disease, the evidence suggests that, similarly to ovarian cancer, optimal cytoreduction improves survival rate. The role of lymphadenectomy in EC patients has long been a controversial issue. The rationale for systematic lymphadenectomy and the procedure of the sentinel lymph node biopsy are thoroughly discussed. Finally, the impact of the molecular classification and new International Federation of Gynecology and Obstetrics (FIGO) staging system on EC treatment is outlined. Due to the increasing knowledge on the pathology and molecular features of EC, as well as the new advances in the adjuvant therapies, the surgical management of EC has become more complex. In the modern approach, it is essential to adjust the extent of the surgery to a specific patient, ensuring an optimal, made-to-measure personalized surgery. This narrative review focuses on the intricacies of surgical management of EC and aims at summarizing the available literature on the subject, providing an up-to-date clinical guide. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (EOC) is one of the most aggressive forms of gynaecological malignancies. Survival rates for women diagnosed with OC remain poor as most patients are diagnosed with advanced disease. Debulking surgery and platinum-based therapies are the current mainstay for OC treatment. However, and despite achieving initial remission, a significant portion of patients will relapse because of innate and acquired resistance, at which point the disease is considered incurable. In view of this, novel detection strategies and therapeutic approaches are needed to improve outcomes and survival of OC patients. In this review, we summarize our current knowledge of the genetic landscape and molecular pathways underpinning OC and its many subtypes. By examining therapeutic strategies explored in preclinical and clinical settings, we highlight the importance of decoding how single and convergent genetic alterations co-exist and drive OC progression and resistance to current treatments. We also propose that core signalling pathways such as the PI3K and MAPK pathways play critical roles in the origin of diverse OC subtypes and can become new targets in combination with known DNA damage repair pathways for the development of tailored and more effective anti-cancer treatments. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced cognitive impairment or "chemobrain" is a prevalent long-term complication of chemotherapy and one of the more devastating. Most of the studies performed so far to identify the cognitive dysfunctions induced by antineoplastic chemotherapies have been focused on treatment with anthracyclines, frequently administered to breast cancer patients, a population that, after treatment, shows a high possibility of long survival and, consequently, of chemobrain development. In the last few years, different possible strategies have been explored to prevent or reduce chemobrain induced by the anthracycline doxorubicin (DOX), known to promote oxidative stress and inflammation, which have been strongly implicated in the development of this brain dysfunction. Here, we have critically analyzed the results of the preclinical studies from the last few years that have evaluated the potential of phenolic compounds (PheCs), a large class of natural products able to exert powerful antioxidant and anti-inflammatory activities, in inhibiting DOX-induced chemobrain. Several PheCs belonging to different classes have been shown to be able to revert DOX-induced brain morphological damages and deficits associated with learning, memory, and exploratory behavior. We have analyzed the biological and molecular mechanisms implicated and suggested possible future perspectives in this research area. [ABSTRACT FROM AUTHOR]

Ovarian Cancer (OC) ranks as a prominent contributor to mortality among female reproductive system associated cancers, particularly the prevalent subtype epithelial Ovarian Cancer (EOC). Despite advancements in treatment modalities, the prognosis for OC patients remains grim due to limitation of current therapeutic methodology such as high cytotoxicity of chemotherapeutic agents and tumor relapse making existing chemotherapy ineffective. Recognizing the limitations of a broad-spectrum approach to treating OC, a shift toward targeted therapies aligning with unique molecular features is imperative. This shift stems from an incomplete understanding of OC's origin, distinguishing it from extensively researched malignancies such as cervical or colon cancer. At the molecular level, postsynthetic modifications--DNA, RNA, and protein--shape transcriptional, posttranscriptional, and posttranslational processes. Posttranscriptional regulatory mechanisms, including RNA modifications are termed epitranscriptomic and play critical roles in this process. For more than five decades, 100+ RNA post-synthetic modifications, notably N6-methyladenosine (m6A), most prevalent RNA modification in mammals, dynamically regulate messenger RNA (mRNA), and non-coding RNA (ncRNA) life orchestrated via writers, erasers, and readers. The disruption of m6A modifications are found in several cancers, including OC, underscores pivotal role of m6A. This review focused on m6A modifications in coding and noncoding RNAs, emphasizing their role as prognostic markers in OC and their impact on development, migration, invasion, and drug resistance. Additionally, RNA-modified regulators have been explored as potential molecular and therapeutic targets, offering an innovative approach to combatting this challenging malignancy. [ABSTRACT FROM AUTHOR]

HE4 and CA-125 are used for epithelial ovarian cancer (EOC) screening, diagnosis, and follow-up. Our objective was to study HE4 and CA-125 kinetics in patients treated for recurrent EOC. Serum samples were prospectively collected before the first chemotherapy cycle and every 3 months until disease progression. Data from 89/101 patients could be analyzed. At baseline, the median CA-125 and HE4 concentrations were 210 IU/L (7-10,310) and 184 pM (31-4,836). Among the 12 patients (13%) with normal CA-125 (<35 IU/L) concentration, eight had HE4 concentration ≥75 pM, and among the 16 patients with normal HE4 concentration (18%), 12 had increased CA-125 concentration. The median nadir concentrations were 31 IU/L (3-8,744) for CA-125 and 75 pM (20-4,836) for HE4. The median times to nadir were 14 (0-130) weeks for CA- 125 and 12 (0-52) weeks for HE4. In multivariate analysis, CA-125 and HE4 nadir concentrations (<35 IU/L, HR 0.35, 95% CI: 0.17-0.72 and<75 pM, HR 0.40, 95% CI: 0.20-0.79) and time to CA-125 and HE4 nadir (>14 weeks, HR 0.37, 95% CI: 0.20-0.70 and >12 weeks, HR 0.43, 95% CI: 0.23-0.83) were prognostic factors of progression-free survival. More investigations on HE4 kinetics could help to better monitor patients with CA-125 concentration within normal values. [ABSTRACT FROM AUTHOR]

Blood-based diagnostics for lung cancer support the diagnosis, estimation of prognosis, prediction, and monitoring of therapy response in lung cancer patients. The clinical utility of serum tumor markers has considerably increased due to developments in serum protein tumor markers analytics and clinical biomarker studies, the exploration of preanalytical and influencing conditions, the interpretation of biomarker combinations and individual biomarker kinetics, as well as the implementation of biostatistical models. In addition, circulating tumor DNA (ctDNA) and other liquid biopsy markers are playing an increasingly prominent role in the molecular tumor characterization and the monitoring of tumor evolution over time. Thus, modern lung cancer biomarkers may considerably contribute to an individualized companion diagnostics and provide a sensitive guidance for patients throughout the course of their disease. In this special edition on Tumor Markers in Lung Cancer, experts summarize recent developments in clinical laboratory diagnostics of lung cancer and give an outlook on future challenges and opportunities. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer (OC) is the most lethal gynecologic malignancy, with a relative 5-year survival rate of between 40% and 50%. We used the Cancer Registry of Baden-Württemberg to identify characteristics, treatment patterns and survival of OC patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV who were registered over a period of 8 years (2012–2019). The aim of the present analysis was to describe an unselected patient population with primary diagnoses of FIGO stage IV OC with respect to baseline patient and tumor characteristics, treatment strategies and prognosis in terms of overall survival. In this cohort of patients with FIGO stage IV OC, more than 80% of the patients received cancer-directed treatment. Age and high-grade serous histology were determinants for survival. The highest overall survival rate was observed in patients who underwent surgery followed by systemic treatment. Background: The aim of the present study was to describe an unselected population of patients with diagnosis of FIGO stage IV OC. Methods: Data from 1183 patients were available for analysis. Results: The majority of patients (962/1183, 81.3%) received cancer-directed treatment. The median follow-up time was 3.8 years, and the median overall survival duration was 1.9 years. Notably, patients >80 years had a low overall survival rate (HR of age >80 years vs. ≤50 years was 3.81, 95%-CI [2.76, 5.27], p < 0.0001). The survival rate was best in patients with HGSOC (p < 0.0001). The highest overall survival rate was observed in patients in the group with surgical intervention followed by systemic treatment, with an unadjusted HR of 0.72, 95%-CI [0.59, 0.86], p = 0.007 vs. systemic treatment only. After adjustment for age and histology, survival differences between treatment schemes were smaller (HR 0.81, 95%-CI [0.66, 1.00], p = 0.12). Conclusions: In this cohort of patients with FIGO stage IV OC, more than 80% of the patients received cancer-directed treatment. Age and high-grade serous histology were determinants for survival. The highest overall survival rate was observed in patients who underwent surgery followed by systemic treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: This review significantly contributes to the research community by providing insights into the role of serum-based biomarkers for the diagnosis of ovarian cancer. It also provides a comprehensive overview of recent advancements in immunoassay detection and employing multiplex technology and SPR biosensors to identify CA125 and HE4 biomarkers. Furthermore, it addresses the challenges associated with these diagnostic methods. This valuable information not only enhances our understanding of ovarian cancer diagnosis but also serves as a reference point for researchers and clinicians working in the field, facilitating further advancements and improvements in early detection methods. Epithelial Ovarian Cancer (EOC) is a leading cause of cancer-related deaths among women, mainly due to a lack of early detection and screening methods. Advanced immunoassay techniques, such as Luminex and proximity extension assay (PEA) technology, show promise in improving EOC detection by utilizing highly sensitive and specific multiplex panels to detect multiple combinations of biomarkers. However, these advanced immunoassay techniques have certain limitations, especially in validating the performance characteristics such as specificity, sensitivity, limit of detection (LOD), and dynamic range for each EOC biomarker within the panel. Implementing multiplexing in point-of-care (POC) biosensors can enhance EOC biomarker detection, with Surface Plasmon Resonance (SPR) being a versatile option among optical biosensors. There is no study on multiplex SPR biosensors specifically tailored for diagnosing EOC. Recent studies have shown promising results in the single detection of EOC biomarkers using SPR, with LOD for cancer antigen 125 (CA125) at 0.01 U/mL−1 and human epididymis protein 4 (HE4) at 1pM. This study proposes a potential roadmap for scientists and engineers in academia and industry to develop a cost effective yet highly efficient SPR biosensor platform for detecting EOC. [ABSTRACT FROM AUTHOR]

Simple Summary: This study compared the long-term surgical outcomes of single-port laparoscopy with other surgical methods (multi-port laparoscopy, robot-assisted laparoscopy, and laparotomy) in endometrial cancer (EC) surgical staging. After conducting propensity score matching, all surgical methods demonstrated comparable survival outcomes with respect to disease-free survival and overall survival. Consequently, single-port laparoscopy is deemed a viable option for surgical staging in EC. This single-institution, retrospective study aimed to compare the surgical outcomes of single-port, multi-port, and robot-assisted laparoscopy, as well as laparotomy, in patients with endometrial cancer who underwent surgical staging between January 2006 and December 2017. This study evaluated various parameters, including disease-free survival (DFS), overall survival (OS), recurrence rate (RR), recurrence site, and intra- and postoperative complications. Propensity score matching was performed to account for baseline characteristics, and a total of 881 patients were included in the analysis. The 3-year DFS of single-port laparoscopy was similar to that of the other groups, but laparotomy exhibited a lower 3-year DFS compared to multi-port (p = 0.001) and robot-assisted (p = 0.031) laparoscopy. Single-port laparoscopy resulted in a significantly higher 3-year OS than laparotomy (p = 0.013). After propensity score matching, the four groups demonstrated similar survival outcomes (3-year DFS: p = 0.533; 3-year OS: p = 0.328) and recurrence rates (10.3%, 12.1%, 10.3%, and 15.9% in the single-port, multi-port, and robot-assisted laparoscopy and laparotomy groups, respectively, p = 0.552). Recurrence most commonly occurred in distant organs. The single-port laparoscopy group had the longest operative time (205.1 ± 76.9 min) but the least blood loss (69.5 ± 90.8 mL) and the shortest postoperative hospital stay (5.2 ± 2.3 days). In contrast, the laparotomy group had the shortest operative time (163.4 ± 51.0 min) but the highest blood loss (368.3 ± 326.4 mL) and the longest postoperative hospital stay (10.3 ± 4.6 days). The transfusion rate was 0% in the single-port laparoscopy group and 3.7% in the laparotomy group. Notably, the laparotomy group had the highest wound complication rate (p = 0.001), whereas no wound hernias were observed in the three minimally invasive approaches. In conclusion, the survival outcomes were comparable between the methods, with the benefit of lower blood loss and shorter hospital stay observed in the single-port laparoscopy group. This study suggests that single-port laparoscopy is a feasible approach for endometrial cancer surgical staging. [ABSTRACT FROM AUTHOR]

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Background and Objective: 2D and 3D tumor features are widely used in a variety of medical image analysis tasks. However, for chemotherapy response prediction, the effectiveness between different kinds of 2D and 3D features are not comprehensively assessed, especially in ovarian-cancer-related applications. This investigation aims to accomplish such a comprehensive evaluation. Methods: For this purpose, CT images were collected retrospectively from 188 advanced-stage ovarian cancer patients. All the metastatic tumors that occurred in each patient were segmented and then processed by a set of six filters. Next, three categories of features, namely geometric, density, and texture features, were calculated from both the filtered results and the original segmented tumors, generating a total of 1403 and 1595 features for the 2D and 3D tumors, respectively. In addition to the conventional single-slice 2D and full-volume 3D tumor features, we also computed the incomplete-3D tumor features, which were achieved by sequentially adding one individual CT slice and calculating the corresponding features. Support vector machine (SVM)-based prediction models were developed and optimized for each feature set. Five-fold cross-validation was used to assess the performance of each individual model. Results: The results show that the 2D feature-based model achieved an AUC (area under the ROC curve (receiver operating characteristic)) of 0.84 ± 0.02. When adding more slices, the AUC first increased to reach the maximum and then gradually decreased to 0.86 ± 0.02. The maximum AUC was yielded when adding two adjacent slices, with a value of 0.91 ± 0.01. Conclusions: This initial result provides meaningful information for optimizing machine learning-based decision-making support tools in the future. [ABSTRACT FROM AUTHOR]

Background: Nowadays there still is no sufficient screening tool for ovarian and uterine cancer. Objective: The current study aimed to investigate whether cancer antigen 125 (CA-125), tissue polypeptide antigen (TPA) or the combination of both markers are able to act as screening tools for ovarian or uterine cancer. Methods: A total of 275 blood samples from different cohorts (ovarian cancer, uterine cancer, benign control group) were prospectively drawn and analyzed. Results: Established biomarkers TPA and CA-125 showed elevated serum concentrations in patients with malignant tumors as compared to healthy women and women with benign diseases. In ROC curve analyses, both biomarkers were well able to discriminate between malignant and healthy, benign or overall non-malignant cases in the whole sample, with AUCs of 0.842 and above. While TPA was the best diagnostic marker in patients with uterine cancer, CA 125 was the best in patients with ovarian cancer. Conclusions: TPA and CA-125 both showed promising results for the detection of gynecologic malignancies. The combination of CA-125 and TPA did not improve sensitivity in comparison to single markers. [ABSTRACT FROM AUTHOR]

The major histocompatibility complex (MHC) loci, the most polymorphic regions within the human genome, encode protein complexes responsible for antigen presentation and CD4+ and CD8+ cell activation. In prostate cancer (PCa), the second most diagnosed cancer in the male population, MHC loci undergo significant changes in their expression patterns, which affect the ability of the immune system to attack and eliminate malignant cells. The purpose of this study was to explore the genetic diversity of human leukocyte antigen (HLA)-A and HLA-B in patients with PCa and healthy controls (HCs) by performing HLA genotyping using NGS technology. The analysis highlighted statistically significant differences (p < 0.05) in the prevalence of three alleles (A*11:01, A*24:02, and B*18:01). Among the HCs analyzed, 14.89% had A*11:01, 20.21% had A*24:02, and 30.61% had B*18:01; while 5.21% of patients with PCa presented A*11:01, 9.38% presented A*24:02, 18.08% presented B*18:01. Odds ratio (OR) calculations underlined a negative association between the three alleles and the risk of PCa (OR < 1). The results presented in this study suggest a protective role of A*11:01, A*24:02, and B*18:01 in PCa. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer is often diagnosed only in advanced stages, which limits therapeutic options and prognosis. Therefore, better and easily accessible methods for the early diagnosis of ovarian cancer are needed. In particular, blood-based biomarkers seem to be promising candidates for the accurate detection of ovarian cancer. We determined the concentrations of the two proteins HMGB1 and sRAGE in the sera of 231 women with ovarian cancer, benign diseases and without known gynecologic disease. In the analyses of receiver operating characteristics, both HMGB1 and sRAGE could distinguish patients with ovarian cancer from healthy women (area under the curve (AUC) 0.77 and 0.65), benign diseases (AUC 0.72 and 0.61) or all non-malignant cases (AUC 0.74 and 0.63). Moreover, the ratio of HMGB1/sRAGE differentiated even better between malignancies and other cases (AUC 0.78, 0.74 and 0.76, respectively). In conclusion, HMGB1 and sRAGE are potential candidates for the development of assays for early diagnosis of ovarian cancer and warrant inclusion in further validation studies. Background: High mobility group box 1 (HMGB1), soluble receptor of advanced glycation end products (sRAGE) and programmed cell death markers PD-1 and PD-L1 are immunogenic serum biomarkers that may serve as novel diagnostic tools for cancer diagnosis. Methods: We investigated the four markers in sera of 231 women, among them 76 with ovarian cancer, 87 with benign diseases and 68 healthy controls, using enzyme immunoassays. Discrimination between groups was calculated using receiver operating characteristic (ROC) curves and sensitivities at fixed 90% and 95% specificities. Results: HMGB1 levels were significantly elevated and sRAGE levels were decreased in cancer patients as compared to benign and healthy controls. In consequence, the ratio of HMGB1 and sRAGE discriminated best between diagnostic groups. The areas under the curve (AUCs) of the ROC curves for differentiation of cancer vs. healthy were 0.77 for HMGB1, 0.65 for sRAGE and 0.78 for the HMGB1/sRAGE ratio, and slightly lower for the differentiation of cancer vs. benigns with 0.72 for HMGB1, 0.61 for sRAGE and 0.74 for the ratio of both. The highest sensitivities for cancer detection at 90% specificity versus benign diseases were achieved using HMGB1 with 41.3% and the HMGB1/sRAGE ratio with 39.2%, followed by sRAGE with 18.9%. PD-1 showed only minor and PD-L1 no power for discrimination between ovarian cancer and benign diseases. Conclusion: HMGB1 and sRAGE have differential diagnostic potential for ovarian cancer detection and warrant inclusion in further validation studies. [ABSTRACT FROM AUTHOR]

Introduction: A study of tumor resectability in pre-operative patients with advanced epithelial ovarian cancer is required to predict primary surgical benefits accurately. This study aims to investigate IL6, CA-125 and HE4 to predict tumor resectability in the pre-operative patients with advanced epithelial ovarian cancer. Methods: This cross-sectional study was conducted in the polyclinic, oncology and gynecology inpatient room of Dr. M. Jamil Padang Hospital from June until December 2022. Advanced epithelial ovarian cancer stage based on histology result from FIGO stages IIIB–IVA. IL6, CA-125, and HE4 were measured using ECLIA (electrochemiluminescence immunoassay). Categorical data were assessed using Chi-square and Mann-Whitney tests. Numerical variable correlations were analyzed using Pearson Correlation tests. While the correlation between numerical and nominal variables was analyzed using the Eta correlation test. A p-value of <0,05 was considered a significant correlation. The cut-off value of serum IL6, CA-125, and HE4 was determined with a ROC curve. The sensitivity and specificity of each clinical parameter were calculated. Results: There was a significant difference in IL-6 (1328 vs 752 pg/ml; p<0,001), CA-125 (1260,5 vs 819,5 U/ml; p<0,001), and HE4 levels (1320 vs 760 pmol/L; p<0,001) between patients with tumor resectability of > 1 cm (suboptimal) vs < 1 cm (optimal). There was a correlation between IL6 (r = 0,832), CA-125 (r = 0,716), and HE4 (r = 0,716) with tumor resectability. Conclusion: Measuring IL6, CA-125, and HE4 levels is useful for clinicians to predict tumor resectability in pre-operative patients with advanced epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

Recently, we have shown that HLA-A*02:01 and HLA-A*24:02 in de novo metastatic prostate cancer (MPCa) have an important role in disease progression. Since de novo MPCa represents a small group among patients diagnosed with prostate cancer (PCa), it was obvious to try to extend the validity of our results to larger cohorts of PCa patients. Herein, we analyzed patients irrespective of their disease status at diagnosis to include, besides patients with MPCa, those with localized PCa (LPCa). Our goal was to specify the prognostic value of HLA-A*02:01 and HLA-A*24:02 for overall survival (OS) prospectively and for early biochemical recurrence (BCR) and castrate resistance (CR) as additional clinical endpoints in a prospective/retrospective manner, to improve clinical decisions for patients covering all stages of PCa. On univariate analysis, HLA-A alleles were significantly associated as prognostic biomarkers with early BCR (p = 0.028; HR = 1.822), OS (p = 0.013; HR = 1.547) and showed a trend for CR (p = 0.150; HR = 1.239). On multivariate analysis, HLA-A alleles proved to be independent prognosticators for early BCR (p = 0.017; HR = 2.008), CR (p = 0.005; HR = 1.615), and OS (p = 0.002; HR = 2.063). Kaplan–Meier analyses revealed that patients belonging to the HLA-A*02:01+HLA-A*24:02− group progressed much faster to BCR and CR and had also shorter OS compared to HLA-A*24:02+ patients. Patients being HLA-A*02:01−HLA-A*24:02− exhibited varying clinical outcomes, pointing to the presence of additional HLA-A alleles with potential prognostic value. Our data underline the HLA-A alleles as valuable prognostic biomarkers for PCa that may assist with the appropriate treatment and follow-up schedule based on the risk for disease progression to avoid over-diagnosis and over-treatment. [ABSTRACT FROM AUTHOR]

Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings. [ABSTRACT FROM AUTHOR]

Introduction: Gynecological cancers account for a large number of cancer-related deaths in women. Endometrial cancer is the most prevalent, while ovarian cancer is the deadliest gynecological cancer worldwide. To overcome the clinical need for easy and rapid testing, there is a growing interest in cancer detection in non-invasive modalities. With a growing field of liquid biopsy, urine became interesting source of cancer biomarkers. Objectives: The aim of this manuscript is to provide an overview on the origin, analysis and the clinical significance of urine microRNAs in gynecological cancers, with a focus on ovarian and endometrial cancer. MicroRNAs, a class of small non-coding nucleic acids, are emerging as a non-invasive biomarkers due to the feasibility and the extreme stability in body fluids. Specific miRNA expression signatures have been previously identified in ovarian and endometrial cancer. Results: The aim of this manuscript is to provide an overview on the origin, analysis and the clinical significance of urine microRNAs in gynecological cancers, with the focus on ovarian and endometrial cancer. Conclusion: The advantages and limitations of urine microRNA utility and technologies are discussed. Previously detected microRNA from urine of the patients are summarized to evaluate their potential as non-invasive clinical biomarkers in gynecological oncology. [ABSTRACT FROM AUTHOR]

Brenner tumors of the ovary are very rare, and mostly benign. Borderline Brenner tumors are rare and malignant Brenner tumors are even much rarer with a worse prognosis. This study was carried out in the Department of Pathology, VSSIMSAR, Burla, Odisha over a period of 3 years. A histopathology study was done in all the cases, while immunostaining was done in selected cases only. A total of seven cases were studied, out of which four (57.14%) cases were diagnosed as benign Brenner tumors, two (28.57%) cases as borderline Brenner tumors, and one (14.28%) case as malignant. Histopathology study is the gold standard for diagnosis of Brenner tumor, with the aid of immunostain whenever necessary. [ABSTRACT FROM AUTHOR]

Ovarian cancer, especially high-grade serous type, is the most lethal gynecological malignancy. The lack of screening programs and the scarcity of symptomatology result in the late diagnosis in about 75% of affected women. Despite very demanding and aggressive surgical treatment, multiple-line chemotherapy regimens and both approved and clinically tested targeted therapies, the overall survival of patients is still unsatisfactory and disappointing. Research studies have recently brought some more understanding of the molecular diversity of the ovarian cancer, its unique intraperitoneal biology, the role of cancer stem cells, and the complexity of tumor microenvironment. There is a growing body of evidence that individualization of the treatment adjusted to the molecular and biochemical signature of the tumor as well as to the medical status of the patient should replace or supplement the foregoing therapy. In this review, we have proposed the principles of the novel regimen of the therapy that we called the "DEPHENCE" system, and we have extensively discussed the results of the studies focused on the ovarian cancer stem cells, other components of cancer metastatic niche, and, finally, clinical trials targeting these two environments. Through this, we have tried to present the evolving landscape of treatment options and put flesh on the experimental approach to attack the high-grade serous ovarian cancer multidirectionally, corresponding to the "DEPHENCE" system postulates. [ABSTRACT FROM AUTHOR]

E2F-associated phospho-protein (EAPP) is known to be involved in tumor progression. However, its molecular mechanisms in epithelial ovarian cancer (EOC) remain unclear. In the present study, we found that EAPP expression was significantly higher in EOC tissues than in nontumor tissues, and aberrant EAPP expression was significantly correlated with histological grade (p = 0.019), FIGO stage (p = 0.003), histological subtype (p = 0.019), lymph node metastasis (p = 0.024), distant metastasis (p = 0.007), and Ki-67 expression (p < 0.001) in EOC. Patients with high EAPP expression had a significantly lower overall survival rate than those with low EAPP expression. More importantly, univariate and multivariate analyses suggested that the EAPP expression level and distant metastasis are independent prognostic risk factors for EOC patients. Furthermore, we demonstrated that EAPP inhibition using siRNA was associated with decreased cell proliferation and reduced migratory and invasive capability of SK-OV-3 cells, a human EOC cell line. Together, our study reveals that high expression of EAPP may indicate poor prognosis and play an essential role in EOC progression. EAPP may, therefore, serve as a potential biomarker and a novel therapeutic target for EOC patients. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer has the worst outcome among gynecological malignancies; therefore, biomarkers that could contribute to the early diagnosis and/or prognosis prediction are urgently required. In the present study, we focused on the secreted protein spondin-1 (SPON1) and clarified the prognostic relevance in ovarian cancer. Methods: We developed a monoclonal antibody (mAb) that selectively recognizes SPON1. Using this specific mAb, we determined the expression of SPON1 protein in the normal ovary, serous tubal intraepithelial carcinoma (STIC), and ovarian cancer tissues, as well as in various normal adult tissues by immunohistochemistry, and verified its clinicopathological significance in ovarian cancer. Results: The normal ovarian tissue was barely positive for SPON1, and no immunoreactive signals were detected in other healthy tissues examined, which was in good agreement with data obtained from gene expression databases. By contrast, upon semi-quantification, 22 of 242 ovarian cancer cases (9.1%) exhibited high SPON1 expression, whereas 64 (26.4%), 87 (36.0%), and 69 (28.5%) cases, which were designated as SPON1-low, possessed the moderate, weak, and negative SPON1 expression, respectively. The STIC tissues also possessed SPON1-positive signals. The 5-year recurrence-free survival (RFS) rate in the SPON1-high group (13.6%) was significantly lower than that in the SPON1-low group (51.2%). In addition, high SPON1 expression was significantly associated with several clinicopathological variables. Multivariable analysis revealed that high SPON1 was an independent prognostic factor for RFS of ovarian cancer. Conclusions: SPON1 represents a prognostic biomarker for ovarian cancer, and the anti-SPON1 mAb could be valuable as an outcome predictor. [ABSTRACT FROM AUTHOR]

Background/Aim: Epithelial ovarian cancer (EOC) is usually diagnosed in advanced stages and has a high mortality rate. In this study, we used the proximity extension assay from Olink Proteomics to search for new plasma protein biomarkers to predict overall survival (OS) in patients with EOC. Materials and Methods: Peripheral blood samples were obtained preoperatively from 116 EOC patients undergoing primary debulking surgery: 28 early EOC cases (FIGO stage I-II) and 88 advanced EOC cases (FIGO stage III-IV). Proteins were measured using the Olink Oncology II and Inflammation panels. In total, 177 unique protein biomarkers were analysed. Cross-validation and LASSO regression were combined to select prediction models for OS. Results: The model including age and the three-biomarker combination of neurotrophin-3 (NT-3)+transmembrane glycoprotein NMB (GPNMB)+mesothelin (MSLN) predicted worse OS with AUC=0.79 (p=0.004). Adding cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to the model further improved performance (AUC=0.83; p=0.003). In a postoperative model including age and stage (III+IV vs. I+II), the three-biomarker panel of chemokine (C-C motif) ligand 28 (CCL28)+T-cell leukaemia/lymphoma protein 1A (TCL1A)+GPNMB improved the prediction of OS (from AUC=0.83 to AUC=0.90; p=0.05). In the postoperative model including age and dichotomized stage (III vs. I+II), the biomarkers CCL28 and GPNMB1 improved the prediction of OS (AUC=0.86; p<0.001). The combination of high levels of both CA125 and HE4 predicted worse survival (p=0.05). Conclusion: In this explorative study evaluating the performance of plasma protein biomarkers in predicting OS, we found that adding biomarkers, especially NT-3, to the panel improved the prediction of OS. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is an aggressive disease, primarily diagnosed in late stages with only 20% of patients surviving more than 5 years. Liquid biopsy markers have great potential to improve current diagnostic and prognostic methods. Here, we compared miRNAs and DNA methylation in matched plasma, whole blood and tissues as a surrogate marker for OC. We found that while both cfDNA and cf-miRNAs levels were upregulated in OC compared to patients with benign lesions or healthy controls, only cf-miRNA levels were an independent prognosticator of survival. Following on our previous work, we found members of the miR-200 family, miR-200c and miR-141 to be upregulated in both plasma and matched tissues of OC patients which correlated with adverse clinical features. We could also show that the upregulation of miR-200c and -141 correlated with promoter DNA hypomethylation in tissues, but not in plasma or matched whole blood samples. As cf-miRNAs are more easily obtained and very stable in blood, we conclude that they might serve as a more appropriate surrogate liquid biopsy marker than cfDNA for OC. [ABSTRACT FROM AUTHOR]

Simple Summary: The identification of prognostic factors is important to improve the management of patients with ovarian cancer (OC). The staging classification of OC was revised in 2014 and 2018 by the FIGO (International Federation of Gynecology and Obstetrics) Gynecological Oncology Committee and dichotomizes stages IV into stage IVA and IVB. The FIGO classification aims to establish a disease severity scale and to group patients with similar prognoses. The objective of our retrospective, multicenter study was to assess the prognostic impact of this dichotomization and of the initial metastatic localization of patients with FIGO stage IV OC. We showed that, among our 307 patients, FIGO stage IVA patients had a worse prognosis than FIGO stage IVB patients. The initial pleural effusion was a factor of poor prognosis in terms of overall survival. We suggest a modification of the current FIGO staging classification. International Federation of Gynecology and Obstetrics (FIGO) staging classification for stage IV epithelial ovarian cancer (EOC) separates stages IVA (pleural effusion) and IVB (parenchymal and/or extra-abdominal lymph node metastases). We aimed to evaluate its prognostic impact and to compare survival according to the initial metastatic location. We conducted a multicenter study between 2000 and 2020, including patients with a FIGO stage IV EOC. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and recurrence rates. We included 307 patients: 98 (32%) had FIGO stage IVA and 209 (68%) had FIGO stage IVB. The median OS and PFS of stage IVA patients were significantly lower than those of stage IVB patients (31 versus 45 months (p = 0.02) and 18 versus 25 months (p = 0.01), respectively). Recurrence rate was higher in stage IVA than IVB patients (65% versus 47% (p = 0.004)). Initial pleural involvement was a poor prognostic factor with a median OS of 35 months versus 49 months for patients without initial pleural involvement (p = 0.024). Patients with FIGO stage IVA had a worse prognosis than patients with FIGO stage IVB EOC. Pleural involvement appears to be relevant for predicting survival. We suggest a modification of the current FIGO staging classification. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To analyze the expression profile of placental type alkaline phosphatase (PLAP), cancer antigen 125 (CA125), and human epididymis protein 4 (HE4) in serous ovarian cancer and to correlate their expression with the tumor aggressiveness and progression. METHODS: Retrospective study considering a tissue microarray of 82 women affected by ovarian serous cancer. Protein expression was assessed by immunohistochemistry on ovarian serous cancer tissue samples. Immunohistochemical staining was semiquantitatively evaluated as H-score. RESULTS: Median H-score values were lower for PLAP, 1 (IQR 0-4) than CA125, 10 (IQR 6-12) or HE4, 8 (IQR 5-12). Even if PLAP was less expressed in the cells of serous ovarian cancer than CA125 or HE4 it was relatively more expressed in the fourth quartile of its H-score distribution among cases with low CA125 or HE4 expression. Furthermore, PLAP and HE4 high expression resulted to be significantly correlated with a better prognosis. CONCLUSIONS: PLAP could be an additional marker for early detection of serous ovarian carcinoma, together with the established CA125 and HE4. In addition, PLAP expression is correlated with prognosis, giving, in this way, an additional tool for improving treatment approach. [ABSTRACT FROM AUTHOR]

Simple Summary: Since the identification of a large variety of biomarkers in B cell malignancies as being driving factors for tumor progression and patient prognosis, their targeting may confer valuable options for the treatment of these diseases. Over the past 20 years, the permanent development of a multitude of inhibitors acting on survival-associated biomarkers has made it into clinical evaluation in B lymphoid tumors. Although certain drugs approved by the US Food and Drug Administration improve clinical outcome, some patients do not respond and others relapse. This review summarizes the current state-of-the-art, provides a summary of new, safer, more selective inhibitors currently under evaluation in clinical trials, and highlights the emerging positioning of metabolic drugs in tumor B cell biology as a promising strategy to be translated into clinical practice. Resistance to death is one of the hallmarks of human B cell malignancies and often contributes to the lack of a lasting response to today's commonly used treatments. Drug discovery approaches designed to activate the death machinery have generated a large number of inhibitors of anti-apoptotic proteins from the B-cell lymphoma/leukemia 2 family and the B-cell receptor (BCR) signaling pathway. Orally administered small-molecule inhibitors of Bcl-2 protein and BCR partners (e.g., Bruton's tyrosine kinase and phosphatidylinositol-3 kinase) have already been included (as monotherapies or combination therapies) in the standard of care for selected B cell malignancies. Agonistic monoclonal antibodies and their derivatives (antibody–drug conjugates, antibody–radioisotope conjugates, bispecific T cell engagers, and chimeric antigen receptor-modified T cells) targeting tumor-associated antigens (TAAs, such as CD19, CD20, CD22, and CD38) are indicated for treatment (as monotherapies or combination therapies) of patients with B cell tumors. However, given that some patients are either refractory to current therapies or relapse after treatment, novel therapeutic strategies are needed. Here, we review current strategies for managing B cell malignancies, with a focus on the ongoing clinical development of more effective, selective drugs targeting these molecules, as well as other TAAs and signaling proteins. The observed impact of metabolic reprogramming on B cell pathophysiology highlights the promise of targeting metabolic checkpoints in the treatment of these disorders. [ABSTRACT FROM AUTHOR]

Simple Summary: Preoperative tumor markers and imaging often differ in predicting whether an ovarian tumor is malignant. We evaluated the correlation between the predictive values of imaging and tumor markers for diagnosing ovarian tumors, especially when there were discrepancies between the two. We found that, to prevent misidentification, it is necessary to understand the underlying disease that can increase tumor marker levels or benign tumors, which are difficult to distinguish from malignant tumors in imaging tests and several rare histopathologies with low risk of ovarian malignancy algorithm values. The malignant prediction of tumor markers and imaging was different in many patients with ovarian tumors, and this study will help to reduce the misidentification of tumors. Preoperative tumor markers and imaging often differ in predicting whether an ovarian tumor is malignant. Therefore, we evaluated the correlation between the predictive values of imaging and tumor markers for diagnosing ovarian tumors, especially when there were discrepancies between the two. We enrolled 1047 patients with ovarian tumors. The predictive values and concordance rates between the preoperative risk of ovarian malignancy algorithm (ROMA) and imaging, including CT and MRI, were evaluated. Diagnoses of 561 CT (77.9%) and 322 MRI group (69.2%) participants were consistent with the ROMA. Among them, 96.4% of the CT (541/561) and 92.5% of the MRI (298/322) group predicted an accurate diagnosis. In contrast, 67.3% (101/150) of CT and 75.2% (100/133) of MRI cases accurately predicted the diagnosis in cases with discrepancies between ROMA and CT or MRI; a total of 32% (48/150) of the CT and 25.5% (34/133) of the MRI group showed an accurate ROMA diagnosis in cases with discrepancies between ROMA and imaging. In the event of a discrepancy between ROMA and imaging when ovarian tumor malignancy prediction, the question is which method should take precedence. This study demonstrates that MRI has the greatest diagnostic accuracy, followed by CT and ROMA. It is also important to understand underlying diseases and benign conditions and rare histopathologies of malignant tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: Standard treatment of advanced stage epithelial ovarian cancer consists of cytoreductive surgery (CRS) and chemotherapy. Prolonged progression free and overall survival is correlated with the amount of residual tumor after CRS. However, cytoreductive surgery is an extensive procedure with a considerable risk of postoperative complications. Therefore, it would be valuable to have parameters that can predict the surgical outcome. In this study, we evaluated the value of the blood tumor marker CA-125 to predict complete CRS to no residual tumor. The results of our study suggest that CA-125 levels ≤35 kU/L significantly predict the surgical outcome in patients who underwent interval cytoreductive surgery, but this parameter cannot be used as an independent predictor. This contrasts with the outcome of our systematic review with mainly retrospective data, which found CA-125 as an independent predictive variable. Background: The tumor marker 'cancer antigen 125' (CA-125) plays a role in the management of women with advanced stage ovarian cancer. This study aims to describe the predictive value of pre-treatment CA-125 level and the reduction after neoadjuvant chemotherapy (NACT) on surgical outcome. Methods: A systematic review and a prospective clinical study were performed. Multiple databases were searched from database inception to April 2022. The clinical study is part of a randomized controlled trial named "PlaComOv-study". A regression analysis was performed to demonstrate correlations between preoperative CA-125 levels, CA-125 reduction after NACT, and surgical outcome. Results: Fourteen relevant articles were analyzed of which eleven reported that lower preoperative CA-125 levels were associated with a higher probability of complete cytoreduction. In the clinical study, 326 patients with FIGO stage IIIB-IV ovarian cancer who underwent CRS were enrolled from 2018 to 2020. Patients who underwent interval CRS with preoperative CA-125 levels ≤35 kU/L had higher odds of achieving complete CRS than patients with CA-125 level >35 kU/L (85% vs. 67%, OR 2.79, 95%CI 1.44–5.41, p = 0.002). In multivariable analysis with presence of ascites and peritoneal carcinomatosis, normalized preoperative CA-125 did not appear as a significant predictor for complete CRS. Conclusions: In literature, preoperative CA-125 levels ≤35 kU/L were associated with a significant higher percentage of complete CRS in univariable analysis. According to our cohort study, preoperative CA-125 level ≤35 kU/L cannot independently predict surgical outcome either for primary or interval CRS. [ABSTRACT FROM AUTHOR]