Search Results (90)

Background: Ovarian cancer remains the deadliest and leading cause of gynecological cancer-associated mortality in the US. The aim of this study was to characterize the trends in the incidence of ovarian cancer between premenopausal and postmenopausal women to inform future targeted interventions. Methods: This population-based cross-sectional study analyzed data from the US Cancer Statistics (USCS) database, which covered the whole of the US population between 2001 and 2021. Joinpoint regression was used to compute the average annual percentage change (APC) with 95% confidence interval (CI) and age-standardized incidence rates per 1,000,000 population. Results: The results showed that the IR of ovarian cancer declined between 2001 and 2021. Postmenopausal women had greater decreases in the IR of ovarian cancer compared to premenopausal women who showed a small decline. When stratified by race/ethnicity, non-Hispanic American Indian/Alaska Native women aged 20–49 years experienced an increase in the IR of ovarian cancer (APC = 2.4; 95% CI 0.9 to 4.1) compared to other racial/ethnic groups which showed a decline. Joinpoint trend analyses identified one inflection point in localized ovarian cancer incidence trends among all three age groups: an initial decline from 2001 to 2011 among women 20–49 years old and 65+ years old, and from 2001 to 2012 among women 50–64 years old, followed by an upward trend thereafter to 2021. Similarly, there was one inflection point in the IR of ovarian cancer for the clear cell and endometrioid types among women aged 20–49 years old. Conclusions: The IR of ovarian cancer in the US declined significantly among postmenopausal compared to premenopausal women, for whom the IR of ovarian cancer decreased only slightly. Although encouraging, these findings show a need for continued efforts to improve early detection and prevention strategies to mitigate the burden of this deadly disease. Full article

Background/Objectives: RNA-binding motif protein 3 (RBM3) is a cold-shock protein associated with a favorable prognosis in various malignancies. However, its role in epithelial ovarian cancer (OC) remains unclear. This study aimed to evaluate the prognostic significance of RBM3 expression in OC and its association with clinicopathological features. Methods: We retrospectively analyzed 183 cases of OC. Tissue microarrays were constructed using paired 2 mm tumor cores, and RBM3 expression was assessed by immunohistochemistry. Nuclear staining was semi-quantitatively scored based on intensity and proportion, generating a nuclear score (NS). Cases were classified as high (NS > 1) or low (NS ≤ 1) expression. Associations with clinicopathological parameters and survival outcomes were analyzed using chi-square tests, Kaplan–Meier survival curves, and Cox regression models. Results: High RBM3 expression was observed in 51.4% of cases and was significantly associated with favorable histologic subtypes (mucinous, endometrioid, clear cell), early International Federation of Gynecology and Obstetrics (FIGO) stage, and the absence of distant metastasis. Subgroup survival analyses stratified by histologic subtype revealed no significant differences in survival outcomes. RBM3 expression was correlated with prolonged disease-free and overall survival, although it did not retain significance in multivariate analysis. Conclusions: RBM3 expression is strongly associated with favorable pathological features in epithelial ovarian cancer. Although not an independent prognostic marker, RBM3 may serve as a complementary biomarker for risk stratification and prognosis in clinical practice. Full article

Background: Endometriosis is a benign gynecologic condition that has the risk of malignant transformation in approximately 0.5–1% of cases, most of which develop into endometriosis-associated ovarian cancers (EAOCs), such as clear cell and endometrioid adenocarcinomas. The current systematic review aims to condense recent information on the genetic and molecular mechanisms, clinical risk factors, and possible therapeutic targets of the malignant transformation of endometriosis. Methods: A systematic literature search of PubMed, Europe PMC, and Google Scholar was carried out according to PRISMA guidelines for articles published until December 2024. Following a screening of 44,629 titles, 43 full articles were included after meeting inclusion criteria. No case reports or reviews were included, and articles had to mention a malignant transformation of endometriosis and not just a diagnosis of cancer. The quality and risk of bias of studies were evaluated using ROBINS-I. Results: Malignant transformation of endometriosis is associated with genetic alterations, including ARID1A mutations, microsatellite instability, and abnormal PI3K/Akt and mTOR pathway activation. Increased oxidative stress, inflammation-driven mismatch repair deficiency, and epigenetic alterations like RUNX3 and RASSF2 hypermethylation are implicated in carcinogenesis. Clinical risk factors are advanced age (40–60 years), large ovarian endometriomas (>9 cm), postmenopausal status, and prolonged estrogen exposure. Imaging techniques like MR relaxometry and risk models based on machine learning are highly predictive for early detection. Conclusions: Endometriosis carcinogenesis is a multifactorial process driven by genetic changes, oxidative stress, and inflammatory mechanisms. Identification of high-risk individuals through molecular and imaging biomarkers may result in early detection and personalized therapy. Further research should aim at the development of more precise predictive models and exploration of precision medicine approaches to inhibit the emergence of EAOC. Full article

Background and Clinical Significance: This study presents a case of a 43-year-old female with a long history of infertility, treated for uterine leiomyoma and endometrial hyperplasia, over a total observation period of 42 months. Case Presentation: Levonorgestrel intrauterine device (LNG-IUD) therapy, as a first and subsequent line of treatment, was introduced. The patient also received medroxyprogesterone acetate oral treatment. Finally, she underwent surgery for an ovarian tumor that appeared to be an ovarian adenocarcinoma concurrent with endometrial cancer. After the removal of the reproductive organ, the patient was diagnosed with synchronous low-grade endometrioid adenocarcinoma in the endometrium and a concurrent grade 2 (G2) endometrioid adenocarcinoma in the left ovary. Conclusions: The prognosis and further management largely depend on whether these are two individual neoplasms or one metastatic tumor. Considering the young age of the patients, an early disease stage, a low grade of both cancers, and favorable prognosis, most synchronous endometrial and ovarian cancers are identified as two independent primary tumors. The diagnosis of a multi-focal neoplasm is important, as in patients with endometrial cancer and ovarian metastasis, the 5-year survival rate is 30–40%, whereas in the case of individual neoplasms, it is 75–80%. Full article

Background/Objectives: Survival rates for ovarian cancer remain distressingly low. Despite established prognostic factors, the need to identify modifiable parameters to influence survival outcomes is imperative. Overweight and obesity, both prevalent conditions, have been implicated in cancer development and potentially poor survival. However, conflicting data on the associations of body mass index (BMI) with progression-free survival (PFS) and overall survival (OS) in ovarian cancer patients necessitate further exploration. This study aims to investigate the prognostic role of BMI before chemotherapy in women with ovarian cancer, specifically focusing on PFS and OS. Methods: A retrospective analysis encompassed 1,136 patients diagnosed with ovarian carcinomas between 1995 and 2018. Patients were categorized based on BMI at presentation, and a comprehensive examination of clinicopathological, treatment, and survival data was conducted. Results: In the patient population, normal weight patients (BMI < 25 kg/m²) demonstrated a median PFS of 12.8 months (95% CI 11.7–13.9 months), while overweight/obese patients (BMI ≥ 25 kg/m²) exhibited a significantly longer median PFS of 14.9 months (95% CI 13.6–16.4 months, P = 0.006). No statistically significant difference was noted in median OS between the two BMI groups. Subgroup analysis for different histological subtypes revealed a statistically significant benefit for overweight and obese patients with serous and endometrioid histology (mPFS 12.9 months, 95% CI 11.7–14.0 vs. 15.6 months, 95% CI 13.9–17.3, P = 0.012 and 14.6 months 95% CI 13.7–15.5 vs. 25.6 months, 95% CI 9.5–41.7, P = 0.031, respectively). Additionally, BMI ≥ 25 kg/m² demonstrated a significant advantage in advanced-stage disease. Conclusions: The study underscores the intricate association between BMI and ovarian cancer prognosis. While a statistically significant difference in progression-free survival was noted between normal weight and overweight/obese patients, with the latter group experiencing a survival benefit, no such difference was observed in overall survival. Full article

Background: The phosphoinositide 3-kinase (PI3K) pathway is activated in multiple cancers. However, the significance of PIK3R1 encoding the PI3K regulatory subunit, an inhibitor of the PI3K catalytic subunit encoded by PIK3CA, in ovarian cancer development is largely unknown. Methods: Here, we investigated PIK3R1 genomic alterations and gene expression by direct sequencing and qPCR methods in 197 ovarian cancers. The results were correlated with clinicopathological and molecular variables and patient outcomes. Results: In addition to mutations (3.5%) and allelic losses (28.4%), we observed a very high frequency of decreased PIK3R1 mRNA levels in ovarian carcinomas (95.8%). Tumors with PIK3R1 mutations mostly represented low-stage cancers of endometrioid and clear-cell type. Tumors with PIK3R1 deletion and underexpression shared similar phenotypes of high-grade carcinomas (p = 0.003 and p = 0.025, respectively). Allelic loss was also associated with advanced stages (p = 0.003) and high-grade serous histotypes (p = 0.004). The PIK3R1 copy number correlated with mRNA levels (p = 0.009). PIK3R1 mutations coexisted with PTEN mutations (p = 0.041), whereas PIK3R1 deletion and underexpression were linked to PIK3CA amplification (p = 0.038 and p = 0.033, respectively). Low PIK3R1 expression diminished the probability of a complete response (OR 0.07, p = 0.03) in patients treated with platinum-based regimens. Conclusions: PIK3R1 alterations may contribute to the development of ovarian cancers with different malignant potential and molecular changes. The high frequency of PIK3R1 aberrations suggests their importance in PI3K pathway deregulation, and they may potentially serve as an alternative to PIK3CA markers for therapy with these pathway inhibitors. Full article

SWI/SNF (SWItch/Sucrose Non-Fermentable) is the most frequently mutated chromatin-remodelling complex in human malignancy, with over 20% of tumours having a mutation in a SWI/SNF complex member. Mutations in specific SWI/SNF complex members are characteristic of rare chemoresistant ovarian cancer histopathological subtypes. Somatic mutations in ARID1A, encoding one of the mutually exclusive DNA-binding subunits of SWI/SNF, occur in 42–67% of ovarian clear cell carcinomas (OCCC). The concomitant somatic or germline mutation and epigenetic silencing of the mutually exclusive ATPase subunits SMARCA4 and SMARCA2, respectively, occurs in Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), with SMARCA4 mutation reported in 69–100% of SCCOHT cases and SMARCA2 silencing seen 86–100% of the time. Somatic ARID1A mutations also occur in endometrioid ovarian cancer (EnOC), as well as in the chronic benign condition endometriosis, possibly as precursors to the development of the endometriosis-associated cancers OCCC and EnOC. Mutation of the ARID1A paralogue ARID1B can also occur in both OCCC and SCCOHT. Mutations in other SWI/SNF complex members, including SMARCA2, SMARCB1 and SMARCC1, occur rarely in either OCCC or SCCOHT. Abrogated SWI/SNF raises opportunities for pharmacological inhibition, including the use of DNA damage repair inhibitors, kinase and epigenetic inhibitors, as well as immune checkpoint blockade. Full article

Interleukin-10 (IL-10) has been shown to be present at high levels in the ascites of ovarian cancer (OC) patients; however, little is known about its prognostic value. We sought to correlate IL-10 levels in ascites and sera of OC patients with clinicopathologic characteristics and oncologic outcomes. IL-10 levels and clinical data from biobanked ascites and serum samples of OC patients were evaluated. Receiver operating characteristic curves were used to quantify marker performance and identify IL-10-high and IL-10-low groups. Correlations between IL-10 levels and clinicopathologic data were performed. Survival outcomes were calculated, while the factors affecting them were also investigated. A total of 106 patients had ascites samples, of which 44 serum samples were also available. Mean ascites IL-10 levels were significantly higher in patients with serous histology compared to endometrioid histology (p = 0.024). Fold-change in ascites IL-10 during treatment positively correlated with clinical response, as determined by a change in serum cancer antigen (CA)-125 levels (p = 0.0126). Median progression-free survival (PFS) and overall survival (OS) were shorter in patients with high compared with low ascites IL-10 levels (PFS: 18 versus 60 months; p = 0.007, OS: 42 versus 85 months; p = 0.029). A significant positive correlation was seen between ascites and sera IL-10 levels (p = 0.019). In multivariable analyses, a high ascites IL-10 level was associated with a significantly worse prognosis (PFS hazard ratio (HR) = 1.93; p = 0.02). Patients with high ascites levels of IL-10 have worse outcomes, which are likely reflective of the immunosuppressive effect of IL-10. This highlights its potential role as an immunomodulator in the tumor microenvironment, leading to OC immune evasion. Full article

We investigated whether developing an autoimmune disorder (AID) following a high-grade epithelial ovarian cancer diagnosis improves overall survival. This retrospective study included data from women treated for high-grade serous, endometrioid, or transitional cell ovarian, fallopian tube, or peritoneal cancer FIGO stage III or IV at a Swiss cantonal gynecological cancer center (2008–2023). We used Kaplan–Meier estimates and the Cox proportional hazards model using time-varying covariates for the survival function estimation. In all, 9 of 128 patients developed an AID following a cancer diagnosis. The median time from cancer diagnosis to AID was 2 years (IQR 2–5). These women survived for a median of 3031 days (IQR 1765–3963) versus 972 days (IQR 568–1819) for those who did not develop an AID (p = 0.001). The median overall survival of nine women with a pre-existing AID was 1093 days (IQR 716–1705), similar to those who never had an AID. The multivariate analyses showed older age (p = 0.003, HR 1.04, 95% CI 1.013–1.064) was associated with a poorer prognosis, and developing an AID after a cancer diagnosis was associated with longer survival (p = 0.033, HR 0.113, 95% CI 0.015–0.837). Clinical manifestations of autoimmune disorders following ovarian cancer diagnoses were associated with better overall survival (8 versus 2.7 years), indicating an overactive immune response may improve cancer control. Full article

Ovarian cancer is the most fatal of all the reproductive cancers within the female population, mainly due to its late diagnosis that limits surgery and medical treatment. Classically, ovarian cancer therapy has included conventional chemotherapy, and other therapeutic approaches are now being used to treat these patients, but the outcomes of the disease are still poor. Therefore, new strategies are needed to improve life expectancy and life quality of ovarian cancer patients. Considering that, we investigated the effect of the nutritional supplement Ocoxin Oral Solution (OOS) in ovarian cancer models. OOS contains several nutritional supplements, some of them with demonstrated antitumoral action. In vitro studies showed that OOS inhibited the proliferation of several ovarian cancer cell lines, especially of those representative of the endometrioid subtype, in a time- and dose-dependent manner. A fast cell death induction after OOS treatment was observed, and when the molecular mechanisms leading to this effect were investigated, an activation of the DNA damage checkpoint was detected, as shown by activation (phosphorylation) of CHK1 and CHK2 kinases that was followed by the phosphorylation of the target protein histone H2AX. When tested in animal models of ovarian cancer, OOS reduced tumor growth without any observed secondary effects. Moreover, such reduction in tumor proliferation was caused by the induction of DNA damage as corroborated by the in vivo phosphorylation of CHK2 and Histone H2AX. Finally, OOS potentiated the action of carboplatin or olaparib, the standard of care treatments used in ovarian clinics, opening the possibility of including OOS in combination with those standard of care agents in patients with ovarian cancer. Full article

Ovarian cancer is an umbrella term covering a number of distinct subtypes. Endometrioid and clear-cell ovarian carcinoma are endometriosis-associated ovarian cancers (EAOCs) frequently arising from ectopic endometrium in the ovary. The mechanistic target of rapamycin (mTOR) is a crucial regulator of cellular homeostasis and is dysregulated in both endometriosis and endometriosis-associated ovarian cancer, potentially favouring carcinogenesis across a spectrum from benign disease with cancer-like characteristics, through an atypical phase, to frank malignancy. In this review, we focus on mTOR dysregulation in endometriosis and EAOCs, investigating cancer driver gene mutations and their potential interaction with the mTOR pathway. Additionally, we explore the complex pathogenesis of transformation, considering environmental, hormonal, and epigenetic factors. We then discuss postmenopausal endometriosis pathogenesis and propensity for malignant transformation. Finally, we summarize the current advancements in mTOR-targeted therapeutics for endometriosis and EAOCs. Full article

Endometriosis is a frequent, estrogen-dependent, chronic disease, characterized by the presence of endometrial glands and stroma outside of the uterine cavity. Although it is not considered a precursor of cancer, endometriosis is associated with ovarian cancer. In this review, we summarized the evidence that clear-cell and endometrioid ovarian carcinomas (endometriosis-associated ovarian carcinoma—EAOC) may arise in endometriosis. The most frequent genomic alterations in these carcinomas are mutations in the AT-rich interaction domain containing protein 1A (ARID1A) gene, a subunit of the SWI/SNF chromatin remodeling complex, and alterations in phosphatidylinositol 3-kinase (PI3K) which frequently coexist. Recent studies have also suggested the simultaneous role of the PTEN tumor-suppressor gene in the early malignant transformation of endometriosis and the contribution of deficient MMR (mismatch repair) protein status in the pathogenesis of EAOC. In addition to activating and inactivating mutations in cancer driver genes, the complex pathogenesis of EAOC involves multiple other mechanisms such as the modulation of cancer driver genes via the transcriptional and post-translational (miRNA) modulation of cancer driver genes and the interplay with the inflammatory tissue microenvironment. This knowledge is being translated into the clinical management of endometriosis and EAOC. This includes the identification of the new biomarkers predictive of the risk of endometriosis and cancer, and it will shape the precision oncology treatment of EAOC. Full article

Endometriosis is a benign condition affecting women of reproductive age. A potential association with ovarian cancer has been documented. Atypical endometriosis (AE) is characterized by deviations from the typical microscopic appearance of endometriosis, including cytologic and architectural atypia. AE has been recognized as a potential precursor to endometriosis-associated ovarian cancers (EAOC), particularly endometrioid and clear cell subtypes. AE presents challenges in diagnosis due to its diverse clinical and pathological features, often requiring careful histological evaluation for accurate identification. Architectural AE, defined by localized proliferation of crowded glands with atypical epithelium resembling endometrial neoplasia, and cytologic AE, characterized by nuclear atypia within the epithelial lining of endometriotic cysts, are key subtypes. Immunohistochemical and molecular studies have revealed aberrant expression of markers such as Ki67, COX-2, BAF250a, p53, estrogen receptor, progesterone receptor, and IMP-3. Long-term follow-up studies suggest relatively low recurrence and malignant transformation rates among patients with AE, but uncertainties persist regarding its exact malignancy potential and optimal management strategies. Integration of artificial intelligence and shared molecular aberrations between AE and EAOC may enhance diagnostic accuracy. Continuous interdisciplinary collaboration and ongoing research efforts are crucial for a deeper understanding of the relationship between endometriosis and carcinogenesis, ultimately improving patient care and surveillance. Full article

Endometriosis is a chronic condition affecting reproductive-aged women, characterized by the growth of ectopic endometrial tissue. Despite being benign, endometriosis is associated with an increased risk of certain cancers, including endometriosis-associated ovarian cancer (EAOC). Ovarian cancer is rare, but more common in women with endometriosis, particularly endometrioid and clear-cell carcinomas. Factors such as hormonal imbalance, reproductive history, environmental exposures, and genetic predisposition contribute to the malignant transformation of endometriosis. Thus, understanding potential risk factors causing malignancy is crucial. Over the past few decades, various genetic mutations, microRNAs, as well as tumor microenvironmental factors have been identified, impacting pathways like PI3K/AKT/mTOR, DNA repair mechanisms, oxidative stress, and inflammation. Thus, this review aims to summarize molecular studies involved in EAOC pathogenesis as potential therapeutic targets. However, further research is needed to better understand the molecular and environmental factors driving EAOC development, to target the susceptibility of endometriotic lesions to malignant progression, and to identify effective therapeutic strategies. Full article

Background: Endometriosis affects more than 10% of reproductive-aged women, causing pelvic pain and infertility. Despite the benign nature of endometriosis, ovarian endometriomas carry a higher risk of developing endometrioid carcinomas (EnOCs) and clear cell ovarian carcinomas (CCCs). Atypical endometriosis, defined as cytological atypia resembling intraepithelial cancer, is considered the precursor of endometriosis-associated ovarian cancer (EAOC). This narrative review aims to provide an overview of EAOC, proposing a practical approach to clinical and therapeutic decision making. Methods: An electronic literature search was conducted from inception up to January 2023, using the MEDLINE database via PubMed to evaluate the existing literature on EAOC, including its pathogenesis, the diagnostic process, and the therapeutic possibilities, with articles not relevant to the topic or lacking scientific merit being excluded. Results: Eighty-one articles were included in the review to present the current state of the art regarding EAOC. A pragmatic clinical flowchart is proposed to guide therapeutic decisions and improve patient outcomes. Conclusions: Endometriosis patients may have an increased risk of developing EAOC (either EnOC or CCC). Despite not being fully accepted, the concept of AE may reshape the endometriosis–ovarian cancer relationship. Further research is needed to understand the unaddressed issues. Full article