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Primary fallopian tube carcinoma (PFTC) is seldom diagnosed preoperatively and is often mistaken for epithelial ovarian carcinoma (EOC). This report details a case of primary high-grade serous carcinoma (HGSC) of the fallopian tube, highlighting radiological and clinical indicators to aid in accurate diagnosis and avoid misdiagnosis. A 46-year-old premenopausal woman presented with symptoms and a transvaginal ultrasound (TVUS) indicating a malignant ovarian tumor. Further imaging with CT and MRI revealed a solid-cystic mass suggestive of a fallopian tube tumor rather than an ovarian origin. Oncological surgery confirmed the presence of a high-grade serous carcinoma in the fallopian tube. This case underscores the diagnostic challenges of PFTC and the superior sensitivity and specificity of MRI over CT and US in distinguishing adnexal lesions. Key MRI features such as the sausage-shaped mass and associated hematosalpinx were crucial in differentiating PFTC from EOC. The report emphasizes the importance of considering PFTC in differential diagnoses of adnexal masses to ensure accurate preoperative identification.
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Neoplasias de las Trompas Uterinas , Neoplasias Ováricas , Neoplasias Peritoneales , Humanos , Femenino , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/diagnóstico , Neoplasias Ováricas/terapia , Neoplasias Ováricas/diagnóstico , Neoplasias de las Trompas Uterinas/terapia , Neoplasias de las Trompas Uterinas/diagnóstico , Reino Unido , Sociedades MédicasRESUMEN
INTRODUCTION: Epithelial ovarian cancer (EOC) is associated with the highest gynecologic cancer mortality. The development of novel, effective combinations of targeted therapeutics remains an unmet medical need. We evaluated the preclinical activity of datopotamab deruxtecan (Dato-Dxd), a novel TROP2 targeting antibody drug conjugate (ADC) in ovarian cancer cell lines and xenografts with variable TROP2 expression. METHODS: In vitro cell viability with Dato-DXd was assessed using flow-cytometry based assays against a panel of EOC primary cell lines with variable TROP2 expression. Fluorescent anti-phospho-histone H2A.X antibody was used to detect dsDNA breaks by flow-cytometry. The in vivo antitumor activity of Dato-DXd was tested in TROP2 overexpressing xenografts. RESULTS: TROP2 overexpressing (3+) and moderate (2+) expressing EOC cell lines demonstrated higher sensitivity to Dato-DXd when compared to TROP2 negative tumors. Dato-DXd exposed TROP2+ EOC demonstrated increased dsDNA breaks and Annexin-V positivity (a marker of apoptosis) when compared to tumor cells exposed to the non-binding conjugate (p = 0.001 and p = 0.016, respectively). Dato-DXd induced significant antibody-dependent cellular cytotoxicity (ADCC) in the presence of peripheral-blood-lymphocytes. While negligible activity was detected against EOC cell lines with low TROP2 expression, Dato-DXd demonstrated significant bystander killing against tumor cells with low/negligible TROP2 when such cells were admixed with TROP2 3+ tumor cells in vitro. Dato-DXd showed tumor growth suppression against EOC cell line derived xenograft models that overexpress TROP2 at 3+ levels, prolonging survival when compared to controls, with minimal toxicity. CONCLUSION: Dato-DXd shows promising preclinical activity against TROP2 overexpressing ovarian cancers. Future clinical trials in ovarian cancer patients are warranted.
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BACKGROUND: Epithelial ovarian carcinoma (EOC) is a prevalent gynaecological malignancy. The prognosis of patients with EOC is related to acetylation modifications and immune responses in the tumour microenvironment (TME). However, the relationships between acetylation-related genes, patient prognosis, and the tumour immune microenvironment (TIME) are not yet understood. Our research aims to investigate the link between acetylation and the tumour microenvironment, with the goal of identifying new biomarkers for estimating survival of patients with EOC. METHODS: Using data downloaded from the tumour genome atlas (TCGA), genotypic tissue expression (GTEx), and gene expression master table (GEO), we comprehensively evaluated acetylation-related genes in 375 ovarian cancer specimens and identified molecular subtypes using unsupervised clustering. The prognosis, TIME, stem cell index and functional concentration analysis were compared among the three groups. A risk model based on differential expression of acetylation-related genes was established through minimum absolute contraction and selection operator (LASSO) regression analysis, and the predictive validity of this feature was validated using GEO data sets. A nomogram is used to predict a patient's likelihood of survival. In addition, different EOC risk groups were evaluated for timing, tumour immune dysfunction and exclusion (TIDE) score, stemness index, somatic mutation, and drug sensitivity. RESULTS: We used the mRNA levels of the differentially expressed genes related to acetylation to classify them into three distinct clusters. Patients with increased immune cell infiltration and lower stemness scores in cluster 2 (C2) exhibited poorer prognosis. Immunity and tumourigenesis-related pathways were highly abundant in cluster 3 (C3). We developed a prognostic model for ten differentially expressed acetylation-related genes. Kaplan-Meier analysis demonstrated significantly worse overall survival (OS) in high-risk patients. Furthermore, the TIME, tumour immune dysfunction and exclusion (TIDE) score, stemness index, tumour mutation burden (TMB), immunotherapy response, and drug sensitivity all showed significant correlations with the risk scores. CONCLUSIONS: Our study demonstrated a complex regulatory mechanism of acetylation in EOC. The assessment of acetylation patterns could provide new therapeutic strategies for EOC immunotherapy to improve the prognosis of patients.
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Carcinoma Epitelial de Ovario , Neoplasias Ováricas , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Femenino , Carcinoma Epitelial de Ovario/inmunología , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/mortalidad , Carcinoma Epitelial de Ovario/patología , Carcinoma Epitelial de Ovario/metabolismo , Acetilación , Pronóstico , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Persona de Mediana EdadRESUMEN
BACKGROUND: Homologous recombination deficiency (HRD) has evolved into a major diagnostic marker in high-grade ovarian cancer (HGOC), predicting the response to poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences the treatment response and patient survival; miliary type tumor spread has a poorer predicted outcome than non-miliary type tumor spread. METHODS: Known methods for HRD assessment were adapted for our technical requirements and the predictive-value integrated genomic instability score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. RESULTS: We demonstrated that PIGIS can discriminate HRD-positive from HRD-negative samples. Tumors with a miliary tumor spread are HRD-negative and have a very bad prognosis with a progression-free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD-negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years); similar to HRD-positive tumors (PFS 34.7 months, OS 8.9 years). CONCLUSIONS: Our results indicate that in a predominantly PARPi naïve cohort, the type of tumor spread and concomitant cytoreduction efficiency is a better predictor of survival than HRD and that HRD may be an accidental surrogate marker for tumor spread and concomitant cytoreduction efficiency. It remains to be determined whether this also applies for sensitivity to PARPi.
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High-grade serous ovarian carcinoma (HGSOC) can be categorized into four gene expression-based subtypes, with supposedly distinct prognoses and treatment responses. Murakami et al. translated these gene expression-based subtypes into the histopathological mesenchymal, immunoreactive, solid and proliferative, and papilloglandular subtypes, showing differences in survival outcomes. Miyagawa et al. refined these criteria to improve the interobserver concordance. The current retrospective study evaluated the interobserver variability and the prognostic differences between the histopathologic subtypes using the criteria of both Murakami et al. and Miyagawa et al. in 208 HGSOC cases. The mesenchymal subtype was considered first, followed by the immunoreactive subtype. Non-conforming cases were categorized as solid and proliferative or papilloglandular. The mesenchymal subtype was identified in 122 patients (58.7%) for both criteria. Using the criteria of Murakami et al., 10 cases (4.8%) were immunoreactive, 26 (12.5%) solid and proliferative, and 50 (24%) papilloglandular, with a concordance rate of 62.5% (κ = 0.34, p < .001). Using the Miyagawa et al. criteria, 23 cases (11%) were immunoreactive, 20 (9.6%) solid and proliferative, and 43 (20.7%) papilloglandular. No survival differences were observed between the subtypes. The fair reproducibility of the histopathological subtype classification of HGSOC and the lack of survival differences among these subtypes indicate the need for further refinement of the criteria and exploration of their correlation with overall survival outcomes before clinical application.
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Background: INPP4B is a tyrosine-specific phosphatase in the human body, which plays an important role in the developing process of carcinogenesis. However, The correlation between INPP4B and epithelial ovarian cancer is rarely explored. In this study, the expression of INPP4B in human epithelial ovarian carcinoma and normal ovaries was detected, to explore the correlation between INPP4B expression and clinicopathological risk factors of epithelial ovarian carcinoma and to clarify its significance in the developing process of and prognosis of epithelial ovarian carcinoma. Methods: The expression of INPP4B in various tumors was detected by bioinformatics method, and the expression in epithelial ovarian cancer and normal control group was detected by Elisa. The immunohistochemical method was used in this experiment to analyze the expression of INPP4B in specimens of 100 cases of epithelial ovarian carcinoma and 20 cases of normal ovaries. Analysis of clinicopathological risk factors and related survival analysis was carried out on the expression of INPP4B in 100 cases of epithelial ovarian carcinoma. Results: The results showed that the positive expressed INPP4B protein in epithelial ovarian carcinoma was significantly less, compared with that in normal ovaries (P < 0.05). The expression of INPP4B was significantly associated with many clinicopathologic factors, such as tumor differentiation (P < 0.001), FIGO stage (P < 0.001), lymph node metastasis (P < 0.001) and distant metastasis at recurrence (P=0. 009), but not with age, pathologic type of tumor, serum CA125 at recurrence and chemotherapy sensitivity. Conclusion: In epithelial ovarian carcinoma, there is a downregulation of INPP4B expression, which may be related to poor tumor differentiation, late FIGO stage, lymph node metastasis, distant metastasis at recurrence and insensitivity to chemotherapy. Under-expression of INPP4B, lymph node metastasis, FIGO stage, and distant metastasis at recurrence are factors of poor prognostic. The under-expression level of INPP4B may be involved in the progression of epithelial ovarian carcinoma.
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OBJECTIVES: To evaluate the effect of histological subtype on oncological outcome and adjuvant platinum-based chemotherapy response in patients with epithelial ovarian cancer (EOC). MATERIAL AND METHODS: The study group was created with stage II-IV EOC patients. Progression-free survival (PFS) and disease-specific survival (DSS) estimates were determined by using the Kaplan-Meier method. The log-rank test and cox proportional hazards model were performed. RESULTS: A total 396 patients were included the study. Tumor type was serous in 332 (83.8%). Two hundred and thirty-one patients (58.3%) had maximal cytoreduction. Three hundred and twenty-seven (82.6%) patients received complete clinical response. Refractory disease was present in 69 (17.4%) patients. In patients with complete clinical response, 183 (56%) patients recurred. Five-year PFS was 32% in serous group and 31% in non-serous group (p = 0.755). Five-year DSS was 78% in serous group and 87% in non-serous group (p = 0.084). On multivariate analysis, recurrence rates 1.959 times (95% CI: 1.224-3.085; p = 0.004), death rates 2.624 times (95% CI: 1.328-5.185; p = 0.005) higher in patients with optimal cytoreduction than patients with maximal cytoreduction, respectively. CONCLUSIONS: Although the rate of maximal cytoreduction was higher in patients with non-serous tumor type, the rate of refractory disease was higher after adjuvant chemotherapy. However, the recurrence rate was higher in serous tumor type. Survival rates were similar in serous and non-serous tumor types. Maximal cytoreduction was an independent predictor factor for survival. Maximal cytoreduction should be the main target in EOC.
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Neoplasias Ováricas , Femenino , Humanos , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Platino (Metal)/uso terapéutico , Estadificación de Neoplasias , Pronóstico , Quimioterapia Adyuvante , Estudios RetrospectivosRESUMEN
PURPOSE: We aimed to differentiate serous borderline ovarian tumors (SBOT) from serous epithelial ovarian carcinomas (SEOC) using morphological and functional MRI findings, to improve the patient management. METHOD: We retrospectively investigated 24 ovarian lesions diagnosed with SBOT and 64 ovarian lesions diagnosed with SEOC. Additional to the demographic and morphological findings T2W signal intensity ratio, mean apparent diffusion coefficient (ADCmean) and total apparent diffusion coefficient (ADCtotal) values were analyzed and compared between two groups. RESULTS: Bilaterality, pelvic free fluid presence, serum CA-125 level (U/mL), presence of pelvic peritoneal implant were in favor of SEOC. Lower maximum size of solid component and solid size to maximum size ratio, dominantly cystic and solid-cystic appearance, exophytic growth pattern, presence of papiller projection and papillary architecture and internal branching pattern, higher T2W signal intensity ratio, ADCmean and ADCtotal values were in favor of SBOT. CONCLUSION: Our study revealed that morphological and functional imaging findings were valuable in differentiating BSOT from SEOC.
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Cistadenocarcinoma Seroso , Quistes Ováricos , Neoplasias Ováricas , Femenino , Humanos , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/patología , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Carcinoma Epitelial de Ovario/diagnóstico por imagen , Cistadenocarcinoma Seroso/patologíaRESUMEN
The identification of causal BRCA1/2 pathogenic variants (PVs) in epithelial ovarian carcinoma (EOC) aids the selection of patients for genetic counselling and treatment decision-making. Current recommendations therefore stress sequencing of all EOCs, regardless of histotype. Although it is recognised that BRCA1/2 PVs cluster in high-grade serous ovarian carcinomas (HGSOC), this view is largely unsubstantiated by detailed analysis. Here, we aimed to analyse the results of BRCA1/2 tumour sequencing in a centrally revised, consecutive, prospective series including all EOC histotypes. Sequencing of n = 946 EOCs revealed BRCA1/2 PVs in 125 samples (13%), only eight of which were found in non-HGSOC histotypes. Specifically, BRCA1/2 PVs were identified in high-grade endometrioid (3/20; 15%), low-grade endometrioid (1/40; 2.5%), low-grade serous (3/67; 4.5%), and clear cell (1/64; 1.6%) EOCs. No PVs were identified in any mucinous ovarian carcinomas tested. By re-evaluation and using loss of heterozygosity and homologous recombination deficiency analyses, we then assessed: (1) whether the eight 'anomalous' cases were potentially histologically misclassified and (2) whether the identified variants were likely causal in carcinogenesis. The first 'anomalous' non-HGSOC with a BRCA1/2 PV proved to be a misdiagnosed HGSOC. Next, germline BRCA2 variants, found in two p53-abnormal high-grade endometrioid tumours, showed substantial evidence supporting causality. One additional, likely causal variant, found in a p53-wildtype low-grade serous ovarian carcinoma, was of somatic origin. The remaining cases showed retention of the BRCA1/2 wildtype allele, suggestive of non-causal secondary passenger variants. We conclude that likely causal BRCA1/2 variants are present in high-grade endometrioid tumours but are absent from the other EOC histotypes tested. Although the findings require validation, these results seem to justify a transition from universal to histotype-directed sequencing. Furthermore, in-depth functional analysis of tumours harbouring BRCA1/2 variants combined with detailed revision of cancer histotypes can serve as a model in other BRCA1/2-related cancers. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Proteína BRCA1 , Neoplasias Ováricas , Femenino , Humanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Proteína p53 Supresora de Tumor , Carcinoma Epitelial de Ovario/genéticaRESUMEN
BACKGROUND: Patients with epithelial ovarian carcinoma (EOC) are usually diagnosed at an advanced stage with tumour cell invasion. However, identifying the underlying molecular mechanisms and biomarkers of EOC proliferation and invasion remains challenging. RESULTS: Herein, we explored the relationship between tumour microenvironment (TME) reprogramming and tissue invasion based on single-cell RNA sequencing (scRNA-seq) datasets. Interestingly, hypoxia, oxidative phosphorylation (OXPHOS) and glycolysis, which have biologically active trajectories during epithelial mesenchymal transition (EMT), were positively correlated. Moreover, energy metabolism and anti-apoptotic activity were found to be critical contributors to intratumor heterogeneity. In addition, HMGA1, EGR1 and RUNX1 were found to be critical drivers of the EMT process in EOC. Experimental validation revealed that suppressing EGR1 expression inhibited tumour cell invasion, significantly upregulated the expression of E-cadherin and decreased the expression of N-cadherin. In cell components analysis, cancer-associated fibroblasts (CAFs) were found to significantly contribute to immune infiltration and tumour invasion, and the accumulation of CAFs was associated with poorer patient survival. CONCLUSION: We revealed the molecular mechanism and biomarkers of tumour invasion and TME reprogramming in EOC, which provides effective targets for the suppression of tumour invasion.
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Neoplasias Ováricas , Femenino , Humanos , Carcinoma Epitelial de Ovario/genética , Neoplasias Ováricas/patología , Microambiente Tumoral/genética , Transición Epitelial-Mesenquimal/genética , Biomarcadores , Línea Celular TumoralRESUMEN
BACKGROUND: To evaluate the prognostic value of chemotherapy-induced neutropenia (CIN) in epithelial ovarian carcinoma (EOC) treated with primary surgery followed by platinum-based chemotherapy. METHODS: The records of primary EOC treated between Jan 1st 2002 and Dec 31st 2016 were reviewed according to the including and excluding criteria. CIN was defined as absolute neutrophil count (ANC) after chemotherapy <2.0 × 109/L. Patients with CIN were further divided into mild and severe CIN (ANC <1.0 × 109/L), early-onset and late-onset (>3 cycles) CIN. Clinical characteristic was compared by chi-square test. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan-Meier analysis, univariate and multivariate Cox regression models. RESULTS: Among 735 EOC patients enrolled, no significant differences of the prognosis were found between patients with and without CIN, early and late CIN, mild and severe CIN. However, Kaplan-Meier curve (65 vs 42 months for CIN vs non-CIN, P = .007) and Cox regression analysis (HR 1.499, 95% CI 1.142-1.966; P = .004) both revealed that CIN was significantly related with better OS in advanced EOC patients, but not for PFS. So, subgroup analysis was further conducted and date suggested that CIN was an independent predictor of better survival in advanced EOC with suboptimal surgery (PFS: 18 vs 14 months, P = .013, HR 1.526, 95% CI 1.072-2.171, P = .019; OS: 37 vs 27 months, P = .013, HR 1.455, 95% CI 1.004-2.108; P = .048). CONCLUSIONS: CIN might be used as an independent prognostic indicator of advanced EOC, especially for those patients with suboptimal surgery.
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Antineoplásicos , Neutropenia , Neoplasias Ováricas , Femenino , Humanos , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/cirugía , Pronóstico , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Antineoplásicos/uso terapéutico , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: MicroRNAs are a group of small non-coding RNAs that are involved in development and diseases such as cancer. Previously, we demonstrated that miR-335 is crucial for preventing collagen type XI alpha 1 (COL11A1)-mediated epithelial ovarian cancer (EOC) progression and chemoresistance. Here, we examined the role of miR-509-3p in EOC. METHODS: The patients with EOC who underwent primary cytoreductive surgery and postoperative platinum-based chemotherapy were recruited. Their clinic-pathologic characteristics were collected, and disease-related survivals were determined. The COL11A1 and miR-509-3p mRNA expression levels of 161 ovarian tumors were determined by real-time reverse transcription-polymerase chain reaction. Additionally, miR-509-3p hypermethylation was evaluated by sequencing in these tumors. The A2780CP70 and OVCAR-8 cells transfected with miR-509-3p mimic, while the A2780 and OVCAR-3 cells transfected with miR-509-3p inhibitor. The A2780CP70 cells transfected with a small interference RNA of COL11A1, and the A2780 cells transfected with a COL11A1 expression plasmid. Site-directed mutagenesis, luciferase, and chromatin immunoprecipitation assays were performed in this study. RESULTS: Low miR-509-3p levels were correlated with disease progression, a poor survival, and high COL11A1 expression levels. In vivo studies reinforced these findings and indicated that the occurrence of invasive EOC cell phenotypes and resistance to cisplatin are decreased by miR-509-3p. The miR-509-3p promoter region (p278) is important for miR-509-3p transcription regulation via methylation. The miR-509-3p hypermethylation frequency was significantly higher in EOC tumors with a low miR-509-3p expression than in those with a high miR-509-3p expression. The patients with miR-509-3p hypermethylation had a significantly shorter overall survival (OS) than those without miR-509-3p hypermethylation. Mechanistic studies further indicated that miR-509-3p transcription was downregulated by COL11A1 through a DNA methyltransferase 1 (DNMT1) stability increase. Moreover, miR-509-3p targets small ubiquitin-like modifier (SUMO)-3 to regulate EOC cell growth, invasiveness, and chemosensitivity. CONCLUSION: The miR-509-3p/DNMT1/SUMO-3 axis may be an ovarian cancer treatment target.
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MicroARNs , Neoplasias Ováricas , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Colágeno Tipo XI , Regulación hacia Abajo , Apoptosis , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/genética , Metiltransferasas , Ubiquitinas , ADN , MicroARNs/genéticaRESUMEN
INTRODUCTION: The purpose of our study was to evaluate outcome data after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis originating from advanced epithelial ovarian carcinoma (PMOC). PATIENTS AND METHODS: A retrospective international multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group. RESULTS: One thousand four hundred and ninety-one patients from 11 specialized units underwent CRS and HIPEC that of those 326 (21.9%) upfront surgeries, 504 (33.8%) interval surgery, and 661(44.3%) recurrent cases. Complete Cytoreduction(CC0/1) was achieved in 1213 patients (81.3%). Treatment -related mortality was 0.8%, major operative complications (Grades 3-5) was 25.1%. Factors associated with major operative complications include prior surgical score (PSS for recurrent cases; RC) PSS>2,p = 0.000), PCI(≤15, >15 cut-off level; p ≤ 0.000), completeness of cytoreduction (CC, p=0.000), high CA125 levels (>25 mg/dl), presence of ascites, high CRP (>5 mg/dl) levels and low albumin levels (below to 2.5 mg/dl) (p ≤ 0.05). The median survival was 58 months in upfront surgery(UFS), 60 months in interval surgery(IS), and 42 months in RC. The overall survival for five years was 45% for UFS, 37% for IS, 28% for RC cases. CCscore (p = 0.000), CA125, CRP and albumin levels (p ≤ 0.05) were predictors for progression free survival. PCI(p ≤ 0.000), major postoperative complications (p = 0.004), incomplete CRS(CC2/3)(p < 0.001), prior chemotherapy (hazard ratio [HR], 3-8; p < 0.001) and PSS>2 for RC were independent predictors of poor overall survival. CONCLUSION: The combined treatment strategy for PMOC may be performed safely with acceptable morbidity and mortality in the specialized units.
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Hipertermia Inducida , Neoplasias Ováricas , Intervención Coronaria Percutánea , Neoplasias Peritoneales , Femenino , Humanos , Carcinoma Epitelial de Ovario/terapia , Neoplasias Peritoneales/secundario , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Estudios Retrospectivos , Hipertermia Inducida/efectos adversos , Terapia Combinada , Neoplasias Ováricas/patología , Albúminas , Tasa de Supervivencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Background: Increasing epidemiological evidence supported that chronic inflammatory factors might be involved in the carcinogenesis and progression of various cancers. The present study tried to investigate the prognostic value of perioperative C-reactive protein (CRP) in prognosis of patients with epithelial ovarian carcinoma (EOC) from a tertiary university teaching hospital. Methods: The cutoff value of CRP was calculated according to receiver operating characteristic (ROC) curve. Variables were compared using Chi-square test. Progress-free survival (PFS) and overall survival (OS) time were assessed by Kaplan-Meier (KM) survival analysis and Log rank test based on serum CRP level. Univariate and multivariate Cox regression analyses were applied for assessing the relationship between clinicopathological parameters and survival. Results: Higher perioperative CRP levels (preoperative ≥5.15 mg/L and postoperative ≥72.45 mg/L) were significantly associated with serous tumor, high-grade, advanced stage, elevated preoperative CA125, suboptimal surgery, chemotherapy resistance, recurrence and death in EOC (P < 0.01). KM analysis suggested patients with elevated preoperative, postoperative and perioperative CRP had shorter survival (P < 0.01). Elevated perioperative CRP was an independent risk factor for PFS (HR 1.510, 95% CI 1.124-2.028; P = 0.006) and OS (HR 1.580, 95% CI 1.109-2.251; P = 0.011). Similar results were obtained for elevated preoperative CRP. Subgroup analysis further suggested that elevated perioperative CRP was also an independent risk factor for prognosis in advanced stage and serous EOC. Conclusion: Elevated perioperative CRP was an independent risk factor for poorer prognosis of EOC, particularly in advanced stage and serous patients.
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PURPOSE: This study aimed to investigate the impact of BRCA1/2 mutational status on survival outcomes in patients with platinum-sensitive relapsed (PSR) epithelial ovarian cancer (EOC). MATERIALS AND METHODS: We retrospectively identified patients who received secondary treatment for PSR EOC at our institution between January 2007 and June 2021 and who underwent BRCA1/2 gene testing by either germline or somatic methods. The association between BRCA1/2 mutational status and survival outcomes was evaluated. Both secondary cytoreductive surgery (CRS) and maintenance therapy were stratified considering real-world clinical practice. RESULTS: Of 262 patients, 91 (34.7%) and 171 (65.3%) were assigned to BRCA1/2 mutation and wild-type groups, respectively. The two groups had similar proportions of patients undergoing secondary CRS (26.4% vs. 32.7%, p=0.286) and maintenance therapy (54.9% vs. 46.2%, p=0.178). Overall, no differences in progression-free survival (PFS; median, 19.7 vs. 15.1 months, p=0.120) and overall survival (OS; p=0.400) were observed between the two groups. In multivariate analyses, BRCA1/2 mutational status was not associated with PFS (adjusted hazard ratio, 0.816; 95% confidence interval, 0.596 to 1.119; p=0.207). BRCA1/2 mutational status did not affect PFS among patients who underwent secondary CRS (n=80) and among those who did not (n=182) (p=0.074 and p=0.222, respectively). PFS did not differ in the BRCA1/2 mutational status among the patients who received bevacizumab maintenance (n=90, p=0.992). CONCLUSION: In this real-world evidence study, BRCA1/2 mutational status itself was not associated with PFS and OS in PSR EOC, which was consistent with whether secondary CRS or not and with bevacizumab maintenance.
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Neoplasias Ováricas , Humanos , Femenino , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/cirugía , Bevacizumab/uso terapéutico , Procedimientos Quirúrgicos de Citorreducción , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Proteína BRCA1/genéticaRESUMEN
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.
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Ovarian cancer (OC) and venous thromboembolism (VTE) have a close relationship, in which tumour cells surpass the haemostatic system to drive cancer progression. Long non-coding RNAs (lncRNAs) have been implicated in VTE pathogenesis, yet their roles in cancer-associated thrombosis (CAT) and their prognostic value are unexplored. Understanding how these lncRNAs influence venous thrombogenesis and ovarian tumorigenesis may lead to the identification of valuable biomarkers for VTE and OC management. Thus, this study evaluated the impact of five lncRNAs, namely MALAT1, TUG1, NEAT1, XIST and MEG8, on a cohort of 40 OC patients. Patients who developed VTE after OC diagnosis had worse overall survival compared to their counterparts (log-rank test, p = 0.028). Elevated pre-chemotherapy MEG8 levels in peripheral blood cells (PBCs) predicted VTE after OC diagnosis (Mann-Whitney U test, p = 0.037; Χ2 test, p = 0.033). In opposition, its low levels were linked to a higher risk of OC progression (adjusted hazard ratio (aHR) = 3.00; p = 0.039). Furthermore, low pre-chemotherapy NEAT1 levels in PBCs were associated with a higher risk of death (aHR = 6.25; p = 0.008). As for the remaining lncRNAs, no significant association with VTE incidence, OC progression or related mortality was observed. Future investigation with external validation in larger cohorts is needed to dissect the implications of the evaluated lncRNAs in OC patients.
Asunto(s)
Neoplasias Ováricas , ARN Largo no Codificante , Tromboembolia Venosa , Humanos , Femenino , ARN Largo no Codificante/genética , Tromboembolia Venosa/genética , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/genética , CarcinogénesisRESUMEN
BACKGROUND: How molecular profiles are associated with tumor microenvironment (TME) in high-grade serous ovarian cancer (HGSOC) is incompletely understood. Therefore, we analyzed the TME and molecular profiles of HGSOC and assessed their associations with overall survival (OS). METHODS: Patients with advanced-stage HGSOC treated in three Dutch hospitals between 2008-2015 were included. Patient data were collected from medical records. BRCA1/2 mutation, BRCA1 promotor methylation analyses, and copy number variations were used to define molecular profiles. Immune cells were assessed with immunohistochemical staining. RESULTS: 348 patients were categorized as BRCA mutation (BRCAm) (BRCAm or promotor methylation) (30%), non-BRCA mutated HRD (19%), Cyclin E1 (CCNE1)-amplification (13%), non-BRCAmut HRD and CCNE1-amplification (double classifier) (20%), and no specific molecular profile (NSMP) (18%). BRCAm showed highest immune cell densities and CCNE1-amplification lowest. BRCAm showed the most favorable OS (52.5 months), compared to non-BRCAmut HRD (41.0 months), CCNE1-amplification (28.0 months), double classifier (27.8 months), and NSMP (35.4 months). Higher immune cell densities showed a favorable OS compared to lower, also within the profiles. CD8+, CD20+, and CD103+ cells remained associated with OS in multivariable analysis. CONCLUSIONS: Molecular profiles and TME are associated with OS. TME differs per profile, with higher immune cell densities showing a favorable OS, even within the profiles. HGSOC does not reflect one entity but comprises different entities based on molecular profiles and TME.
RESUMEN
Most ovarian cancer patients experience disease recurrence and chemotherapeutic resistance, and the underlying mechanisms are unclear. Identifying relevant pathways could reveal new therapeutic targets. Here we examined expression of transmembrane protein 102 (TMEM102), a biomarker of prognosis and chemoresistance, in epithelial ovarian cancer (EOC), and assessed its role in inhibiting tumor cell apoptosis. We performed qRT-PCR to investigate the association of TMEM102 expression with clinical outcomes in 226 EOC patients. We also conducted in vitro studies to explore possible mechanisms through which TMEM102 may influence chemoresistance, including the effects of downregulating TMEM102 expression with small interfering RNA. Serous and high-grade carcinomas expressed significantly higher TMEM102 than normal ovarian tissues. TMEM102 was also overexpressed in patients with advanced-stage disease and chemoresistance. Reduction of TMEM102 expression by small interfering RNA induced ovarian cancer cell apoptosis after cytotoxic treatment. TMEM102 overexpression enhanced chemoresistance via upregulation of heat shock proteins 27, 60, and 70; and survivin, resulting in decreased cytochrome c in the mitochondria and decreased caspase 9 expression. Our results indicate that TMEM102 overexpression may promote chemoresistance via inhibition of a mitochondria-associated apoptotic pathway.