Federation Of Gynecology Research Articles

Analysis of Clinicopathological and Molecular Features of Microcystic, Elongated, and Fragmented Pattern Invasion in Endometrioid Endometrial Cancer.

Background: Microcystic, elongated, and fragmented (MELF) invasion is a special invasion pattern in endometrioid endometrial cancer (EEC). This study aimed to investigate the clinical, pathological, and molecular features of the MELF pattern and its prognostic value in patients with EEC. Materials and Methods: The clinical and pathological data of 342 patients with EEC were retrospectively collected at Peking University People's Hospital from January 2019 to December 2022. Some key clinicopathological features were evaluated, including the tumor grade, Federation of Gynecology and Obstetrics (FIGO) staging, cervical stromal involvement, lymph node status, and lymphatic vascular space infiltration (LVSI). Immunohistochemical staining and molecular tests were performed, and the relevant literature was reviewed. Results: The MELF pattern was more prevalent in low-grade EEC. A significant correlation was found between the MELF pattern and advanced FIGO staging, LVSI, the depth of myometrial invasion, cervical stromal involvement, and lymph node metastasis (LNM). The incidence of mismatch-repair-deficient (MMRd) proteins was much higher in the MELF group than in the no-MELF group. Molecular testing revealed that, after copy number-low (CNL), microsatellite instability-high (MSI-H) was the second-most frequent subtype in the MELF group. The recurrence risk did not significantly differ between the MELF and no-MELF groups, but the differences among the four molecular subtypes were statistically significant. However, the MELF group experienced a shorter recurrence time. Among the four molecular subtypes, the recurrence risk was the highest in the CNH subgroup, followed by the MSI-H subgroup. Conclusions: MELF is a special invasion pattern in EEC and is associated with distinct clinicopathological and molecular characteristics, including the latest 2023 FIGO staging. Further research is warranted to explore its implications for treatment strategies and patient outcomes.

Sex cord ovarian tumours over 10 years: a retrospective analysis of clinicopathological profile and outcome.

To retrospectively describe the clinicopathological profile and treatment outcome of sex cord ovarian tumours (SCOTs), from a single institution. Patients who operated for SCOT between January 2011 and December 2020 were identified from the institution's discharge summaries. Treatment details and oncologic outcomes were analyzed using descriptive statistics, SPSS statistics version 21. Progression-free survival and overall survival were plotted using the Kaplan-Meier method. Over 10 years, 120 patients underwent surgery with 73 (61%) malignant SCOTs. Eight (6.6%) were referred with recurrence. Granulosa cell histology (61/73, 83.5%) and federation of gynaecology and obstetrics (FIGO) stage I disease (57/65, 78.62%) were predominant. Three (3/26,11.53%) had lymph node involvement. Adjuvant chemotherapy was advised in 53.4% (39/73).Over a median period of 47 months (1-130 months), eleven (15.06%) patients recurred (5-year recurrence rate: 9.58%) and 6 died (5-year survival rate: 89.04%).Among 65 patients with upfront disease, 9 (13.8%) recurred over a median period of 46 months (1-65 months) with 4 disease-related deaths. On univariate analysis, incomplete cytoreduction hazard ratios (HR 58.391, 95% CI 5.042-674.854), advanced FIGO stage (HR 15.931, 3.74-67.89) and nongranulosa histology was associated with recurrence. On multivariate analysis, advanced FIGO stage (HR 20.099, 95% CI 3.75-107.711) and non granulosa histology (HR 31.35, 95% 2.801-350.897 ) remained significant. Lymphadenectomy and adjuvant chemotherapy did not prevent recurrence.

Utility of Pipet Curet Cytology and Biopsy as a Diagnostic Method for Endometrial Endometrioid Carcinoma

Introduction: We aimed to determine the utility of Pipet Curet cytology (PCC) and Pipet Curet biopsy (PCB) for diagnosing uterine endometrial endometrioid carcinoma (EEC). Methods: We divided 77 patients with EEC into two groups per Federation of Gynecology and Obstetrics (FIGO) grades: G1 (n = 44) and G2/3 (n = 33) and compared the diagnostic sensitivity of PCC, PCB, and PCC and PCB combined, retrospectively. Next, we investigated any diagnostic discordance between PCC-based and PCB-based diagnoses per FIGO grade group. Results: The diagnostic sensitivity of PCC, PCB, and the two modalities combined was significantly higher for G2/3 EECs than for G1 EECs (72.7% vs. 45.5%, p = 0.0209; 84.8% vs. 63.6%, p = 0.0434; and 93.9% vs. 65.9%, p = 0.0046, respectively), likely due to more friable cancer cells in higher grade EEC cases. Among our 77 EEC patients, there were 4 patients (5.19%) with PCC-based concordant but PCB-based discordant results against EEC, in the G2/3 group predominantly. Diagnostic sensitivity of all cases increased from 72.7% (56/77) by PCB alone to 77.9% (60/77) by use of both modalities combined. Conclusion: Cytologic evaluation can reduce the number of false-negative histologic diagnoses. By providing complementary information, the two modalities combined from the Pipet Curet procedure would be valuable as a diagnostic method for EEC.

Role of Fyn expression in predicting the sensitivity to platinum‑based chemotherapy in patients with ovarian serous carcinoma.

Ovarian serous carcinoma is a gynecological malignancy associated with a high mortality rate, which is commonly diagnosed in the first instance at a late stage and has a propensity to develop resistance to platinum-based chemotherapy. Identifying reliable biomarkers for platinum sensitivity is critical for improving patient outcomes. The present retrospective study included 64 patients with high-grade serous ovarian carcinoma (Federation of Gynecology and Obstetrics stages III or IV). Patients were classified as platinum-sensitive (no relapse within 6 months of the last platinum administration) or platinum-resistant (relapse within 6 months). Immunohistochemical analysis was performed to evaluate Fyn expression in tumor tissues, and Fyn knockdown experiments were performed using the OVSAHO ovarian cancer cell line to assess carboplatin sensitivity. Fyn expression was significantly higher in platinum-resistant patients compared with in platinum-sensitive patients (P<0.01). A weighted Fyn expression score was developed and a cutoff score of 6 was determined to predict platinum sensitivity with a specificity of 65.5% and a sensitivity of 62.9%. Patients with low Fyn expression (score ≤6) exhibited higher platinum sensitivity and longer overall survival (P<0.05). Multivariate analysis identified Fyn expression and postoperative residual tumor size as independent predictors of platinum sensitivity (P=0.033 and P=0.023, respectively). In vitro, Fyn knockdown significantly increased carboplatin sensitivity in ovarian cancer cells (P<0.05). Fyn, a member of the Src family of kinases, serves a crucial role in various cellular functions and has been implicated in chemotherapy resistance. The results demonstrated a notable association between Fyn expression and platinum sensitivity in ovarian serous carcinoma. The findings suggested that Fyn may serve as a predictive biomarker for response to platinum-based chemotherapy, offering the potential for more personalized treatment strategies. To the best of our knowledge, the present study is the first to establish an association between Fyn expression and platinum sensitivity in advanced ovarian serous carcinoma. Prospective studies with larger, multi-center cohorts and comprehensive biomarker analyses are recommended to validate and extend these results, ultimately improving therapeutic strategies and patient prognosis.

Assessing the Adequacy of Traditional Vertebral Landmarks as Upper Border of Whole Pelvic Radiotherapy Field for Stage IB2-IIB Cervical Cancer.

This study investigates the impact of insufficient common iliac lymph node (CIN) irradiation on treatment outcomes in patients with stage IB2-IIB cervical cancer receiving concurrent chemoradiotherapy (CCRT). We retrospectively analyzed 68 patients with Federation of Gynecology and Obstetrics stage IB2-IIB, treated with weekly cisplatin-based CCRT from 2008 to 2018. Patients received external-beam whole pelvic radiotherapy (WPRT) and concurrent cisplatin chemotherapy, followed by high-dose-rate brachytherapy. The WPRT upper border was at L4-5 in 61 patients and L3-4 in 7 patients. Thirty-seven patients had the CIN area fully included (full-CIN group), while 31 had partial inclusion (partial-CIN group). Recurrence rates and survival outcomes were analyzed over a median follow-up of 111 months. Patient characteristics and the irradiated dose were comparable. Treatment failure occurred in three patients (8.1%) in the full-CIN group and in six patients (19.4%) in the partial-CIN group, with CIN and para-aortic lymph node recurrence in two and one patients, respectively. The 5-year cumulative recurrence rate was 0% for the full-CIN group and 11.4% for the partial-CIN group (p = 0.04). Cause-specific survival was 100% vs. 87.1% (p = 0.025), and the overall survival was 94.3% vs. 87.1% (p = 0.44). Fully including the CIN area in WPRT is crucial for stage IB2-IIB cervical cancer. Vascular anatomical margins should be considered over vertebral landmarks.

The impact of Paclitaxel-based hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer patients - interim analysis of safety and immediate efficacy of a randomized control trial (C-HOC trial)

ObjectiveThis study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC, IVA and IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of the planned trial (C-HOC Trial).MethodsIn a single-center, open-label, randomized control trial, FIGO stage IIIC, IVA, and IVB HGSOC patients (FAGOTTI score ≥ 8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The Experiment Group (HIPEC Group) received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the Control Group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). The adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS were compared.ResultsAmong 65 enrolled patients, 39 HIPEC Group and 21 Control Group patients underwent IDS. Grade 3–4 chemotherapy-related adverse effects were primarily hematological with no significant differences between the two groups. The HIPEC Group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P = 0.000). R0 resection rates in IDS were 69.2% (HIPEC Group) and 66.7% (Control Group). R2 resection occurred in 2.6% (HIPEC Group) and 14.3% (Control Group) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively.ConclusionsCombining HIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. HIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if HIPEC combined with IV NACT is superior to IV NACT alone.

New online dynamic nomograms to predict recurrence-free and overall survival after resection of endometrial cancer: a single-institution retrospective cohort study

PurposeThe significant global burden of endometrial cancer (EC) and the challenges associated with predicting EC recurrence indicate the need for a dynamic prediction model. This study aimed to propose nomograms based on clinicopathological variables to predict recurrence-free survival (RFS) and overall survival (OS) after surgical resection for EC.MethodsThis single-institution retrospective cohort study included patients who underwent surgical resection for EC. Web-based nomograms were developed to predict RFS and OS following resection for EC, and their discriminative and calibration abilities were assessed.ResultsThis study included 289 patients (median age, 56 years). At a median follow-up of 51.1 (range, 4.1–128.3) months, 13.5% (39/289) of patients showed relapse or died, and 10.7% (31/289) had non-endometrioid tumors (median size: 2.8 cm). Positive peritoneal cytology result (hazard ratio [HR], 35.06; 95% confidence interval [CI], 1.12–1095.64; P = 0.0428), age-adjusted Charlson comorbidity index (AACCI) (HR, 52.08; 95% CI, 12.35–219.61; P < 0.001), and FIGO (Federation of Gynecology and Obstetrics) stage IV (HR, 138.33; 95% CI, 17.38–1101.05; P < 0.001) were predictors of RFS. Similarly, depth of myometrial invasion ≥ 1/2 (HR, 1; 95% CI, 0.46–2.19; P = 0.995), AACCI (HR, 93.63; 95% CI, 14.87–589.44; P < 0.001), and FIGO stage IV (HR, 608.26; 95% CI, 73.41–5039.66; P < 0.001) were predictors of OS. The nomograms showed good predictive capability, positive discriminative ability, and calibration (RFS: 0.895 and OS: 0.891).ConclusionThe nomograms performed well in internal validation when patients were stratified into prognostic groups, offering a personalized approach for risk stratification and treatment decision-making.

Prognostic significance of pyroptosis-associated molecules in endometrial cancer: a comprehensive immunohistochemical analysis.

Endometrial cancer, the most prevalent malignancy of the female genital tract, has a concerningly poor prognosis when diagnosed in advanced stages, with limited targeted therapy options available for advanced or recurrent cases. Pyroptosis, a type of nonapoptotic cell death mediated by caspase-1, has shown potential antitumor effects in various tumors. NLRP3, a cytosolic sensor, initiates the canonical pyroptotic pathway, leading to caspase-1 activation, subsequent gasdermin D cleavage, and plasma membrane pore formation. The ESCRT-III machinery, particularly CHMP4B, acts as a key inhibitor of pyroptosis by repairing gasdermin D-induced membrane damage. The current study aimed to evaluate the clinicopathologic relevance of key pyroptosis-associated molecules in endometrial cancer. Immunohistochemistry was used to assess the expression of four pyroptosis-associated molecules (NLRP3, cleaved caspase-1 p20, cleaved gasdermin D, and CHMP4B) in 351 patients with endometrial cancer, and their associations with clinical, pathological, and survival outcomes were analyzed. High NLRP3 expression was significantly associated with age ≤ 50 years and premenopause. Increased cleaved caspase-1 p20 expression was associated with nonendometrioid carcinoma, Federation of Gynaecology and Obstetrics (FIGO) grade 3, and the p53 mutant pattern and was independently associated with poor recurrence-free survival (RFS) and overall survival. Increased cleaved gasdermin D expression was associated with a body mass index of >25 kg/m², FIGO grades 1-2, early FIGO stage (I-II), and absence of lymph node metastasis. High CHMP4B expression was associated with nonendometrioid carcinoma and poor RFS. Cleaved gasdermin D-high/CHMP4B-low endometrial cancer was associated with endometrioid carcinoma, FIGO grades 1-2 and favorable RFS. Our study identified cleaved caspase-1 p20 as an independent predictor of adverse outcomes in endometrial cancer. CHMP4B, an inhibitor of pyroptosis, was associated with an unfavorable RFS, whereas high cleaved gasdermin D/low CHMP4B expression was associated with a favorable RFS. These findings underscore the prognostic significance of pyroptosis and the potential interaction between cleaved gasdermin D and CHMP4B in endometrial cancer.

Redox Biomarkers and Matrix Remodeling Molecules in Ovarian Cancer.

Ovarian cancer (OC) has emerged as the leading cause of death due to gynecological malignancies among women. Oxidative stress and metalloproteinases (MMPs) have been shown to influence signaling pathways and afflict the progression of carcinogenesis. Therefore, the assessment of matrix-remodeling and oxidative stress intensity can determine the degree of cellular injury and often the severity of redox-mediated chemoresistance. The study group comprised 27 patients with serous OC of which 18% were classified as Federation of Gynecology and Obstetrics (FIGO) stages I/II, while the rest were diagnosed grades III/IV. The control group comprised of 15 ovarian tissue samples. The results were compared with genetic data from The Cancer Genome Atlas. Nitro-oxidative stress, inflammation and apoptosis biomarkers were measured colorimetrically/fluorometrically or via real-time PCR in the primary ovarian tumor and healthy tissue. Stratification of patients according to FIGO stages revealed that high-grade carcinoma exhibited substantial alterations in redox balance, including the accumulation of protein glycoxidation and lipid peroxidation products. TCGA data demonstrated only limited prognostic usefulness of the studied genes. In conclusion, high-grade serous OC is associated with enhanced tissue oxidative/nitrosative stress and macromolecule damage that could not be overridden by the simultaneously augmented measures of antioxidant defense. Therefore, it can be assumed that tumor cells acquire adaptive mechanisms that enable them to withstand the potential toxic effects of elevated reactive oxygen species.

Radiotherapy can improve overall survival in patients with lymph-node positive, high-grade neuroendocrine cervical cancer: construction of two prognostic nomograms to predict treatment outcome.

To explore the beneficial subgroups after radiotherapy in high-grade neuroendocrine cervical cancer (HGNECC) and construct two survival prognosis models to quantify the efficacy of radiotherapy assessment. In this retrospective study, we included 592 eligible samples from the Surveillance, Epidemiology, and End Results (SEER) database and 56 patients with lymph-node positive HGNECC from Chongqing Medical University. Cox regression analysis was used to identify independent survival prognosis risk factors for HGNECC patients. Propensity score matching (PSM) was employed as it balances the baseline differences among grouping methods. Kaplan-Meier (K-M) curves were used to analyze survival differences among different groups. Two survival prediction nomograms were constructed separately (using the "rms" package in R software) based on whether radiotherapy was administered. The stability and accuracy of these models were assessed using receiver operating characteristic (ROC) curves and calibration curves in both the training and validation datasets. P<0.05 was considered to indicate statistically significant differences. Age, Federation of Gynecology and Obstetrics (FIGO)-stage, and treatment methods (surgery vs. chemotherapy) were independent risk factors that affected survival prognosis (P<0.05). Radiotherapy showed adverse effects on survival in patients with early tumor staging, lymph-node negative status, and absence of distant metastasis (all P<0.05). The lymph-node positive group had a beneficial response to radiotherapy (P<0.05), and patients with metastasis in the radiotherapy group showed a survival protection trend (P=0.069). In HGNECC, patients with lymph-node positive status can benefit from radiotherapy in terms of survival outcomes. We constructed two survival prediction models based on whether radiotherapy was administered, thereby offering a more scientifically guided approach to clinical treatment planning by quantifying the radiotherapy efficacy.

Lymph node ratio as an indicator of nodal status in the assessment of survival and recurrence in vulvar cancer: A cohort study.

Inguinal lymph node (LN) metastasis and particularly the number of metastatic lymph nodes (NMLN) represent a determinant prognostic factor in vulvar squamous cell carcinoma (VSCC). However, the NMLN may be related to the number of removed LNs. Therefore, the lymph node ratio (LNR) reflects not only the burden of LN involvement but also the quality and extent of lymphadenectomy. To investigate the value of the LNR and the count of LN on overall survival (OS) and recurrence-free survival (RFS). This study is a retrospective, longitudinal, institution-based study. This study included 192 patients treated for VSCC at the Salah Azaiez Institute between 1994 and 2022. Clinical, pathological, and evolutionary data were reported. Survival curves were generated by the Kaplan-Meier method, and predictive factors of outcome were analyzed using Cox proportional hazards models. Surgery consisted of a radical vulvectomy, hemivulvectomy, and pelvic exenteration in, respectively, 96.4%, 2.1%, and 1.6% of cases followed by adjuvant radiotherapy in 38.5% of cases. LN dissection was bilateral in 88.5% of cases. LNR = 0, LNR = 0-0.2, and LNR ⩾0.2 were recorded in, respectively, 64.7%, 22.1%, and 13.2% of cases. With a mean follow-up time of 35 ± 42.06 months, the 5-year OS was 52.5% and the 5-year RFS was 55.8%. On multivariate analysis, the independent prognostic factors of OS were the LNR (hazard ratio (HR) = 5.702; 95% confidence interval (CI) = 2.282-14.245; p < 0.0001), Federation of Gynecology and Obstetrics (FIGO) stage (HR = 2.089; 95% CI = 1.028-4.277; p = 0.042), and free margins (HR = 2.247; 95% CI = 1.215-4.155; p = 0.01). Recurrences were recorded in 37.5% of cases. Independent prognostic factors of RFS were the LNR (HR = 2.911; 95% CI = 1.468-5.779; p = 0.002), FIGO stage (HR = 1.835; 95% CI = 1.071-3.141; p = 0.027), and free margins (HR = 2.091; 95% CI = 1.286-3.999; p = 0.003). Surgical margin, FIGO stage, and LNR represent the independent prognostic factors of survival and LNR showed superior prognostic predictive accuracy compared with the revised 2021 FIGO staging system for predicting OS and RFS in VSCC.

Association Between Germline BRCA1/2 Gene Variants and Clinicopathological Features of Ovarian Cancer.

To investigate the relationship between BRCA1/2 gene mutation and clinicopathological features in ovarian cancer patients, so as to develop precise individualized treatment plan for patients. Patients diagnosed with ovarian cancer between January 2018 and July 2023 who underwent BRCA1/2 genetic testing were retrospectively analyzed. The clinicopathological characteristics (age, body mass index (BMI), family history of ovarian cancer, pregnancy history, menopause status, tumor size, histopathology, Federation of Gynecology and Obstetrics (FIGO) staging, and ascites) of non-carriers and BRCA1/2 variant carriers were compared. Logistic regression analysis was used to explore the relationship between BRCA1/2 variants and clinicopathological characteristics of ovarian cancer. A total of 284 ovarian cancer patients were collected, and the subjects were divided into two groups, 197 non-carriers and 87 BRCA1/2 variants carriers. The proportion of serous ovarian carcinoma in BRCA1/2 variant carriers is higher than that in non-BRCA variant carriers (78.2% vs 60.9%, p=0.015). There were 51 patients with BRCA pathogenic or likely pathogenic variant, 22 patients with BRCA likely benign variant, and 14 patients with BRCA variants of uncertain significance (VUS). The proportion of serous ovarian carcinoma in patients with BRCA pathogenic/likely pathogenic variant is higher than that in patients with BRCA likely benign variant and BRCA VUS (94.1% vs 50.0% and 64.3%. p<0.001). There were no statistically significant differences in BMI, family history of ovarian cancer, pregnancy history, menopause status, maximum diameter of the tumor lesion, FIGO stage, and ascites among patients with different grades of variants. Multivariate logistic regression analysis showed that serous ovarian carcinoma was related to BRCA mutation (Serous carcinoma vs non-serous carcinoma: OR 2.145, 95% CI: 1.044-4.407) (p=0.038). Patients with BRCA1 variant develop ovarian cancer at a younger age than those with the BRCA2 variant. The proportion of FIGO stage III-IV in patients with BRCA pathogenic + likely pathogenic variant was significantly higher than those in patients with other variants. Germline BRCA1/2 variants were most frequently identified in serous ovarian carcinoma patients.

Investigating the influence of primary uterine tumor site on pelvic and para-aortic lymph node metastatic pattern and evaluating the risk factors for lymph node metastases in endometrial carcinoma: A retrospective study.

To assess the metastatic pattern in pelvic and para-aortic lymph nodes in relation with the primary uterine tumor site and to evaluate risk factors for lymph node metastases. 212 patients with endometrial cancer who underwent surgical treatment from December 2014 to December 2019 were selected. The clinical and pathological data were retrospectively analyzed. The factors and uterine primary tumor site related to lymph node metastasis were analyzed by univariate and multivariate analysis. Among the 212 patients with endometrial cancer, 17 cases had lymph node metastasis, and thus the metastasis rate was 8.02%. Univariate analysis revealed that lymph node metastasis was significantly correlated with Federation of Gynecology and Obstetrics stage, depth of myometrial invasion, tumor size, pathological grade, and lymphovascular space invasion (P < .05) and was not correlated with age, pathological type, and cervical involvement (P > .05). Primary uterine tumor site (fundus, horns, body or lower uterine segment) with or without cervical involvement was associated with different lymph nodes' metastatic sites. The lymph node metastatic pathways of endometrial cancer mainly include obturator lymph nodes and para-aortic lymph nodes, and skip metastasis may occur; endometrial carcinoma may jump and metastasize to para-aortic lymph nodes, specially when the lesion is located in the uterine fundus and uterine horns (cornua of uterus); there is a significant correlation between the location of lymph node metastasis and the location of primary uterine malignant tumor.

Prognostic Factors and a Predictive Nomogram of Cancer-Specific Survival of Epithelial Ovarian Cancer Patients with Pelvic Exenteration Treatment.

The aim of this study was to explore prognostic factors, develop and internally validate a prognostic nomogram model, and predict the cancer-specific survival (CCS) of epithelial ovarian cancer (EOC) patients with pelvic exenteration (PE) treatment. A total of 454 EOC patients from the Surveillance, Epidemiology, and End Results (SEER) database were collected according to the inclusion criteria and randomly divided into the training (n = 317) and validation (n = 137) cohorts. Prognostic factors of EOC patients with PE treatment were explored by univariate and multivariate stepwise Cox regression analyses. A predictive nomogram was constructed based on selected risk factors. The predictive power of the constructed nomogram was assessed by the time-dependent receiver operating characteristic (ROC) curve. Kaplan-Meier (KM) curve stratified by patients' nomoscore was also plotted to assess the risk stratification of the established nomogram. In internal validation, the C index, calibration curve, and decision curve analysis (DCA) were employed to assess the discrimination, calibration, and clinical utility of the models, respectively. In the training cohort, age, histological type, Federation of Gynecology and Obstetrics (FIGO) stage, number of examined lymph nodes, and number of positive lymph nodes were found to be independent prognostic factors of postoperative CSS. A practical nomogram model of EOC patients with PE treatment was constructed based on these selected risk factors. Time-dependent ROC curves and KM curves showed the superior predictive capability and excellent clinical stratification of the nomogram in both training and validation cohorts. In the internal validation, the C index, calibration plots, and DCA in the training and validation cohorts confirmed that the nomogram presents a high level of prediction accuracy and clinical applicability. Our nomogram exhibited satisfactory survival prediction and prognostic discrimination. It is a user-friendly tool with high clinical pragmatism for estimating prognosis and guiding the long-term management of EOC patients with PE treatment.

Neoadjuvant chemotherapy followed by interval debulking surgery for advanced epithelial ovarian cancer: GOTIC-019 study

IntroductionThree randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice.Patients and methodsWe conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III–IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy.ResultsPatients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99–1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80–1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74–1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65–1.47, p = 0.93).ConclusionsNAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS.

Correlation of INHBA Overexpression with Pathological Features, Antitumor Immune Response and Clinical Prognosis in Cervical Cancer

Background and Objectives: Cervical cancer (CC) is a malignant tumor occurring in the cervical epithelium, which is one of the most common cancer-caused deaths in females. Inhibin β A (INHBA) is the most widely expressed biomarker of the transforming growth factor-β (TGF-β) family in tumor cells, and has predictive value for tumor development and prognosis. In this study, the expression of INHBA in CC tissue was examined to analyze the relationship between INHBA expression and pathological characteristics, anti-tumor immune response and clinical prognosis of CC. In addition, the factors affecting the prognosis of CC patients were explored. Materials and Methods: 84 patients with CC, who underwent surgical resection in our hospital from March 2016 to August 2017, were retrospectively picked. The tumor tissues and normal adjacent tissues of patients with CC were collected, and the expression of INHBA in CC tissues and adjacent tissues was detected using immunohistochemistry (IHC). The relationship between INHBA expression and clinicopathological characteristics of CC patients was analyzed. The relationship between INHBA expression and clinical prognosis was analyzed using the Kaplan-Meier (K-M) survival curve. The levels of anti-tumor immune-response-related factors (interferon-γ (IFN-γ), interleukin-10 (IL-10), tumor necrosis factor- α (TNF-α) and IL-2) were evaluated in patients with negative and positive expressions of INHBA. The patients were followed up for 60 months and were graded as a good prognosis group and poor prognosis group according to whether the patients died or had recurrence and metastasis. Relevant factors affecting the prognosis of the patients were analyzed. Results: INHBA was localized in the cytoplasm of cancer tissues. The positive expression rate in cancer tissues was 67.86%, which was much higher than the 28.57% in normal adjacent tissues (p < 0.05). Expression of INHBA was closely correlated with Federation of Gynecology and Obstetrics (FIGO) staging, differentiation and lymph node metastasis (p < 0.05). Compared with INHBA-negative expression group, the contents of IFN-γ, TNF-α and IL-2 were much lower, while the level of IL-10 was strongly elevated in the INHBA-positive expression group (p < 0.01). Eighty-four patients with CC were followed up for 36 months. The K-M survival curve showed that the patients with a positive expression of INHBA had a significantly shorter survival period than the patients with a negative expression of INHBA (p < 0.05). There were significant differences in FIGO staging, differentiation, lymph node metastasis and INHBA expression between patients with a good prognosis and poor prognosis (p < 0.05). Logistic regression analysis showed that FIGO stage, differentiation degree, lymph node metastasis and INHBA were the factors influencing the poor prognosis of patients with CC (p < 0.05). Conclusion: The abnormally high expression of INHBA in patients with CC was related to the pathological characteristics, anti-tumor immune response and survival time, and leaded to a poor prognosis. It was speculated that INHBA exerted an important reference role in tumor invasion and clinical prognosis evaluation, which could act as a new target for anti-tumor treatment of CC.

Immunoexpression of p53 and p16 in Low and High-grade Serous Ovarian Cancer: A Cross-sectional Study

Introduction: The most common malignancy of the ovary is serous carcinoma, which can be classified as either Low-grade Serous Ovarian Carcinoma (LGSOC) or High-grade Serous Ovarian Carcinoma (HGSOC) and originates from the surface epithelium. However, the overall prognosis for both cancers is very poor. Immunohistochemical analysis of p53 and p16 expression is commonly used to detect mutations. Diffuse and strong mutations (mutant type) are almost always observed in cases of HGSOC, while focal expression (wild type) suggests the absence of mutations in HGSOC. LGSOCs are characterised by a low number or absence of genetic mutations. Aim: To investigate the association between p53 and p16 expression in different grades and stages of Serous Ovarian Carcinoma (SOC). Materials and Methods: This observational cross-sectional descriptive study was conducted on 62 patients diagnosed with ovarian serous carcinoma. The study focused on examining the expressions of p53 and p16 using Immunohistochemistry (IHC) in the Department of Pathology, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India, over a period of one and a half years (February 2021 to July 2022). The study parameters included clinical features, histological findings, staging, The Federation of Gynaecology and Obstetrics (FIGO), grading, p53 and p16 expression by IHC in all cases, and the association between p53 and p16 expression with the grade and stage of the cancer. Statistical analysis was performed using Analysis of Variance (ANOVA) and Statistical Package for Social Sciences (SPSS) software. A p-value of less than 0.05 was considered significant. Results: A total of 62 cases were included in the study, with 55 cases (88.70%) classified as LGSOC and 7 cases (11.29%) as HGSOC. The mean age for LGSOC was 53.5 years, while for HGSOC it was 54 years. Among the HGSOC cases (n=55), 45 cases (81.80%) showed diffuse positive results (mutant type) for p53. In contrast, there was no diffuse p53 expression in LGSOC cases (n=7), with 5 cases (71.40%) showing focal positivity (wild type). The p-value for comparing p53 expression in both cases was significant (&lt;0.00001). As for p16 expression, among the HGSOC cases (n=55), 31 cases (56.40%) showed diffuse positivity (mutant type), while among the LGSOC cases (n=7), most of the cases, 5 cases (71.40%), showed focal positivity (wild type). The p-value for comparing p16 expression in both cases was significant (&lt;0.003794). Conclusion: In conclusion, p53 along with p16 are good markers for grading SOC, and p53 is highly effective in differentiating HGSOC from LGSOC based on the positivity pattern (diffuse and strong positive for high-grade/mutant type, and focal positive for low-grade cancers). Thus, p53 has become an attractive target for the development of moleculetargeted therapies for this disease.

Downregulation of HS6ST2 Inhibits Cervical Cancer Cell Migration and Invasion in Vivo and in Vitro.

Emerging evidence indicates the importance of heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) in a number of developmental processes. Little is known regarding its biological function in regulating cervical cancer (CC) progression. In this study, we aim to explore the role of HS6ST2 in CC progression. The transcriptome sequencing data of CC tissues from three databases, GSE64217, GSE138080, and GSE63514, was examined for genes with significant changes. The expression profile for HS6ST2 within CC tissue was then assessed through fluorescence quantitative PCR and immunohistochemistry and compared to data from patients with clinicopathological features. A multivariate survival analysis was performed using the COX regression. The real-time quantitative PCR assessed the HS6ST2 expression profile within CC cellular cultures. The results of knocking down HS6ST2, considering the proliferative activity and invasiveness of CC cultures in vitro, were detected through cell viability assay, clonogenic assessment, tumorsphere formation analysis, 3D invasion experiment and transwell assay. The impact of HS6ST2 knockdown in CC proliferation was also evaluated in vivo using a nude mice model. HS6ST2 was severely upregulated within CC tissues across the three explored databases (GSE64217, GSE138080, and GSE63514). Fluorescent quantitative PCR and immunohistochemistry experiments identified HS6ST2 as highly upregulated within patients CC tissues. Survival analysis taking into account the parameters of lymph node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, depth of invasion, pathological grade, and HS6ST2 expression level demonstrated that individuals with downregulated HS6ST2 exhibited considerably extended progression-free survival (PFS) and overall survival (OS) in comparison to upregulated HS6ST2 cases. According to the findings of COX univariate analysis, the parameters lymph node metastasis, FIGO stage, depth of invasion, pathological grade, and HS6ST2 expression level, all showed a statistically significant correlation with effect upon prognosis of CC patients. The FIGO stage, depth of invasion and expression level of HS6ST2 were identified as independent risk variables influencing CC case prognosis within subsequent COX multivariate analysis. Cell function experiments proved that HS6ST2 knockdown can considerably diminish the proliferative potential, stemness and invasive traits of CC cells. Tumor formation experiments in nude mice in vivo demonstrated that knocking down HS6ST2 can significantly thwart CC cellular proliferative properties within animal models. The clinicopathological features and the survival time of the patients significantly correlate with the level of HS6ST2 expression in CC tissue samples.

Serum Spondin-2 expression, tumor invasion, and antitumor immune response in patients with cervical cancer.

Cervical cancer is a gynecological malignancy common in middle-aged and older patients, with a high mortality rate. Spondin-2 is an extracellular matrix protein that involved in innate and acquired immune responses. Herein, we investigated the relationship between serum Spondin-2 expression, tumor invasion and infiltration, and immune response in patients with cervical cancer and provided a theoretical basis for clinical practice. To investigate the relationship between serum Spondin-2 expression and cervical cancer-related indicators. Overall, 147 patients with cervical cancer who were admitted to our institution between January 2019 and August 2019 were assigned to the cervical cancer group, and 92 patients with benign uterine lesions and 86 healthy individuals were assigned to the benign and control groups, respectively. In each group, serum Spondin-2 expression was measured, and the receiver operating characteristic (ROC) curve was determined. Patients with cervical cancer were classified into high or low Spondin-2 groups depending on the Spondin-2 threshold value used for diagnosing cervical cancer. Patient's clinical data were collected to compare the clinicopathologic characteristics, immune cytokine levels, and prognosis of patients with varying Spondin-2 expression levels. The expression level of serum Spondin-2 was significantly higher in the cervical cancer group than in the benign and control groups (P < 0.05). According to the ROC curve, the cutoff value of Spondin-2 used in the diagnosis of cervical carcinoma was 25.68 ± 7.11 μg/L. The proportion of patients with Federation of Gynecology and Obstetrics stage III, nerve invasion, vascular invasion, and lymph node metastasis was higher in the high Spondin-2 group than in the low Spondin-2 group (P < 0.05). Interleukin-5 (IL-5) and IL-4 Levels were higher in the high Spondin-2 group than in the low Spondin-2 group. In contrast, IL-2 and tumor necrosis factor-α levels were lower in the high Spondin-2 group than in the low Spondin-2 group (P < 0.05). After 3 years of follow-up, progression-free survival and overall survival were significantly shorter in the high Spondin-2 group than in the low Spondin-2 group (P < 0.05). The expression of serum Spondin-2 is upregulated in patients with cervical carcinoma and is related to tumor invasion and infiltration, antitumor immune response, and prognosis.

Invisible cervical cancers on MRI: Can the type of histology (SCC versus non-SCC) influence surgical planning?

Invisible cervical cancers on MRI can indicate less invasive surgery. Cervical cancers consist of squamous cell carcinoma (SCC) and non-SCC, each with different long-term outcomes. It is still unclear if surgical planning should be changed according to the histologic type of cervical cancer when it is not visible on MRI. The purpose of the study was to determine if surgical planning for cervical cancer that is not visible on MRI is influenced by the histologic type. Between January 2007 and December 2016, 155 women had Federation of Gynecology and Obstetrics (FIGO) stage 1B1 cervical cancer that was not visible on preoperative MRI. They underwent radical hysterectomies and pelvic lymph node dissections. Among them, 88 and 67 were histologically diagnosed with SCC and non-SCC, respectively. The size of the residual tumor, depth of stromal invasion, parametrial invasion, vaginal invasion, lymphovascular invasion, and lymph node metastasis were compared between these patients using the t-test, Mann-Whitney U test, Chi-squared test, or Fisher's exact test. The recurrence-free and overall 10-year survival rates were compared between the groups by Kaplan-Meier analysis. The mean sizes of residual tumors were 8.4 ± 10.4mm in the SCC group and 12.5 ± 11.9mm in the non-SCC group (p = 0.024). The mean depth of stromal invasion in the SCC group was 12.4 ± 21.2% (0%-100%), whereas that in the non-SCC group was 22.4 ± 24.4 (0%-93%) (p = 0.016). However, there was no difference in parametrial or vaginal invasion, lymphovascular invasion, or lymph node metastasis (p = 0.504-1.000). The recurrence-free and overall 10-year survival rates were 98.9% (87/88) and 95.5% (64/67) (p = 0.246), and 96.6% (85/88) and 95.5% (64/67) (p = 0.872), respectively. The non-SCC group tends to have larger residual tumors and a greater depth of stromal invasion than the SCC group, even though neither is visible on MRI. Therefore, meticulous care is necessary for performing parametrectomy in patients with non-SCC cervical cancer.