Mechanisms of carboplatin- and paclitaxel-dependent induction of premature senescence and pro-cancerogenic conversion of normal peritoneal mesothelium and fibroblasts.

Carboplatin (CPT) and paclitaxel (PCT) are the optimal non-surgical treatment of epithelial ovarian cancer (EOC). Although their growth-restricting influence on EOC cells is well known, their impact on normal peritoneal cells, including mesothelium (PMCs) and fibroblasts (PFBs), is poorly understood. Here, we investigated whether, and if so, by what mechanism, CPT and PCT induce senescence of omental PMCs and PFBs. In addition, we tested whether PMC and PFB exposure to the drugs promotes the development of a pro-cancerogenic phenotype. The results showed that CPT and PCT induce G2/M growth arrest-associated senescence of normal peritoneal cells and that the strongest induction occurs when the drugs act together. PMCs senesce telomere-independently with an elevated p16 level and via activation of AKT and STAT3. In PFBs, telomeres shorten along with an induction of p21 and p53, and their senescence proceeds via the activation of ERK1/2. Oxidative stress in CPT + PCT-treated PMCs and PFBs is extensive and contributes causatively to their premature senescence. Both PMCs and PFBs exposed to CPT + PCT fuel the proliferation, migration, and invasion of established (A2780, OVCAR-3, SKOV-3) and primary EOCs, and this activity is linked with an overproduction of multiple cytokines altering the cancer cell transcriptome and controlled by p38 MAPK, NF-κB, STAT3, Notch1, and JAK1. Collectively, our findings indicate that CPT and PCT lead to iatrogenic senescence of normal peritoneal cells, which paradoxically and opposing therapeutic needs alters their phenotype towards pro-cancerogenic. It cannot be excluded that these adverse outcomes of chemotherapy may contribute to EOC relapse in the case of incomplete tumor eradication and residual disease initiation. © 2023 The Pathological Society of Great Britain and Ireland.

The Prognostic Value of Cancer Stem Cell Markers (CSCs) Expression-ALDH1A1, CD133, CD44-For Survival and Long-Term Follow-Up of Ovarian Cancer Patients.

Recurrent disease and treatment-associated chemoresistance are the two main factors accounting for poor clinical outcomes of ovarian cancer (OC) patients. Both can be associated with cancer stem cells (CSCs), which contribute to cancer formation, progression, chemoresistance, and recurrence. Hence, this study investigated whether the expression of known CSC-associated markers ALDH1A, CD44, and CD133 may predict OC patient prognosis. We analyzed their expression in primary epithelial ovarian cancer (EOC) patients using immunohistochemistry and related them to clinicopathological data, including overall survival (OS) and progression-free survival (PFS). Expression of ALDH1A1 was detected in 32%, CD133 in 28%, and CD44 in 33% of cases. While Kaplan-Meier analysis revealed no association of the expression of CD133 and CD44 with PFS and OS, ALDH1A1-positive patients were characterized with both significantly shorter OS (p = 0.00022) and PFS (p = 0.027). Multivariate analysis demonstrated that the expression of ALDH1A1, FIGO stage III-IV, and residual disease after suboptimal debulking or neoadjuvant chemotherapy correlated with shorter OS. The results of this study identify ALDH1A1 as a potential independent prognostic factor of shorter OS and PFS in EOC patients. Therefore, targeting ALDH1A1-positive cancer cells may be a promising therapeutic strategy to influence the disease course and treatment response.

Cancer Stem Cell Markers-Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis.

Cancer stem cells (CSCs) may contribute to an increased risk of recurrence in ovarian cancer (OC). Further research is needed to identify associations between CSC markers and OC patients' clinical outcomes with greater certainty. If they prove to be correct, in the future, the CSC markers can be used to help predict survival and indicate new therapeutic targets. This study aimed to determine the CSC markers at mRNA and protein levels and their association with clinical presentation, outcome, and risk of recurrence in HGSOC (High-Grade Serous Ovarian Cancer). TCGA (The Cancer Genome Atlas) database with 558 ovarian cancer tumor samples was used for the evaluation of 13 CSC markers (ALDH1A1, CD44, EPCAM, KIT, LGR5, NES, NOTCH3, POU5F1, PROM1, PTTG1, ROR1, SOX9, and THY1). Data on mRNA and protein levels assessed by microarray and mass spectrometry were retrieved from TCGA. Models to predict chemotherapy response and survival were built using multiple variables, including epidemiological data, expression levels, and machine learning methodology. ALDH1A1 and LGR5 mRNA expressions indicated a higher platinum sensitivity (p = 3.50 × 10-3; p = 0.01, respectively). POU5F1 mRNA expression marked platinum-resistant tumors (p = 9.43 × 10-3). CD44 and EPCAM mRNA expression correlated with longer overall survival (OS) (p = 0.043; p = 0.039, respectively). THY1 mRNA and protein levels were associated with worse OS (p = 0.019; p = 0.015, respectively). Disease-free survival (DFS) was positively affected by EPCAM (p = 0.004), LGR5 (p = 0.018), and CD44 (p = 0.012). In the multivariate model based on CSC marker expression, the high-risk group had 9.1 months longer median overall survival than the low-risk group (p < 0.001). ALDH1A1, CD44, EPCAM, LGR5, POU5F1, and THY1 levels in OC may be used as prognostic factors for the primary outcome and help predict the treatment response.

An analysis of the significance of the lymph node ratio and extracapsular involvement in the prognosis of endometrial cancer patients.

Introduction: The primary aim of our study was to analyse the impact of the lymph node ratio (LNR) and extracapsular involvement (ECI) on the prognosis of endometrial cancer (EC) patients. Material and methods: We carried out a retrospective analysis of 886 patients surgically treated for EC between 2000 and 2015. In the subgroup of patients with lymph node metastases (LNM), we evaluated the impact of the number and localization of the LNM, LNR, and ECI on patients' overall survival (OS). Results: In the group of patients with LNM, 0.3 was the optimal LNR cut-off for differentiating between short- and long-term survivors [HR = 2.94 (95% CI: 1.49-5.80)]. Patients with a LNR ≥ 0.3 had a significantly shorter OS period (35.0 months, range 0.2-175 months) compared to patients with a LNR < 0.3 [median OS - mOS, was 143, range 15-169 months; (p = 0.003]. We observed significant differences in the mOS of EC patients without LNM compared to patients with LNM, as well as those with both LNM and ECI (p < 0.0001). In the group of patients with LNM, we also found that a poorer prognosis depended on the extension of the primary tumour. Conclusions: Our results suggest that when LNM are found, the long-term outcomes of EC patients are worse in those who have a LNR ≥ 0.3, the presence of ECI, and a more advanced extension of the primary tumour.

Performance of Selected Models for Predicting Malignancy in Ovarian Tumors in Relation to the Degree of Diagnostic Uncertainty by Subjective Assessment With Ultrasound.

OBJECTIVES: The study's main aim was to evaluate the relationship between the performance of predictive models for differential diagnoses of ovarian tumors and levels of diagnostic confidence in subjective assessment (SA) with ultrasound. The second aim was to identify the parameters that differentiate between malignant and benign tumors among tumors initially diagnosed as uncertain by SA. METHODS: The study included 250 (55%) benign ovarian masses and 201 (45%) malignant tumors. According to ultrasound findings, the tumors were divided into 6 groups: certainly benign, probably benign, uncertain but benign, uncertain but malignant, probably malignant, and certainly malignant. The performance of the risk of malignancy index, International Ovarian Tumor Analysis assessment of different neoplasias in the adnexa model, and International Ovarian Tumor Analysis logistic regression model 2 was analyzed in subgroups as follows: SA-certain tumors (including certainly benign and certainly malignant) versus SA-probable tumors (probably benign and probably malignant) versus SA-uncertain tumors (uncertain but benign and uncertain but malignant). RESULTS: We found a progressive decrease in the performance of all models in association with the increased uncertainty in SA. The areas under the receiver operating characteristic curve for the risk of malignancy index, logistic regression model 2, and assessment of different neoplasias in the adnexa model decreased between the SA-certain and SA-uncertain groups by 20%, 28%, and 20%, respectively. The presence of solid parts and a high color score were the discriminatory features between uncertain but benign and uncertain but malignant tumors. CONCLUSIONS: Studies are needed that focus on the subgroup of ovarian tumors that are difficult to classify by SA. In cases of uncertain tumors by SA, the presence of solid components or a high color score should prompt a gynecologic oncology clinic referral.

Analysis of long-term outcomes in 44 patients following pelvic exenteration due to cervical cancer.

BACKGROUND: Pelvic exenteration (PE) may be associated with prolonged overall survival (OS) in selected patients with advanced or recurrent cervical cancer. However, the factors related to improved survival following PE are not clearly defined. The aim of this study was to perform a retrospective analysis of OS rates in a group of patients undergoing PE in order to identify the factors related to improved long-term outcomes. METHODS: Our study group consisted of 44 patients, including 21 squamous cell cancer (SCC) patients, 22 patients with adenocarcinomas (AC) of the cervix, and one patient with undifferentiated cervical carcinoma. The patients were categorized according to the type of surgery, namely, primary surgery (12 patients) or surgery due to cancer recurrence (32 patients). RESULTS: In the group of patients with recurrent cervical cancer, we found that improved OS correlated with the SCC histological type and the presence of vaginal fistula. The need for reoperation within 30 days and the presence of severe adverse events significantly worsened the prognosis. We found a non significant trend toward improved survival in those patients with tumor-free margins. Lymph node metastases, the initial stage of the disease, the time to recurrence, and a history of hysterectomy had no impact on patients' OS. In the group of patients undergoing primary PE, we observed a trend toward improved survival among those diagnosed with vaginal fistula. CONCLUSIONS: Pelvic exenteration seemed to improve the long-term outcomes for patients with SCC cancer recurrence and vaginal fistula whose surgery was unrelated to severe adverse events.

An Analysis of Long-Term Outcomes in Patients Treated by Extensive Bowel Resection Due to Advanced Ovarian Cancer Relative to the Effectiveness of Surgery.

INTRODUCTION: Surgery for advanced ovarian cancer (AOC) often requires bowel resections. However, the impact of bowel surgery on patient overall survival (OS) has not yet been precisely determined. OBJECTIVE: The aim of the study was to analyze the OS rates in a group of AOC patients undergoing bowel resection. METHODS: We carried out a retrospective analysis of patients who had undergone low anterior resection of the rectum (LAR) during primary or interval debulking surgery for AOC. We divided the patients into 2 groups: Group 1 included 69 patients who underwent only LAR; Group 2 included 66 patients who underwent LAR and additional bowel resection. The control group included 71 AOC patients who did not required bowel resection. RESULTS: In the subgroup of patients with no gross residual disease (NGR), there were no differences in OS between Groups 1 and 2. In the subgroup of "optimally" (tumors <1 cm) debulked patients, Group 1 patients had a higher median OS than Group 2 patients. Additionally, there was no difference between Groups 1 and 2 as far as the number of severe adverse events. CONCLUSIONS: Multiple bowel resections seem to improve OS in patients when NGR is achieved but should be avoided when complete resection is not possible.

High post-treatment serum soluble receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) levels is associated with poor survival of patients with cervical cancer.

AIM: Receptor-binding cancer antigen expressed on SiSo cells (sRCAS1) is responsible for induction of selective immunosuppression. In addition, preclinical studies have shown that sRCAS1 levels may reflect cancer aggressiveness. The main aim of our study was to analyze pre- and post-treatment levels of sRCAS1 in the sera of patients treated for cervical cancer and to evaluate whether the levels change during treatment and their impact on patient prognosis. METHODS: The study included 49 patients suffering from cervical cancer. The early stage cervical cancer patients (14) were treated surgically, while the advanced stage patients (35) underwent radiochemotherapy. Serum sRCAS1 levels were evaluated both before and after intervention with the use of the ELISA method. RESULTS: We have found that median serum sRCAS1 levels of patients before intervention were not significantly different from the levels assessed after intervention. There were also no differences when pre- and post-treatment levels were compared within the group of early and of advanced stage patients. Serum sRCAS1 levels were not influenced by either the histopathological type of the tumor or the methods of treatment. High post-intervention sRCAS1 levels indicated shortened OS when compared to low sRCAS1 levels. Neither pre-intervention sRCAS1 levels nor the alteration in sRCAS1 levels during treatment were associated with patient prognosis. In multivariate analysis, post-treatment sRCAS1 levels and clinical stage of cervical cancer remained as independent predictors of survival. CONCLUSION: High post-treatment serum sRCAS1 level in cervical cancer patients seems to be a negative prognostic factor for patient overall survival.

The association between lymph node metastases and long-term survival in patients with epithelial ovarian cancer.

INTRODUCTION: A key survival prognosis factor for patients treated for ovarian cancer is complete cytoreductive surgery where all macroscopic neoplastic implants, including enlarged metastatic lymph nodes, are removed. We presume that investigating the involvement of the lymphatic system can result in a more individualized approach to the treatment of ovarian cancer patients. The main aim of our study was to analyze the relationship between the presence, number and types of lymph node metastases and ovarian cancer patient prognosis. MATERIAL AND METHODS: We carried out a retrospective analysis of patients who underwent cytoreduction due to primary ovarian cancer, between 2010 and 2015. We analyzed the number of metastatic lymph nodes, the lymph node ratio defined as the ratio of the number of metastatic lymph nodes to the total number of lymph nodes removed, extracapsular involvement, and the histopathological pattern of metastases. RESULTS: The study group included 651 patients. Of these, 377 had lymphadenectomy, 144 presented with lymph node metastases, and 233 had no lymph node metastases. We also included a group of 274 patients who did not have lymphadenectomy. Patients with more than 4 metastatic lymph nodes and a lymph node ratio of ≥ 0.1 had significantly poorer overall survival. Extracapsular involvement had no relation to patient overall survival. Multivariant survival analysis indicated that a lymph node ratio of ≥ 0.1 was an independent predictor of poor survival. CONCLUSIONS: The analysis of lymph node metastases in ovarian cancer patients can have predictive value for patient overall survival.

High tumor cell vimentin expression indicates prolonged survival in patients with ovarian malignant tumors.

OBJECTIVES: The main aims of the study were to investigate the expression of vimentin and its correlation with the overall survival (OS) of patients with malignant ovarian tumors, and the correlation between vimentin expression and tumor stroma characteristics. MATERIAL AND METHODS: The study focused on 94 malignant ovarian tumors that had been collected from women who were treated in the Department of Gynecology and Oncology of the Lukaszczyk Oncological Center, Bydgoszcz, Poland. Vimentin expression was assessed in both the cancer cells (expression intensity and quantitative analysis) and the tumor stroma (expression intensity). Vimentin expression was analyzed according to both stromal cellularity and the clinicopatho- logical features of the disease. RESULTS: Both high cancer cell vimentin expression intensity and high quantitative vimentin expression (up to and includ- ing 30% of cells) indicated a significantly prolonged OS. Low vimentin stromal expression was associated with prolonged OS, although the difference did not reach the level of significance. High tumor cell vimentin expression intensity was as- sociated with significantly higher vimentin stromal expression. High vimentin expression in the tumor stroma indicated a significantly higher cellularity of the tumor stroma. Vimentin expression in cancer cells and the tumor stroma were not dependent on the histopathological type, the tumor grade or the FIGO stageof the disease. CONCLUSIONS: High cancer cell vimentin expression is associated with an improved OS of patients with malignant ovar- ian tumors. The expression of vimentin in ovarian malignancies may influence the structure of the tumor stroma.

The associations between serum VEGF, bFGF and endoglin levels with microvessel density and expression of proangiogenic factors in malignant and benign ovarian tumors.

AIM OF THE STUDY: To investigate whether serum levels of VEGF, bFGF and endoglin correlate with tumor VEGF and bFGF expression or microvessel density (MVD) in ovarian cancer. PATIENTS AND METHODS: Forty five patients with epithelial ovarian cancers (EOCs) and 38 patients with benign ovarian tumors (BOTs) were included into the study. Serum levels of VEGF, bFGF and endoglin were assessed using ELISA. The expression of VEGF and bFGF in tumor samples were evaluated using ELISA of supernatants obtained from tumor homogenization. MVD was analyzed using immunohistochemistry with antibodies against CD31, CD34 and CD105. RESULTS: Serum VEGF levels were significantly higher in EOCs than in BOTs (436.6pg/ml [19.67-2860] vs 295.5pg/ml [123-539], P=0.025). Serum endoglin levels were lowered in the group EOCs when compared to BOTs (33,720g/ml [12,220-73,940] vs 42,390pg/ml [19,380-56,910], P=0.015). There were no differences in bFGF levels between studied groups. EOCs have significantly higher CD105 MVD (25 vessels/mm2 [0-57] vs 6 vessels/mm2 [0-70], P<0.001) and tumor VEGF (405.9pg/mg protein [0-3000] vs 2.225 [0-634.7], P<0.001) expression than BOTs, while, bFGF expression was higher in BOTs than in EOCs (2076pg/mg protein [668.1-8718] vs 847.3pg/mg protein [188.9-8333], P=0.003). In patients with EOCs we have observed negative correlation between serum VEGF concentration and its tissue expression (r Spearman=-0.571, P=0.0261), and serum VEGF concentration correlated positively with CD34-MVD (r Spearman=0.545, P=0.0289). In a multiple regression analysis we have observed only the negative correlation between serum VEGF and CD105-MVD (r=-0.5288, P=0.0427). CONCLUSIONS: Serum VEGF is a useful marker for prediction of ovarian cancer MVD and tumor VEGF expression.

External validation of the IOTA ADNEX model performed by two independent gynecologic centers.

OBJECTIVES: The external, two-center validation of the IOTA ADNEX model for differential diagnosis of adnexal tumors. METHODS: A total of 204 patients with adnexal masses (134 benign and 70 malignant) treated at the Division of Gynecologic Surgery, Poznan University of Medical Sciences, Poland (Center I), and 123 patients (89 benign and 34 malignant) from the Department of Obstetrics and Gynecology, Clinica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain (Center II), were enrolled into the study. RESULTS: ADNEX achieved high accuracy in discriminating between malignant and benign ovarian tumors in both centers (79.9% and 81.3% in Centers I and II, respectively). Multiclass accuracy was substantially lower than in binary classification (malignant vs. benign): 64.2% and 74.0% in Centers I and II, respectively. Sensitivity and specificity for the diagnosis of specific tumor types in Center I were as follows: benign tumors - 72.4% and 94.3%; borderline tumors - 33.3% and 87.0%, stage I ovarian cancers - 00.0% and 91.8%; stage II-IV ovarian cancers - 68.2% and 83.1%; and metastatic tumors - 00.0% and 99.5%. Sensitivity and specificity in Center II were as follows: benign tumors - 75.3% and 97.1%; borderline tumors - 50.0% and 88.2%, stage I ovarian cancers - 40.0% and 97.5%; stage II-IV ovarian cancers - 95.0% and 88.3%; and metastatic tumors - 20.0% and 98.3%. CONCLUSIONS: ADNEX is characterized by very high accuracy in differentiating between malignant and benign adnexal tumors. However, prediction of ovarian tumor types could be more accurate.

Ultrasonographic features and CA125 levels of hormonally active ovarian tumors.

OBJECTIVES: Subjective ultrasonographic assessment is currently considered to be the best method of differentiation between various types of ovarian tumors. The aim of the study was to evaluate selected ultrasonographic features and CA125 levels of hormonally active ovarian tumors. MATERIAL AND METHODS: A total of 1135 women with ovarian tumors were diagnosed between 2006 and 2014 at the Division of Gynecologic Surgery, Poznan University of Medical Sciences. Within these tumors, there were 60 hormone-secreting ovarian tumors, including: 20 granulosa cell tumors, 28 fibrothecomas, 10 dysgerminomas, 2 struma ovarii, and 9 metastatic ovarian tumors. The tumors were evaluated by ultrasonography according to the International Ovarian Tumor Analysis group criteria. Additionally, we evaluated serum CA125 levels in all patients. RESULTS: Granulosa cell tumors occurred most frequently as large unilocular-solid cysts, moderately to highly vascularized, with low-resistance vascularization. Dysgerminomas were predominantly large unilocular-solid cysts or purely solid tumors, with minimal to moderate low-resistance vascularization. Fibrothecomas were solid masses with minimal, high-resistance vascularization. Struma ovarii occurred as small, solid masses with abundant, highresistance vascularization. Metastatic ovarian tumors presented mainly as multilocular-solid tumors with strong, low-resistance vascularization. Papillary projections were most frequently observed in metastatic tumors and granulosa cell tumors in 56% and 50% of the cases respectively, although only half of granulosa cell tumors papillary projections exceeded 3 mm. Elevated CA125 levels were found only in metastatic ovarian tumors. CONCLUSIONS: Hormonally active ovarian tumors present several ultrasonographic features which may facilitate preoperative diagnosis.

Menopausal status strongly influences the utility of predictive models in differential diagnosis of ovarian tumors: an external validation of selected diagnostic tools.

OBJECTIVES: The aim of this study was to externally validate the diagnostic performance of the International Ovarian Tumor Analysis logistic regression models (LR1 and LR2, 2005) and other popular prognostic models including the Timmerman logistic regression model (1999), the Alcazar model (2003), the risk of malignancy index (RMI, 1990), and the risk of malignancy algorithm (ROMA, 2009). We compared these models to subjective ultrasonographic assessment performed by an experienced ultrasonography specialist, and with our previously developed scales: the sonomorphologic index and the vascularization index. Furthermore, we evaluated diagnostic tests with regard to the menopausal status of patients. MATERIALS AND METHODS: This study included 268 patients with adnexal masses; 167 patients with benign ovarian tumors and 101 patients with malignant ovarian tumors were enrolled. All tumors were evaluated by using trans- vaginal ultrasonography according to the diagnostic criteria of the analyzed models. MATERIALS AND METHODS: This study included 268 patients with adnexal masses; 167 patients with benign ovarian tumors and 101 patients with malignant ovarian tumors were enrolled. All tumors were evaluated by using trans- vaginal ultrasonography according to the diagnostic criteria of the analyzed models. RESULTS: The subjective ultrasonographic assessment and all of the studied predictive models achieved similar diagnostic performance in the whole study population. However significant differences were observed when pre- and postmenopausal patients were analyzed separately In the subgroup of premenopausal patients, the highest area under the curve (AUC) was achieved by subjective ultrasonographic assessment (0.931), the Alcazar model (0.912), and LR1 (0.909). Alternatively in the group of postmenopausal patients, the highest AUC was noted for the Timmerman model (0.973), ROMA (0.951), and RMI (0.938). CONCLUSIONS: Menopausal status is a key factor that affects the utility of prognostic models for differential diagno sis of ovarian tumors. Diagnostic models of ovarian tumors are reasonable tools for predicting tumor malignancy

Range of Resection in Endometrial Cancer-Clinical Issues of Made-to-Measure Surgery.

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

Human Papillomavirus Infections and the Role Played by Cervical and Cervico-Vaginal Microbiota-Evidence from Next-Generation Sequencing Studies.

This comprehensive review encompasses studies examining changes in the cervical and cervico-vaginal microbiota (CM and CVM) in relation to human papillomavirus (HPV) using next-generation sequencing (NGS) technology. HPV infection remains a prominent global health concern, with a spectrum of manifestations, from benign lesions to life-threatening cervical cancers. The CM and CVM, a unique collection of microorganisms inhabiting the cervix/vagina, has emerged as a critical player in cervical health. Recent research has indicated that disruptions in the CM and CVM, characterized by a decrease in Lactobacillus and the overgrowth of other bacteria, might increase the risk of HPV persistence and the progression of cervical abnormalities. This alteration in the CM or CVM has been linked to a higher likelihood of HPV infection and cervical dysplasia. NGS technology has revolutionized the study of the cervical microbiome, providing insights into microbial diversity, dynamics, and taxonomic classifications. Bacterial 16S rRNA gene sequencing, has proven invaluable in characterizing the cervical microbiome, shedding light on its role in HPV infections and paving the way for more tailored strategies to combat cervical diseases. NGS-based studies offer personalized insights into an individual's cervical microbiome. This knowledge holds promise for the development of novel diagnostic tools, targeted therapies, and preventive interventions for cervix-related conditions, including cervical cancer.

Role of osteopontin in differential diagnosis of ovarian tumors.

AIM: The aim of this study was to evaluate the role of the serum osteopontin (OPN) level as a biomarker for discriminating between malignant and benign ovarian tumors. Furthermore, comparisons with the diagnostic usefulness of the other tests were performed. METHODS: The study included 114 consecutive women with ovarian tumors (82 benign and 32 malignant) who were referred to our division. RESULTS: A cut-off level of 28.0 ng/mL for OPN showed a sensitivity of 71.87% and a specificity of 89.02%. The area under the receiver-operator curve (ROC) was 0.812. There were no differences in diagnostic utility between OPN and the other studied tests. OPN levels were lower in patients with endometriotic ovarian cysts than in those with other benign ovarian tumors (14.00 vs 19.50 ng/mL; P = 0.018). The difference between the median OPN level in patients with endometriotic cysts (14.0 ng/mL) and those with malignant tumors (40.85 ng/mL) was also statistically significant (P < 0.0001). The calculated OPN/CA-125 ratio was significantly different between patients with endometriotic cysts (median, 0.36; range, 0.05-2.89) and those with other benign tumors (median, 1.25; range, 0.05-5.70) (P = 0.0002). There was also a statistically significant difference in the median OPN/CA-125 ratio between patients with endometrial cysts (median, 0.36; range, 0.05-2.89) and those with malignant tumors (median, 0.12; range, 0.01-3.39) (P = 0.004). CONCLUSION: The diagnostic utility of OPN is similar to that of ultrasonographic evaluation and CA-125 level assessment. Thus, OPN may be useful in differential diagnosis for less experienced ultrasonographers and is especially valuable for differential diagnosis of endometriotic cysts.

Usefulness of the HE4 biomarker as a second-line test in the assessment of suspicious ovarian tumors.

PURPOSE: The aim of our study was the evaluation of HE4 usefulness as a test in assessment of ovarian tumors which are suspicious and difficult to classify correctly via subjective ultrasound examination. METHODS: In this retrospective cohort study 253 women diagnosed with adnexal masses were examined preoperatively. Suspicious tumors (n = 145) were divided into groups of: "probably benign" (n = 70), "uncertain" (n = 34), and "probably malignant" (n = 41). "Uncertain" tumors were also assessed as "benign" (n = 11) or "malignant" (n = 23). The logistic regression model was performed to analyze if the serum marker improves the prediction of a malignant finding and net reclassification improvement (NRI) was calculated to measure diagnostic improvement. RESULTS: Within the analyzed group 85 (58.6%) benign and 60 (41.4%) malignant tumors were confirmed histopathologically. The comparison of HE4 with subjective ultrasound assessment showed lowered NRI in the entire analyzed group as well as in the groups of tumors classified as "probably benign" or "probably malignant" (NRI = -0.16; P = 0.0139 and NRI = -0.133; P = 0.0489, respectively). The analysis of logistic regression model confirmed that biomarkers do not improve diagnostic accuracy. The difference between areas under ROC for HE4 (0.891) and CA125 (0.902) was not statistically significant (P = 0.760). CONCLUSIONS: After subjective ultrasound assessment, the addition of the second-line test-HE4 as well as CA125 serum level does not improve diagnostic performance. However, HE4 evaluation satisfies the clinical expectations of diagnostic tools for ovarian tumors and, thus, may be useful to less experienced sonographers.

Analysis of false negative results of subjective ultrasonography assessment of adnexal masses.

OBJECTIVES: Currently transvaginal ultrasonography is the most effective method for ovarian tumor malignancy prediction. The aim of the study was to estimate the risk of false negative results in subjective interpretation of the ultrasound examination of ovarian tumors according to menopausal status. MATERIAL AND METHODS: 318 women (210 pre and 108 post menopause) with adnexal masses were diagnosed preoperatively between 2004 and 2010. Subjective assessment of tumor characteristics was conducted by experienced ultrasound examiner. Tumors were divided into groups of: "certainly benign" (n = 84), "probably benign" (n = 116), "uncertain" (n = 61), "probably malignant" (n = 47), and "certainly malignant" (n = 10). The percentage of false negative results was calculated among the first two groups according to menopausal status. RESULTS: There were 91 malignant and 227 benign adnexal masses diagnosed in histopathological evaluation. There was one false negative result of subjective interpretation of ultrasound findings in postmenopausal women - 1.6% (1/64). She was a 63-year-old woman with bilateral solid ovaries sized: 4.2 x 3.1 cm and 4.6 x 2.5 cm in ultrasound evaluation, where serous adenocarcinoma was diagnosed. There were three false negative results in premenopausal women - 2.2% (3/136). The first was a 34-year-old woman with a cyst with the appearance of ground glass of 19 x 11 cm in size where endometrioid ovarian adenocarcinoma was diagnosed. The second woman was a 32-year-old with a bilocular cyst 8 x 4.5 cm diagnosed with borderline mucinous tumor. The third patient was a 21-year-old woman with unilocular-solid cyst 4.2 x 3.2 cm where histopathological examination revealed borderline serous tumor. CONCLUSIONS: Subjective ultrasound evaluation of adnexal masses has high specificity but even in the group of tumors considered benign in premenopausal as well as postmenopausal women malignancy can be found. This occurs slightly more often before menopause.

Expression of B7-H4 in endometrial cancer and its impact on patients' prognosis.

OBJECTIVES: The aim of the study was to evaluate the B7-H4 expression in endometrial cancer cells and to investigate its relationship with patient prognosis and clinicopathological features of the disease. MATERIAL AND METHODS: We performed a single-center, retrospective cohort study that included endometrial cancer patients treated between 2012 and 2019. B7-H4 expression in specimens obtained from 63 patients was examined by immunohistochemical staining. The evaluation of B7H4 immunoreactivity was assessed using Immunoreactivity Scoring (IRS) system. RESULTS: B7-H4 reactivity was observed in all, except one, endometrial cancer patients (98%). Staining intensity: no reaction in one case, weak in 16 (24%) patients, moderate in 25 (37%), and strong in 22 (35%). Twenty-nine (46%) patients showed B7-H4 immunoreactivity in more than 60% of cells, while, in 18 (29%) cases and 16 (25%) patients, the percentages were 30-60% and < 30% respectively. Median IRS was 2 (range 0-6). We found a significantly worse overall survival (OS) rate for patients with high versus low B7-H4 IRS (p = 0.03), however, in multivariate analysis, the difference in patient survival was close to the significance level (p = 0.052). B7-H4 expression was not related to histopathological type of the tumor, tumor grade, lymph node metastases, or the FIGO stage of the disease. CONCLUSIONS: Our result suggests that B7-H4 expression might be a useful prognostic factor in endometrial cancer.