Mateusz Kozłowski

Association of Tissue Expression of LAG-3 and TIM-3 with Clinical Features in Ovarian Cancer

One of the most prevalent types of cancer among women is ovarian cancer. The search for ovarian cancer markers is constantly ongoing. Evaluation of LAG-3 and TIM-3 protein expression in ovarian cancer tissue and its role in distinguishing the clinical signs stated were the objectives of this study. Methods: A total of 58 ovarian cancer patients were recruited for this study. The cohort was split into two groups: one for high-grade serous ovarian cancer (HGSOC) and another for ovarian cancer that was not HGSOC (non-HGSOC). LAG-3 and TIM-3 protein expression in ovarian cancer tissue samples was evaluated by immunohistochemistry. StatView 5.0 software (Carry, NC, USA) was used for all statistical analyses. Both LAG-3 and TIM-3 proteins mostly showed positive, moderately positive, or strongly positive expression. This study shows that LAG-3 could be a marker associated with BMI in the non-HGSOC group. TIM-3 may be a marker associated with age in a group of all ovarian cancers. LAG-3 expression is associated with TIM-3 expression in the total cohort and the HGSOC and non-HGSOC groups.

The Role of microRNA in the Prognosis and Diagnosis of Ovarian Cancer

Ovarian cancer (OC) is one of the most common cancers in women. Biomarkers for OC are still being sought. The aim of this review was to evaluate microRNAs in the prognosis and diagnosis of OC. We conducted a literature review searching for articles published from January 2014 to September 2024. We included articles presenting the association of microRNAs with ovarian cancer prognosis, where patient survival was shown by the Kaplan–Meier curve, and articles presenting the association of microRNAs with ovarian cancer diagnosis, where the results were presented as an ROC curve. MicroRNAs are promising clinical markers in ovarian cancer patients. As is shown here, expression (high or low) of various miRNAs was differentially associated with survival in OC patients, with some miRNAs being associated with a longer survival and some with a shorter survival. In the absence of diagnostic markers for OC, the raised role of miRNAs in diagnosis seems all the more important. The diagnostic value of miRNAs has been shown, mostly as blood biomarkers, although they have also been evaluated as tissue or urine markers. MiRNAs have an important role as clinical biomarkers for ovarian cancer, not only as single molecules, but also as biomarker pairs or panels of miRNAs. It should be noted that most of the miRNAs reviewed here have been studied once, so despite the promising results, it seems necessary to conduct studies to confirm or negate the results obtained.

The Role of Long Non-Coding RNAs in Ovarian Cancer Cells

Among the most deadly malignancies that strike women worldwide, ovarian cancer is still one of the most common. The primary factor affecting a patient’s survival is early lesion discovery. Unfortunately, because ovarian cancer is a sneaky illness that usually manifests as nonspecific symptoms only in advanced stages, its early detection and screening are challenging. A lot of research is being conducted on effective methods of diagnosing and treating ovarian cancer. Recently, non-coding RNAs (ncRNAs) have gained great popularity, which are considered to be the main regulators of many cellular processes, especially those occurring in cancer. LncRNAs are also being studied for their therapeutic use in the treatment of ovarian cancer and their use in diagnostics and as indicators of poor prognosis. In this article, we reviewed lncRNAs described in the literature that may play an important role in ovarian cancer.

Vitamins in Gynecologic Malignancies

The combination of vitamin A and D derivatives with classical chemotherapeutic treatments results in more satisfactory outcomes. The use of drug combinations, such as 9cUAB130 with carboplatin and cisplatin with TAC-101, shows enhanced cytotoxic effects and reductions in ovarian tumor volume compared to single-drug treatments. Combining cisplatin with calcitriol and progesterone increases VDR expression, potentially enhancing the effectiveness of anticancer therapy in ovarian cancer. The effectiveness of vitamin derivatives in anticancer treatment may vary depending on the characteristics of the tumor and the cell line from which it originated. An increase in thiamine intake of one unit is associated with an 18% decrease in HPV infection. Higher intake of vitamin C by 50 mg/day is linked to a lower risk of cervical neoplasia. Beta-carotene, vitamin C, and vitamin E are associated with risk reductions of 12%, 15%, and 9% in endometrial cancer, respectively. A balanced daily intake of vitamins is important, as both deficiency and excess can influence cancer development. It has been observed that there is a U-shaped relationship between group B vitamins and metabolic markers and clinical outcomes.

Forensic DNA Recovery from FFPE Tissue Using the Maxwell® RSC Xcelerate Kit: Optimization, Challenges, and Limitations

Background/Objectives: Obtaining reliable DNA profiles from archival tissue preserved as formalin-fixed, paraffin-embedded (FFPE) samples remains a major challenge in both forensic and medical evaluations. The quality of DNA isolated from FFPE material is frequently compromised due to formalin-induced fragmentation and chemical modifications. These limitations are particularly relevant in cases of suspected medical malpractice related to cancer diagnosis or treatment, where retrospective molecular analyses may provide critical evidence. The aim of this study was to evaluate the performance of the Maxwell® RSC Xcelerate DNA FFPE Kit (Promega) in generating DNA profiles from archival FFPE tissue blocks of endometrial cancer and to identify the limitations associated with this approach. Methods: Archival FFPE blocks of endometrial cancer were analyzed using the Maxwell® RSC Xcelerate DNA FFPE Kit. DNA yield, purity, and degradation indices were assessed using standard real-time PCR-based quantification methods. Short tandem repeat (STR) profiling was performed with forensic genotyping kits, and the completeness, allele balance, and reliability of obtained profiles were evaluated. The obtained results were compared with reference quality thresholds commonly used in forensic practice. Results: The Maxwell® RSC Xcelerate Kit allowed for recovery of relatively high DNA yields with consistently low degradation indices, confirming good extraction efficiency from FFPE samples. Nevertheless, despite favorable quantitative values, the generation of complete STR profiles was often unsuccessful. Partial or incomplete profiles were frequent, characterized by allele dropout and imbalance, which substantially reduced their evidentiary value. These findings suggest that DNA fragmentation and fixation-related artifacts impair amplification efficiency and limit the usefulness of STR analysis. Conclusions: This study emphasizes the persistent challenges of DNA profiling from FFPE tissue in forensic-medical contexts. Although the Maxwell® RSC Xcelerate Kit demonstrated effective DNA recovery, the ability to generate complete and interpretable STR profiles remained limited. Further refinement of extraction protocols, as well as improved interpretative strategies, are required to enhance the reliability and evidentiary significance of molecular analyses based on archival FFPE material.

IL-4, IL-7, IL-9, NT, NRP1 May Be Useful Markers in the Diagnosis of Endometrial Cancer

The search for novel endometrial cancer diagnostic biomarkers is pertinent. The purpose of this study was to determine if IL-4, IL-7, IL-9, IL-10, NT, TSP-2, and NRP1 could be used as novel, helpful markers for the detection of endometrial cancer. Ninety-three women diagnosed with endometrial cancer (EC) and sixty-six patients with noncancerous endometrial lesions (NCEL) were included in this study. ELISA was used to measure the concentrations of the proteins tested. Median serum levels of IL-4, IL-7, IL-9, NT, and NRP1 were significantly higher in the EC group compared with NCEL. The cut-off level of IL-4 was set at 802.26 pg/mL with a sensitivity of 83.87% and a specificity of 50% (AUC = 0.7, p = 0.000023). The cut-off level of IL-7 was set at 133.63 ng/L with a sensitivity of 96.77% and a specificity of 75.76% (AUC = 0.91, p < 0.000001). The cut-off level of IL-9 was set at 228.79 pg/mL with a sensitivity of 69.89% and a specificity of 81.82% (AUC = 0.8, p < 0.000001). The cut-off level of NT was set at 275.43 pmol/L with a sensitivity of 94.62% and a specificity of 59.09% (AUC = 0.83, p < 0.000001). The cut-off level of NRP1 was set at 30.37 ng/mL with a sensitivity of 81.72% and a specificity of 57.58% (AUC = 0.71, p = 0.000004). This study suggests the clinical utility of IL-4, IL-7, IL-9, NT, and NRP1 in the diagnosis of endometrial cancer. Nevertheless, these biomarkers may also have prognostic or predictive value, which should be tested in future studies.

Could Vaspin Be a Potential Diagnostic Marker in Endometrial Cancer?

Obesity and being overweight are risk factors for many types of cancer, including endometrial cancer. Adipose tissue is thought to be an endocrine organ that produces various hormones, including one known as vaspin. Insulin resistance, metabolic syndrome and type 2 diabetes are all associated with higher vaspin levels. A total of 127 patients divided into study (endometrial cancer) and control groups (non-cancerous) participated in this research. Serum vaspin levels were measured for all patients. The analysis was performed while taking into account grading and staging. In order to assess the usefulness of the tested protein as a new diagnostic marker, we used the plotting of a curve (ROC) and the calculation of the AUC curve to characterize the sensitivity and specificity of the parameters tested. We concluded that there were significantly lower vaspin levels in patients with endometrial cancer compared to patients with benign endometrial lesions. Vaspin may be a useful diagnostic marker in separating benign lesions from endometrial cancer.

Evaluation of Tissue Expression of Vaspin and Serum Vaspin Concentration as a Prognostic and Risk Factor in Endometrial Cancer

Adipose tissue is a multifunctional endocrine organ. One of the biologically active substances is vaspin, which is part of the serpin family. The purpose of the following study is to determine the possibility of using vaspin as a prognostic and risk factor in endometrial cancer. The study included 127 patients with abnormal uterine bleeding. To determine the value of adipokine, the study used Kaplan-Meier curves to estimate patients survival. Univariate and multivariate analyses were performed simultaneously using the Cox regression model. Tissue expression of vaspin was assessed in patients from the study group (endometrial cancer) and the control group (non-cancerous). We found that higher levels of vaspin are found in obese people, with lower staging (FIGO I and II), lower grading (G1), no LVSI metastases and no lymph node metastases. Higher serum vaspin levels are an independent protective factor for endometrial cancer. We concluded that endometrial cancer patients with serum vaspin concentrations above the median have longer DFS compared to patients with concentrations below the median. Considering multivariate analysis, vaspin concentrations above the median are independent favourable prognostic factors for endometrial cancer. Tissue expression of vaspin cannot be a histological marker to distinguish between cancer and non-cancerous lesions and between different grading levels.

Late Diagnosis of Swyer Syndrome in a Patient with Bilateral Germ Cell Tumor Treated with a Contraceptive Due to Primary Amenorrhea

Swyer syndrome is a special form of DSD (disorders of sex development), so-called pure gonadal dysgenesis with a karyotype 46, XY and a female phenotype. One of the most important problems in patients with DSD is the risk of gonadal tumors. We present a case of a 26-year-old patient with Swyer syndrome. The patient had primary amenorrhea and no puberty characteristics. In ultrasound imaging in the vicinity of the uterus, there were two homogeneous structures. A genetic diagnosis was also performed, which showed karyotype 46, XY. The patient underwent a bilateral gonadectomy. Histopathological examination revealed the presence of dysgerminoma in both dysgenetic gonads. The follow-up of five years now did not show any changes suspected of invasion. We concluded that the primary amenorrhea, along with the absence of development of sexual characteristics, should prompt an expanded diagnosis for disorders of sex development. Gonadal dysgerminoma should be suspected even in the absence of tumor features on ultrasound and blood laboratory tests. Early prophylactic gonadectomy could protect patients from developing tumors in dysgenetic gonads.

The Role of Selenium and Manganese in the Formation, Diagnosis and Treatment of Cervical, Endometrial and Ovarian Cancer

Selenium (Se) and manganese (Mn) are essential micronutrients that are important elements of cell metabolism. They are involved in the composition of enzyme systems and regulate enzyme activity. Disturbances in the homeostasis of these micronutrients affect the development of many diseases and carcinogenesis, which can be linked to increased levels of oxidative stress and impaired antioxidant properties of many enzymes. Selenium has a very important function in maintaining immune-endocrine, metabolic and cellular homeostasis. Manganese, on the other hand, is important in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activity. We review the role of selenium and manganese and their effects on tumor growth, metastasis potential and remodeling of the microenvironment. We also describe their role as potential biomarkers in the diagnosis and the potential for the use of Se- and Mn-containing compounds in composition for the treatment of cancer of the reproductive organs.

Therapeutic Management of Rare Primary Ovarian Neoplasms: Carcinosarcoma, Leiomyosarcoma, Melanoma and Carcinoid

Carcinosarcoma, leiomyosarcoma, melanoma and carcinoid as primary tumors in the ovary are extremely rare. In this paper, the authors reviewed the literature from 2010 to 2021, based on specific criteria, to analyze the treatment of these rare ovarian neoplasms. We also aimed to verify whether modern therapies have been found in recent years. For this article, 80 papers were finally selected. The vast majority of the articles were clinical case reports. Despite single mentions of new potential pharmacological treatments, surgery (radical or fertility-sparing) is definitely the mainstay of treatment. There are currently no treatment guidelines for these tumors. A review of the literature has revealed the use of various adjuvant treatments. We, therefore, believe that a more detailed understanding of the biology of these tumors is necessary in order to find new target points for treatment. We would like to emphasize the importance of creating an international database of rare ovarian tumors which would make it possible to gather data from various oncological centers and enable further research into these neoplasms.

Long-Term Follow-Up of a Female Patient Treated with Olaparib—Hope for a Long Life without Relapse?

Ovarian cancer is one of the most common cancers of the reproductive organs. As there are no symptoms in the early stages, it is mainly detected in the advanced stages. Even then, the symptoms are non-specific and include, for example, abdominal pain, early satiety, or changes in bowel habits. Both biochemical marker levels and imaging studies are used in the initial diagnosis. However, it should be emphasized that they are not characterized by high specificity. Treatment is multistage, and usually first-line debulking surgery is used followed by platinum-based chemotherapy. Here we present a clinical case of a 56-year-old female, a carrier of a mutation in the BRCA1 gene, with a history of breast cancer and with recurrent epithelial ovarian cancer. The patient was qualified for treatment with a PARP inhibitor and is currently undergoing treatment with olaparib. In the patient’s follow up of 50 months to date, there has been no recurrence of cancer. Few side effects have been observed, and the most serious one that can be effectively treated is anemia. On the basis of the described case, the authors concluded that olaparib treatment is effective, relatively safe, and does not significantly affect daily functioning.

An Unusual Case of Vulvar Involvement in the Course of Granulomatosis with Polyangiitis

Granulomatosis with polyangiitis is a rare autoimmune disease with the presence of c-ANCA in most cases. It involves necrotizing inflammation in small and medium-sized vessels with multiple granulomas. The disease can affect many systems, but the typical triad of attacked systems are the upper and lower respiratory tracts and kidneys, with varying degrees of severity. Involvement of the respiratory tract may manifest, among other symptoms, as nasal crusting, nosebleeds, and dyspnea. Among patients with granulomatosis with polyangiitis, only less than 1% develop genitourinary system involvement. We present a case study of a 36-year-old woman with an 8-year-long GPA history and a lesion, which, due to its appearance and accompanying symptoms, aroused the suspicion of a neoplasm but was proven to be a granuloma with a nontypical location. The systemic disease was treated with glucocorticosteroids and cyclophosphamide. The lesion on the labium minus was surgically removed. We concluded that the macroscopic picture of GPA of the vulva and vulvar cancer is similar. The patient’s medical history may help differentiate GPA and vulvar cancer. Although vulvar GPA is extremely rare, it should be considered in the differential diagnosis of vulvar lesions, especially those suspected to be oncological.