Dedifferentiated and undifferentiated ovarian carcinomas (DDOC/UDOC) are rare neoplasms defined by the presence of an undifferentiated carcinoma. In this study, we detailed the clinical, pathological, immunohistochemical, and molecular features of a series of DDOC/UDOC. We collected a multi-institutional cohort of 23 DDOC/UDOC and performed immunohistochemistry for core switch/sucrose nonfermentable (SWI/SNF) complex proteins (ARID1A, ARID1B, SMARCA4, and SMARCB1), mismatch repair (MMR) proteins, and p53. Array-based genome-wide DNA methylation and copy number variation analyses were performed on a subset of cases with comparison made to a previously reported cohort of undifferentiated endometrial carcinoma (UDEC), small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), and tubo-ovarian high-grade serous carcinoma (HGSC). The age of all 23 patients with DDOC/UDOC ranged between 22 and 71 years (with an average age of 50 years), and a majority of them presented with extraovarian disease (16/23). Clinical follow-up was available for 19 patients. Except for 2 patients, the remaining 17 patients died from disease, with rapid disease progression resulting in mortality within a year in stage II-IV settings (median disease-specific survival of 3 months). Eighteen of 22 cases with interpretable immunohistochemistry results showed loss of expression of core SWI/SNF protein(s) that are expected to result in SWI/SNF complex inactivation as 10 exhibited coloss of ARID1A and ARID1B, 7 loss of SMARCA4, and 1 loss of SMARCB1. Six of 23 cases were MMR-deficient. Two of 20 cases exhibited mutation-type p53 immunoreactivity. Methylation profiles showed coclustering of DDOC/UDOC with UDEC, which collectively were distinct from SCCOHT and HGSC. However, DDOC/UDOC showed an intermediate degree of copy number variation, which was slightly greater, compared with SCCOHT but much less compared with HGSC. Overall, DDOC/UDOC, like its endometrial counterpart, is highly aggressive and is characterized by frequent inactivation of core SWI/SNF complex proteins and MMR deficiency. Its molecular profile overlaps with UDEC while being distinct from SCCOHT and HGSC.

• MeSH
• dědičné nádorové syndromy * MeSH
• DNA-helikasy genetika   metabolismus   MeSH
• dospělí MeSH
• epiteliální ovariální karcinom MeSH
• jaderné proteiny genetika   MeSH
• karcinom * patologie   MeSH
• kolorektální nádory * MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom * MeSH
• mladý dospělý MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory endometria * patologie   MeSH
• nádory mozku * MeSH
• nádory vaječníků * genetika   patologie   MeSH
• senioři MeSH
• transkripční faktory genetika   metabolismus   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Analysis of cell-free DNA methylation (cfDNAme), alone or combined with CA125, could help to detect ovarian cancers earlier and may reduce mortality. We assessed cfDNAme in regions of ZNF154, C2CD4D and WNT6 via targeted bisulfite sequencing in diagnostic and early detection (preceding diagnosis) settings. Diagnostic samples were obtained via prospective blood collection in cell-free DNA tubes in a convenience series of patients with a pelvic mass. Early detection samples were matched case-control samples derived from the UK Familial Ovarian Cancer Screening Study (UKFOCSS). In the diagnostic set (ncases = 27, ncontrols = 41), the specificity of cfDNAme was 97.6% (95% CI: 87.1%-99.9%). High-risk cancers were detected with a sensitivity of 80% (56.3%-94.3%). Combination of cfDNAme and CA125 resulted in a sensitivity of 94.4% (72.7%-99.9%) for high-risk cancers. Despite technical issues in the early detection set (ncases = 29, ncontrols = 29), the specificity of cfDNAme was 100% (88.1%-100.0%). We detected 27.3% (6.0%-61.0%) of high-risk cases with relatively lower genomic DNA (gDNA) contamination. The sensitivity rose to 33.3% (7.5%-70.1%) in samples taken <1 year before diagnosis. We detected ovarian cancer in several patients up to 1 year before diagnosis despite technical limitations associated with archival samples (UKFOCSS). Combined cfDNAme and CA125 assessment may improve ovarian cancer screening in high-risk populations, but future large-scale prospective studies will be required to validate current findings.

• MeSH
• antigen CA-125 MeSH
• časná detekce nádoru metody   MeSH
• lidé MeSH
• metylace DNA * MeSH
• nádorové biomarkery genetika   MeSH
• nádory vaječníků * diagnóza   genetika   MeSH
• prospektivní studie MeSH
• studie případů a kontrol MeSH
• transkripční faktory Krüppel-like genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The anatomic descriptions and extents of radical hysterectomy often vary across the literature and operative reports worldwide. The same nomenclature is often used to describe varying procedures, and different nomenclature is often used to describe the same procedure despite the availability of guideline and classification systems. This makes it difficult to interpret retrospective surgical reports, analyze surgical databases, understand technique descriptions, and interpret the findings of surgical studies. OBJECTIVE: In collaboration with international experts in gynecologic oncology, the purpose of this study was to establish a consensus in defining and interpreting the 2017 updated Querleu-Morrow classification of radical hysterectomies. STUDY DESIGN: The anatomic templates of type A, B, and C radical hysterectomy were documented through a set of 13 images taken at the time of cadaver dissection. An online survey related to radical hysterectomy nomenclature and definitions or descriptions of the associated procedures was circulated among international experts in radical hysterectomy. A 3-step modified Delphi method was used to establish consensus. Image legends were amended according to the experts' responses and then redistributed as part of a second round of the survey. Consensus was defined by a yes response to a question concerning a specific image. Anyone who responded no to a question was welcome to comment and provide justification. A final set of images and legends were compiled to anatomically illustrate and define or describe a lateral, ventral, and dorsal excision of the tissues surrounding the cervix. RESULTS: In total, there were 13 questions to review, and 29 experts completed the whole process. Final consensus exceeded 90% for all questions except 1 (86%). Questions with relatively lower consensus rates concerned the definitions of types A and B2 radical hysterectomy, which were the main innovations of the 2017 updated version of the 2008 Querleu-Morrow classification. Questions with the highest consensus rates concerned the definitions of types B1 and C, which are the most frequently performed radical hysterectomies. CONCLUSION: The 2017 version of the Querleu-Morrow classification proved to be a robust tool for defining and describing the extent of radical hysterectomies with a high level of consensus among international experts in gynecologic oncology. Knowledge and implementation of the exact definitions of hysterectomy radicality are imperative in clinical practice and clinical research.

• MeSH
• cervix uteri MeSH
• hysterektomie metody   MeSH
• konsensus MeSH
• lidé MeSH
• nádory ženských pohlavních orgánů * MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The substantial material and legislative investments in establishing and maintaining cytological screening in the Czech Republic represent barriers to a direct transition to primary HPV screening. Therefore, the LIBUSE project was implemented to test the efficacy of phasing in HPV DNA testing as a co-test to cytology in routine screening of women >30 years of age. METHODS: Women aged 30 to 60 years who underwent regular annual Pap smears were co-tested for HPV DNA with selective 16/18 genotyping at 3-year intervals. All HPV 16/18-positive cases and/or cases with a severe abnormality in cytology were sent for colposcopy; HPV non-16/18-positive cases and LSILs were graded using p16/Ki67 dual-stain cytology, and positive cases were sent for colposcopy. RESULTS: Overall, 2409 patients were included. After the first combined screening (year 'zero') visit, 7.4% of women were HPV-positive and 2.0% were HPV16/18-positive; only 8 women had severe Pap smear abnormalities. Triage by dual staining was positive in 21.9% of cases (28/128). Biopsy confirmed 34 high-grade precancer lesions. At the second combined visit (year 'three'), the frequency of HPV infection (5.3% vs. 7.4%) frequency of HPV16/18 (1.1% vs. 2.0%), referrals for colposcopy (35 vs. 83), and biopsy verified high-grade lesions (5 vs. 34) were significantly lower (all P ≤ 0.001). CONCLUSION: The addition of HPV DNA testing with selective genotyping of HPV16/18 to existing cytology screening significantly increased the safety of the program. The gradual introduction of HPV testing was well received by healthcare professionals and patients, and can facilitate transformation of the cytology-based screening. ClinicalTrials.gov Identifier: NCT05578833.

• MeSH
• barvení a značení MeSH
• časná detekce nádoru MeSH
• DNA MeSH
• dospělí MeSH
• dysplazie děložního hrdla * diagnóza   MeSH
• infekce papilomavirem * MeSH
• lidé MeSH
• lidský papilomavirus 16 genetika   MeSH
• lidský papilomavirus 18 genetika   MeSH
• nádory děložního čípku * MeSH
• Papanicolaouův test MeSH
• plošný screening MeSH
• třídění pacientů MeSH
• vaginální stěr MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

High-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies. Many HGSC patients have excess fluid in the peritoneum called ascites. Ascites is a tumour microenvironment (TME) containing various cells, proteins and extracellular vesicles (EVs). We isolated EVs from patients' ascites by orthogonal methods and analyzed them by mass spectrometry. We identified not only a set of 'core ascitic EV-associated proteins' but also defined their subset unique to HGSC ascites. Using single-cell RNA sequencing data, we mapped the origin of HGSC-specific EVs to different types of cells present in ascites. Surprisingly, EVs did not come predominantly from tumour cells but from non-malignant cell types such as macrophages and fibroblasts. Flow cytometry of ascitic cells in combination with analysis of EV protein composition in matched samples showed that analysis of cell type-specific EV markers in HGSC has more substantial prognostic potential than analysis of ascitic cells. To conclude, we provide evidence that proteomic analysis of EVs can define the cellular composition of HGSC TME. This finding opens numerous avenues both for a better understanding of EV's role in tumour promotion/prevention and for improved HGSC diagnostics.

• MeSH
• ascites metabolismus   patologie   MeSH
• extracelulární vezikuly * metabolismus   MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• nádory vaječníků * diagnóza   MeSH
• proteomika MeSH
• serózní cystadenokarcinom * diagnóza   genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Persistent infection with high-risk types of human papillomaviruses (HPV) is a major cause of cervical cancer, and an important factor in other malignancies, for example, head and neck cancer. Despite recent progress in screening and vaccination, the incidence and mortality are still relatively high, especially in low-income countries. The mortality and financial burden associated with the treatment could be decreased if a simple, rapid, and inexpensive technology for HPV testing becomes available, targeting individuals for further monitoring with increased risk of developing cancer. Commercial HPV tests available in the market are often relatively expensive, time-consuming, and require sophisticated instrumentation, which limits their more widespread utilization. To address these challenges, novel technologies are being implemented also for HPV diagnostics that include for example, isothermal amplification techniques, lateral flow assays, CRISPR-Cas-based systems, as well as microfluidics, paperfluidics and lab-on-a-chip devices, ideal for point-of-care testing in decentralized settings. In this review, we first evaluate current commercial HPV tests, followed by a description of advanced technologies, explanation of their principles, critical evaluation of their strengths and weaknesses, and suggestions for their possible implementation into medical diagnostics.

• MeSH
• infekce papilomavirem * komplikace   MeSH
• lidé MeSH
• lidské papilomaviry MeSH
• nádory děložního čípku * MeSH
• Papillomaviridae genetika   MeSH
• technologie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

An international joint statement about the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer was published in 2016, warning about the uncritical use of HIPEC outside controlled studies. This statement has now been updated after the most recent literature was reviewed by the participating study groups and societies. HIPEC became a treatment option in patients with advanced colon cancer after positive results of a randomized trial comparing surgery and HIPEC versus palliative treatment alone. Although this trial did not compare the added value of HIPEC to surgery alone, HIPEC for the treatment of peritoneal metastases was in the subsequent years generalized to many other cancer types associated with peritoneal carcinomatosis including epithelial ovarian cancer (EOC). In the meantime, new evidence from prospective randomized trials specifically for EOC-patients emerged, with however contradicting results and several quality aspects that made the interpretation of their findings critical. Moreover, three additional trials in colorectal cancer failed to confirm the previously presumed survival benefit through the implementation of HIPEC in peritoneally disseminated colorectal cancers. Based on a still unclear and inconsistent landscape, the authors conclude that HIPEC should remain within the remit of clinical trials for EOC-patients. Available evidence is not yet sufficient to justify its broad endorsement into the routine clinical practice.

• MeSH
• epiteliální ovariální karcinom patologie   MeSH
• hypertermická intraperitoneální peroperační chemoterapie MeSH
• indukovaná hypertermie * metody   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• nádory vaječníků * farmakoterapie   patologie   MeSH
• prospektivní studie MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Rakousko MeSH
• Švýcarsko MeSH

Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8+ effector T (TEFF) cells and TIM3+PD1+, hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8+ T cells. Conversely, CD8+ T cells from immunologically hot tumors like non-small cell lung carcinoma (NSCLC) are enriched in ICI-responsive TCF1+ PD1+ T cells. Spatial B-cell profiling identifies patterns of in situ maturation and differentiation associated with mTLSs. Moreover, B-cell depletion promotes signs of a dysfunctional CD8+ T cell compartment among tumor-infiltrating lymphocytes from freshly isolated HGSOC and NSCLC biopsies. Taken together, our data demonstrate that - at odds with NSCLC - HGSOC is associated with a low density of follicular helper T cells and thus develops a limited number of mTLS that might be insufficient to preserve a ICI-sensitive TCF1+PD1+ CD8+ T cell phenotype. These findings point to key quantitative and qualitative differences between mTLSs in ICI-responsive vs ICI-irresponsive neoplasms that may guide the development of alternative immunotherapies for patients with HGSOC.

• MeSH
• CD8-pozitivní T-lymfocyty MeSH
• ektopické lymfoidní struktury * MeSH
• fenotyp MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• nádory plic * MeSH
• nádory vaječníků * patologie   MeSH
• nemalobuněčný karcinom plic * MeSH
• tumor infiltrující lymfocyty MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Publikace se zaměřuje na onkologická gynekologická onemocnění. Určeno odborné veřejnosti.

• Klíčová slova
• onkogynekologie,
• MeSH
• lékařská onkologie MeSH
• nádory ženských pohlavních orgánů MeSH

• Konspekt
• Gynekologie. Porodnictví
• NLK Obory
• gynekologie a porodnictví
• onkologie
• NLK Publikační typ
• kolektivní monografie

In recent years the role of diagnostic imaging by pelvic ultrasound in the diagnosis and staging of gynecological cancers has been growing exponentially. Evidence from recent prospective multicenter studies has demonstrated high accuracy for pre-operative locoregional ultrasound staging in gynecological cancers. Therefore, in many leading gynecologic oncology units, ultrasound is implemented next to pelvic MRI as the first-line imaging modality for gynecological cancer. The work herein is a consensus statement on the role of pre-operative imaging by ultrasound and other imaging modalities in gynecological cancer, following European Society guidelines.

• MeSH
• gynekologie * MeSH
• konsensus MeSH
• lidé MeSH
• nádory ženských pohlavních orgánů * diagnostické zobrazování   MeSH
• pánev MeSH
• ultrasonografie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH