Uterine sarcomas with KAT6B/A::KANSL1 fusion represent a new entity characterized by bland morphology, commonly with hybrid features of low-grade endometrial stromal sarcoma (LG-ESS) and tumors with smooth muscle differentiation. In our study, we performed a detailed morphological, immunohistochemical, and molecular analysis of 9 cases of these tumors. Six of those had been originally diagnosed as LG-ESS, one as leiomyoma, one as leiomyosarcoma, and the remaining case as sarcoma with the KAT6B/A::KANSL1 fusion. Seven cases showed overlapping features between endometrial stromal and smooth muscle tumors, one case resembled cellular leiomyoma, and one case resembled high-grade endometrial stromal sarcoma. Immunohistochemically, the tumors showed a common expression of smooth muscle markers and endometrial stromal markers. Molecular findings showed the KAT6B/A::KANSL1 fusion in all cases (by NGS and FISH). In addition, mutations affecting genes such as TP53, PDGFRB, NF1, RB1, PTEN, ATM, RB1, FANCD2, and TSC1 were present in all 5 cases with aggressive behavior. One patient with no evidence of disease showed no additional mutations, while another harbored a mutation of a single gene (ERCC3). Of the 8 patients with available follow-up, two died of disease, 3 are currently alive with disease, and 3 have no evidence of disease. The correct recognition of tumors with the KAT6B/A::KANSL1 fusion is essential because despite the bland morphological features of most cases, these tumors have a propensity for aggressive behavior.

• MeSH
• dospělí MeSH
• endometriální stromální sarkom genetika   patologie   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• histonacetyltransferasy genetika   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádory dělohy * patologie   genetika   MeSH
• sarkom genetika   patologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Mismatch repair-deficient (dMMR) endometrial cancer (EC) is an inflamed phenotype with poor outcomes when meeting high-risk criteria and limited treatment options in the adjuvant setting. We report protocol-prespecified subgroup analysis of patients with dMMR tumors from the phase III ENGOT-en11/GOG-3053/KEYNOTE-B21 study (ClinicalTrials.gov identifier: NCT04634877) in newly diagnosed, high-risk EC after surgery with curative intent. Patients were randomly assigned to pembrolizumab 200 mg or placebo (six cycles) plus carboplatin-paclitaxel (four to six cycles) once every 3 weeks, then pembrolizumab 400 mg or placebo once every 6 weeks (six cycles), respectively. MMR status was a stratification factor. Patients received radiotherapy at investigator discretion. Investigator-assessed disease-free survival (DFS) was a primary end point. No formal hypothesis testing was performed for subgroup analysis. In the intention-to-treat population, 141 patients in the pembrolizumab arm and 140 in the placebo arm had dMMR tumors. At this interim analysis, hazard ratio for DFS favored pembrolizumab (0.31 [95% CI, 0.14 to 0.69]); median DFS was not reached in either group. Two-year DFS rates were 92.4% (95% CI, 84.4 to 96.4) and 80.2% (95% CI, 70.8 to 86.9), respectively. No new safety signals occurred. Longer-term follow-up of outcomes will be evaluated at final analysis. Preplanned subgroup analysis on the basis of the study's stratification factors suggests that pembrolizumab plus chemotherapy improves DFS and is clinically relevant for patients with dMMR tumors in the curative-intent setting.

• MeSH
• adjuvantní chemoterapie MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• karboplatina aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory endometria * patologie   farmakoterapie   mortalita   terapie   MeSH
• oprava chybného párování bází DNA * MeSH
• paclitaxel * aplikace a dávkování   MeSH
• přežití bez známek nemoci MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Endometrial carcinomas (EC) of no special molecular profile (NSMP) represent the largest molecular category of EC, comprising a mixture of tumors with different histology and molecular profiles. These facts likely point to different tumor biology, clinical outcomes, and targeted therapy responses within this molecular category. The PIK3CA is currently the only targetable kinase oncoprotein directly implicated in EC carcinogenesis. Investigating a unique single-institution cohort, we attempted to stratify NSMP ECs based on the presence of the PIK3CA pathogenic mutation. Those cases were further analyzed for other well-established-associated oncogenic driver gene mutations. Histological and clinical variables were also correlated in each case. Altogether, 175 ECs were prospectively tested by a limited custom NGS panel containing ARID1A, BCOR, BRCA1, BRCA2, CTNNB1, KRAS, MLH1, MSH2, MSH6, NRAS, PIK3CA, PMS2, POLD1, POLE, PTEN,and TP53 genes. We identified 24 PIK3CA mutated cases in the group of 80 NSMP ECs, with another co-occurring mutation in at least one oncogenic driver gene (CTNNB1, PTEN, ARID1A, KRAS, BCOR, PMS2) in 19 cases. In conclusion, a limited NGS panel can effectively test EC tissue for specific pathogenetically relevant oncogene mutations. The NSMP EC category contains 30% of the PIK3CA mutated cases. Of those, 21% contain the PIK3CA mutation as a sole EC-associated oncogene mutation, while 79% harbor at least one more mutated gene. These findings may inform future healthcare planning and improve the effectiveness of EC patient selection for the PIK3CA-targeted therapy.

• MeSH
• cílená molekulární terapie MeSH
• dospělí MeSH
• fosfatidylinositol-3-kinasy třídy I * genetika   antagonisté a inhibitory   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• nádorové biomarkery * genetika   MeSH
• nádory endometria * genetika   patologie   farmakoterapie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výběr pacientů MeSH
• vysoce účinné nukleotidové sekvenování * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Endometrial stromal tumors are rare lesions with a diverse morphology, which may make achieving the correct diagnosis challenging in some cases. We report a case of a uterine mesenchymal tumor diagnosed as endometrial stromal nodule with a peculiar whorled morphology and GREB1::CTNNB1 fusion confirmed by transcriptome RNA sequencing. The tumor was sharply demarcated, lacked invasive growth, and had benign behavior, as the patient remained without disease recurrence 15 years later. Immunohistochemically, the tumor cells showed diffuse nuclear expression of beta-catenin, confirming the activation of the beta-catenin pathway. Our case represents only the 4th reported case of CTNNB1-rearranged endometrial stromal tumor with extensive whorling. The biological nature of uterine tumors characterized by whorled morphology and rearrangement of CTNNB1 is not yet clear, which underscores the importance of genetic profiling for accurate diagnosis and potential targeted therapies in malignant cases.

• MeSH
• beta-katenin * genetika   MeSH
• endometriální stromální nádory * patologie   genetika   diagnóza   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• genová přestavba MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery genetika   analýza   MeSH
• nádorové proteiny MeSH
• nádory endometria * genetika   patologie   diagnóza   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Prevalence detekce izolovaných nádorových buněk a mikrometastáz v sentinelové uzlině stoupá díky jejich podrobnému zpracování formou ultrastagingu. Předkládaná práce poskytuje aktuální přehled literatury od ledna roku 2019 do září roku 2024 se zaměřením na nízkoobjemové postižení regionálních uzlin, jeho prevalenci, prognózu a souvislost s molekulární klasifikací. Přítomnost mikrometastáz je aktuálně považována za metastatické postižení lymfatických uzlin, avšak s lepší prognózou než makrometastázy, dle toho je volen i terapeutický postup společný pro obě tyto kategorie uzlinového postižení. Naopak přítomnost izolovaných nádorových buněk není v rámci Mezinárodní federace gynekologie a porodnictví (FIGO) 2023 stagingu považována za uzlinové postižení a neovlivňuje doporučený terapeutický postup, protože doposud nebyly prokázány signifikantní prognostické důsledky jejich přítomnosti.

Due to the implementation of sentinel lymph node ultrastaging, the prevalence of isolated tumor cells and micrometastases have increased. This literature review comprises of articles published between January 2019 and September 2024 aiming at low-volume metastases in regional lymph nodes, their prognosis, and links to molecular classification. Micrometastases are currently considered as having metastatic lymph node involvement; however, they have a better prognosis than macrometastases. Accordingly, therapy is tailored. In contrast, isolated tumor cell presence is not considered metastatic involvement according to International Federation of Gynecology and Obstetrics (FIGO) 2023 staging and does not affect the therapeutic procedure because their significant prognostic importance has not been proven so far.

• Klíčová slova
• nízkoobjemové postižení uzlin,
• MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• metastázy nádorů diagnóza   patologie   MeSH
• mikrometastázy MeSH
• nádory endometria * diagnóza   epidemiologie   komplikace   MeSH
• prognóza MeSH
• sentinelová uzlina * patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

• Klíčová slova
• osimertinib, durvalumab,
• MeSH
• ftalaziny terapeutické užití   MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   terapeutické užití   MeSH
• nádory endometria farmakoterapie   MeSH
• nádory vaječníků * farmakoterapie   MeSH
• PARP inhibitory terapeutické užití   MeSH
• piperaziny terapeutické užití   MeSH
• protinádorové látky imunologicky aktivní aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• protinádorové látky aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie MeSH
• Check Tag
• lidé MeSH

BACKGROUND: This study aimed to evaluate the effectiveness of different tracers ́ application techniques for sentinel lymph node (SLN) detection in women with endometrial cancer undergoing laparotomy. Additionally, potential risk factors for SLN detection failure were assessed. METHODS: We retrospectively analyzed data from 248 endometrial cancer patients who underwent abdominal surgery with SLN mapping between January 2020 and March 2024. Statistical analyses were conducted using the Wilcoxon rank sum test for continuous variables and either Pearson's chi-square test or Fisher's exact test for categorical variables, with a significance level set at p < 0.05. RESULTS: Group I + S consisted of 147 women with intracervical and subserosal tracers ́application and group I + I included 101 women with intracervical and intrafundal application. Successful detection of SLN on both sides was achieved in 39.9% (99/248) of all patients, in 38.1% (56/147) in the I + S group and in 42.6% (43/101) in the I + I group, respectively. SLNs were identified in 32.7% (81/248) of all patients on only one side of the pelvis, in 31.3% (46/147) in the I + S and in 34.7% (35/101) in the I + I group, respectively. No SLNs were detected in 27.4% (68/248) of all subjects, comprising 30.6% (45/147) from the I + S and 22.8% (23/101) from the I + I group. Although the success rate of SLN detection was higher in the I + I group and on the right side of the pelvis regardless of the detection method, these differences were not statistically significant. An age exceeding 66.3 years was recognized as a critical risk factor for successful detection, other followed factors did not demonstrate a statistically significant impact on overall detection success. Additional significant risk factors were identified: depth of tumor myometrial invasion on the right side, history of pelvic surgery, and total tumor volume on the left side. CONCLUSIONS: The study did not reveal significant differences in SLN mapping success between the groups receiving intracervical + intrafundal and intracervical + subserosal tracers ́applications among endometrial cancer patients treated via open surgery. Overall, older age emerged as the most critical risk factor for SLN detection failure, while other assessed factors did not show a statistically significant impact on overall detection success. TRIAL REGISTRATION: Institution University Hospital Královské Vinohrady, Prague, Czech Republic. REGISTRATION NUMBER: EK-VP-21-0-2023. Date of registration 7-JUN-2023. This study was retrospectively registered in compliance with the Declaration of Helsinki.

• MeSH
• biopsie sentinelové lymfatické uzliny * metody   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• nádory endometria * chirurgie   patologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sentinelová uzlina * patologie   diagnostické zobrazování   chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

Terapie lokálně pokročilých, rekurentních či metastazujících nádorů těla dělohy zaznamenala v posledních letech s příchodem imunoterapie zásadní posun. Potencionálně kurativní chirurgický výkon, eventuálně radioterapie zůstávají samozřejmě možností volby, jsou-li proveditelné. Preferovaným standardem systémové léčby je v současnosti jednoznačně indikace imunoterapie s chemoterapií karboplatinou a paklitaxelem, a to jednoznačně již v první linii paliativní léčby. V tuto chvíli získaly registraci v České republice v první linii dostarlimab, pembrolizumab a durvalumab. U pacientek, které byly již v první linii předléčeny chemoterapií, se nabízí jako možnost volby kombinace pembrolizumabu s lenvatinibem nebo monoterapie dostarlimabem nebo pembrolizumabem u pacientek s nádory s defektem v mismatch repair genech / vysokou mikrosatelitovou instabilitou. Samozřejmě hormonální léčba nebo samostatná chemoterapie stále zůstávají jako možnost volby u pacientek, které nejsou kandidátky imunoterapie.

The treatment of the locally advanced, recurrent or metastatic endometrial cancer experienced in the recent years significant progress with the introducing of the immunotherapy into daily practice. Potentially curative surgical procedure, eventually radiotherapy remains of course the treatment of choice if feasible. The gold standard in the systemic treatment is without any doubt the combination of chemotherapy of carboplatin with paclitaxel and the indication of the immunotherapy should be already in the first line. At this moment there are three molecules with registration in Czech Republic in this indication - dostarlimab, pembrolizumab and durvalumab. In the case of patients previously treated with chemotherapy there is the possibility of combination of pembrolizumab with lenvatinib or monotherapy with dostarlimab or pembrolizumab in the case of deficient mismatch repair / microsatellite instability-high tumors. Of course, hormonal treatment or chemotherapy remains the treatment of choice in the patients where immunotherapy is not feasible.

• Klíčová slova
• studie GARNET, dostarlimab,
• MeSH
• humanizované monoklonální protilátky farmakologie   terapeutické užití   MeSH
• imunoterapie metody   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory dělohy * farmakoterapie   MeSH
• nežádoucí účinky léčiv MeSH
• přehledy MeSH
• protokoly protinádorové léčby MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

Minimally invasive surgery is the method of choice in endometrial cancer. Experience in procedures assisted by a robotic system is growing rapidly. One of the new bipolar ones is a Vessel Sealer, with sealing and cutting function. The aim of the study was to compare robotic surgery assisted with the da Vinci X system with use of the Vessel Sealer or without it. The study included 25 patients with high-risk endometrial cancer after completed pelvic and paraaortic lymphadenectomy with mean age 60.07 ± 10.67 (range 34.69-83.23) years divided into two groups: one with use of the Vessel Sealer; the second one only with monopolar scissors and subdivided by one-site versus dual docking. Duration of the operation was significantly associated with previous surgery (p < 0.005). Use of the Vessel Sealer was associated with lower blood loss during surgery (p < 0.05). The number of removal pelvic lymph nodes was higher in case of Vessel Sealer with no relation to BMI. Experience in robotic surgery allowed for shortened operation time and led to better outcomes. The Vessel Sealer used in robotic surgery appears to reduce blood loss during surgery and operation time, especially in the case of previous surgery, however, it increases costs of the procedure.

• MeSH
• délka operace MeSH
• dospělí MeSH
• krvácení při operaci prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfadenektomie * metody   MeSH
• nádory endometria * chirurgie   patologie   MeSH
• roboticky asistované výkony * metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: This study aimed to evaluate the association between pre-operative progesterone receptor (PR) and p53 expression and prognosis in pre-operative grade 2 endometrioid endometrial carcinoma compared with grade 1 and grade 3 carcinomas. METHODS: Three European endometrial carcinoma cohort studies were included. Patients with pre-operative grade 2 endometrioid carcinoma and known pre-operative PR and p53 status were included (n = 400), as were patients with pre-operative grade 1 (n = 602) or grade 3 (n = 148) endometrioid carcinomas. Kaplan-Meier and Cox regression analyses were performed to analyze disease-specific and disease-free survival. RESULTS: Patients with pre-operative grade 2 endometrial carcinoma and wild-type p53 plus PR-positive expression showed a similar 7-year disease-specific survival to grade 1 endometrial carcinoma patients (95.8% vs 97.5%, p = .13), while the 7-year disease-specific survival of patients with grade 2 endometrial carcinoma with p53 aberrant and/or negative PR expression (83.5%) was significantly lower (p < .001). The combination of these markers was an independent prognostic factor in multivariate Cox regression analyses. CONCLUSIONS: The prognostic impact of pre-operative p53 and PR expression in patients with grade 2 endometrioid endometrial carcinoma supports a modified binary grading system in which grade 2 patients should be pre-operatively classified as low- or high-grade depending on p53 and PR expression.

• MeSH
• dospělí MeSH
• endometroidní karcinom * patologie   metabolismus   chirurgie   mortalita   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádorový supresorový protein p53 * metabolismus   biosyntéza   MeSH
• nádory endometria * patologie   metabolismus   chirurgie   mortalita   MeSH
• prognóza MeSH
• receptory progesteronu * metabolismus   biosyntéza   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH