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.
- Klíčová slova
- Endometrioid Endometrial Carcinoma, Grade 2, Progesterone Receptor, p53,
- 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
- Názvy látek
- nádorové biomarkery MeSH
- nádorový supresorový protein p53 * MeSH
- receptory progesteronu * MeSH
- TP53 protein, human MeSH Prohlížeč
Endometriosis is a chronic disease characterised by the presence of endometrial tissue outside the uterine cavity, affecting 5-15% of women, especially those of reproductive age. The disease may manifest itself as dysmenorrhoea, dyspareunia, sterility and chronic pelvic pain, among other symptoms. Although it is not malignant, it shares some characteristics with cancer and can lead to epithelial ovarian carcinoma. The risk of malignant transformation of endometriosis is estimated at 1% in premenopausal women and 1-2.5% in postmenopausal women. Our case report describes a 46-year-old female patient with long-standing abdominal pain and a history of surgically confirmed endometriosis. Imaging revealed a cystic mass in the left mesogastrium, which was subsequently surgically removed. Histological examination confirmed the presence of a low-grade endometrioid carcinoma arising from an extragenital endometriosis lesion. Following surgical treatment, the patient underwent adjuvant chemotherapy, after which she was in complete remission. The diagnosis of malignant transformation of endometriosis is complex, requiring a combination of thorough clinical examination, imaging, and histopathological verification. Therapy involves radical surgery and possibly adjuvant chemotherapy, similar to ovarian carcinomas. Despite advances in treatment and research, endometriosis remains a complex disease with unclear aetiology, heterogeneous clinical presentation, and risk of malignant transformation.
- Klíčová slova
- Endometriosis, diagnosis, endometriosis– malignant transformation, extragenital lesion, treatment, type 2 diabetes,
- MeSH
- endometrióza * patologie komplikace MeSH
- endometroidní karcinom * patologie etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorová transformace buněk * patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
BACKGROUND: While total hysterectomy and bilateral salpingo-oophorectomy without lymph node staging are standard for low- and intermediate-risk endometrial cancer, certain histopathologic factors revealed after surgery can necessitate additional interventions. Our study assessed the influence of sentinel lymph node biopsy on postoperative decision-making. MATERIALS AND METHODS: In the SENTRY trial (July 2021 - February 2023), we enrolled patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IA-IB low-grade endometrioid endometrial cancer. Laparoscopic sentinel lymph node mapping using indocyanine green was performed alongside total hysterectomy with bilateral salpingo-oophorectomy. Subsequent management changes based on sentinel lymph node biopsy results were evaluated. The trial was registered at ClinicalTrials.gov (NCT04972682). RESULTS: Of the 100 enrolled participants, a bilateral detection rate of 91% was observed with a median detection time of 10 min (interquartile range 8-13 min). Sentinel lymph node metastases were found in 8% (N = 8) of participants. Postoperative FIGO staging increased in 15% (N = 15) and decreased in 5% (N = 5) of patients. Sentinel lymph node biopsy results altered the adjuvant treatment plan for 20% (N = 20): external beam radiotherapy was omitted in 12% (N = 12) while 6% (N = 6) had external beam radiotherapy +/- systemic chemotherapy added due to sentinel lymph node metastases. In 2% (N = 2), the external beam radiotherapy field was expanded with the paraaortic region. No intraoperative complications were reported and no 30-day major morbidity and mortality occurred. Throughout a median follow-up of 14 (95% CI 12-15 months, neither patient-reported lymphedema nor pelvic recurrence surfaced in the cohort. CONCLUSIONS: Sentinel lymph node biopsy using indocyanine green is a safe procedure and allows tailoring adjuvant therapy in presumed low- and intermediate-risk endometrial cancer. It assists in avoiding external beam radiotherapy overtreatment and introducing additional modalities when necessary.
- Klíčová slova
- Drug therapy, Hysterectomy, Uterine cancer, adjuvant treatment, gynecological cancer, indocyanine green, radiotherapy, sentinel lymph node,
- MeSH
- biopsie sentinelové lymfatické uzliny * MeSH
- endometroidní karcinom patologie chirurgie terapie MeSH
- hysterektomie MeSH
- indokyanová zeleň MeSH
- laparoskopie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- nádory endometria * patologie chirurgie terapie MeSH
- pooperační péče MeSH
- salpingo-ooforektomie MeSH
- senioři MeSH
- staging nádorů MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- Názvy látek
- indokyanová zeleň MeSH
Most bone tumors are metastatic. Breasts, lungs, kidneys, and thyroid are the primary sites most commonly involved in bone metastasis-type outcomes. This case study describes the involvement of a patient with a bone tumor located in the axial skeleton, initially in the sacral region. However, the primary site was undefined. Therefore, it was necessary to expand the investigation with immunohistochemistry, which demonstrated a metastatic tumor compatible with endometrioid adenocarcinoma. But even after examination, no active lesion was found in the endometrial region. The study was observational, descriptive, and aimed to discuss the importance of more specific investigative methods. In this context, immunohistochemistry stands out as an exquisite method capable of optimizing diagnosis, therapy, and consequently, prognosis.
- Klíčová slova
- bone neoplasm, endometrioid adenocarcinoma, immunohistochemistry,
- MeSH
- endometroidní karcinom * patologie sekundární MeSH
- křížová kost * patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory endometria * patologie MeSH
- nádory páteře sekundární diagnostické zobrazování MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
BACKGROUND: IMP2 and IMP3 are mRNA binding proteins involved in carcinogenesis. We examined a large cohort of ovarian tumors with the aim to assess the value of IMP2 and IMP3 for differential diagnosis, and to assess their prognostic significance. METHODS: Immunohistochemical analyses with antibodies against IMP2 and IMP3 were performed on 554 primary ovarian tumors including 114 high grade serous carcinomas, 100 low grade serous carcinomas, 124 clear cell carcinomas, 54 endometrioid carcinomas, 34 mucinous carcinomas, 75 mucinous borderline tumors, and 41 serous borderline tumors (micropapillary variant). The associations of overall positivity with clinicopathological characteristics were evaluated using the chi-squared test or Fisher's Exact test. RESULTS: We found IMP2 expression (in more than 5% of tumor cells) in nearly all cases of all tumor types, so the prognostic meaning could not be analyzed. The positive IMP3 expression (in more than 5% of tumor cells) was most common in mucinous carcinomas (82%) and mucinous borderline tumors (81%), followed by high grade serous (67%) and clear cell carcinomas (67%). The expression was less frequent in endometrioid carcinomas (39%), low grade serous carcinomas (23%), and micropapillary variant of serous borderline tumors (20%). Prognostic significance of IMP3 could be evaluated only in low grade serous carcinomas in the case of relapse-free survival, where negative cases showed better RFS (p = 0.033). CONCLUSION: Concerning differential diagnosis our results imply that despite the differences in expression in the different ovarian tumor types, the practical value for diagnostic purposes is limited. Contrary to other solid tumors, we did not find prognostic significance of IMP3 in ovarian cancer, with the exception of RFS in low grade serous carcinomas. However, the high expression of IMP2 and IMP3 could be of predictive value in ovarian carcinomas since IMP proteins are potential therapeutical targets.
- Klíčová slova
- IMP2, IMP3, Immunohistochemistry, Ovarian carcinoma,
- MeSH
- endometroidní karcinom * patologie MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mucinózní adenokarcinom * diagnóza patologie MeSH
- nádorové biomarkery analýza MeSH
- nádory vaječníků * patologie MeSH
- peritoneální nádory * MeSH
- prekancerózy * MeSH
- serózní cystadenokarcinom * metabolismus MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- IGF2BP2 protein, human MeSH Prohlížeč
- IMP3 protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH
IMPORTANCE: Patients with low-grade (ie, grade 1-2) endometrial cancer (EC) are characterized by their favorable prognosis compared with patients with high-grade (ie, grade 3) EC. With the implementation of molecular profiling, the prognostic relevance of tumor grading might lose attention. As most patients present with low-grade EC and have an excellent outcome, the value of molecular profiling for these patients is unclear. OBJECTIVE: To determine the association of molecular profiling with outcomes among patients with low-grade EC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included a multicenter international European cohort of patients diagnosed with EC between 1994 and 2018, with a median follow-up of 5.9 years. Molecular subgroups were determined by next-generation sequencing using single-molecule molecular inversion probes and by immunohistochemistry. Subsequently, tumors were classified as polymerase epsilon (POLE)-altered, microsatellite instable (MSI), tumor protein p53 (TP53)-altered, or no specific molecular profile (NSMP). Patients diagnosed with any histological subtypes and FIGO (International Federation of Gynecology and Obstetrics) stages of EC were included, but patients with early-stage EC (FIGO I-II) were only included if they had known lymph node status. Data were analyzed February 20 to June 16, 2022. EXPOSURES: Molecular testing of the 4 molecular subgroups. MAIN OUTCOMES AND MEASURES: The main outcome was disease-specific survival (DSS) within the molecular subgroups. RESULTS: A total of 393 patients with EC were included, with a median (range) age of 64.0 (31.0-86.0) years and median (range) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 29.1 (18.0-58.3). Most patients presented with early-stage (290 patients [73.8%]) and low-grade (209 patients [53.2%]) disease. Of all patients, 33 (8.4%) had POLE-altered EC, 78 (19.8%) had MSI EC, 72 (18.3%) had TP53-altered EC, and 210 (53.4%) had NSMP EC. Across all molecular subgroups, patients with low-grade EC had superior 5-year DSS compared with those with high-grade EC, varying between 90% to 100% vs 41% to 90% (P < .001). Multivariable analysis in the entire cohort including age, tumor grade, FIGO stage, lymphovascular space invasion, and the molecular subgroups as covariates found that only high-grade (hazard ratio [HR], 4.29; 95% CI, 2.15-8.53; P < .001), TP53-altered (HR, 1.76; 95% CI, 1.04-2.95; P = .03), and FIGO stage III or IV (HR, 4.26; 95% CI, 2.50-7.26; P < .001) disease were independently associated with reduced DSS. CONCLUSIONS AND RELEVANCE: This cohort study found that patients with low-grade EC had an excellent prognosis independent of molecular subgroup. These findings do not support routine molecular profiling in patients with low-grade EC, and they demonstrate the importance of primary diagnostic tumor grading and selective profiling in low-grade EC to increase cost-effectiveness.
- MeSH
- endometroidní karcinom * patologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory endometria * MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
OBJECTIVE: To evaluate whether the amount of preoperative endometrial tissue surface is related to the degree of concordance with final low- and high-grade endometrial cancer (EC). In addition, to determine whether discordance is influenced by sampling method and impacts outcome. METHODS: A retrospective cohort study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC). Surface of preoperative endometrial tissue samples was digitally calculated using ImageJ. Tumor samples were classified into low-grade (grade 1-2 endometrioid EC (EEC)) and high-grade (grade 3 EEC + non-endometroid EC). RESULTS: The study cohort included 573 tumor samples. Overall concordance between pre- and postoperative diagnosis was 60.0%, and 88.8% when classified into low- and high-grade EC. Upgrading (preoperative low-grade, postoperative high-grade EC) was found in 7.8% and downgrading (preoperative high-grade, postoperative low-grade EC) in 26.7%. The median endometrial tissue surface was significantly lower in concordant diagnoses when compared to discordant diagnoses, respectively 18.7 mm2 and 23.5 mm2 (P = 0.022). Sampling method did not influence the concordance in tumor classification. Patients with preoperative high-grade and postoperative low-grade showed significant lower DSS compared to patients with concordant low-grade EC (P = 0.039). CONCLUSION: The amount of preoperative endometrial tissue surface was inversely related to the degree of concordance with final tumor low- and high-grade. Obtaining higher amount of preoperative endometrial tissue surface does not increase the concordance between pre- and postoperative low- and high-grade diagnosis in EC. Awareness of clinically relevant down- and upgrading is crucial to reduce subsequent over- or undertreatment with impact on outcome.
- Klíčová slova
- Concordant, Diagnosis, Discordant, Endometrial carcinoma, Endometrial sampling, Pathology,
- MeSH
- biopsie metody MeSH
- endometrium patologie MeSH
- endometroidní karcinom * chirurgie patologie MeSH
- lidé MeSH
- nádory endometria * patologie MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy. OBJECTIVE: This study aimed to improve the efficacy of hormonal therapy by relating immunohistochemical expression of estrogen and progesterone receptors and estrogen receptor pathway activity scores to response to hormonal therapy. STUDY DESIGN: Patients with advanced or recurrent endometrial cancer and available biopsies taken before the start of hormonal therapy were identified in 16 centers within the European Network for Individualized Treatment in Endometrial Cancer and the Dutch Gynecologic Oncology Group. Tumor tissue was analyzed for estrogen and progesterone receptor expressions and estrogen receptor pathway activity using a quantitative polymerase chain reaction-based messenger RNA model to measure the activity of estrogen receptor-related target genes in tumor RNA. The primary endpoint was response rate defined as complete and partial response using the Response Evaluation Criteria in Solid Tumors. The secondary endpoints were clinical benefit rate and progression-free survival. RESULTS: Pretreatment biopsies with sufficient endometrial cancer tissue and complete response evaluation were available in 81 of 105 eligible cases. Here, 22 of 81 patients (27.2%) with a response had estrogen and progesterone receptor expressions of >50%, resulting in a response rate of 32.3% (95% confidence interval, 20.9-43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2-64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9-68.9) and 75.0% (95% confidence interval, 62.2-87.8) for a progesterone receptor expression of >50%. The application of the estrogen receptor pathway test to cases with a progesterone receptor expression of >50% resulted in a response rate of 57.6% (95% confidence interval, 42.1-73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20-48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20-52) with an estrogen receptor pathway activity score of >15 had not progressed. CONCLUSION: The prediction of response to hormonal treatment in endometrial cancer improves substantially with a 50% cutoff level for progesterone receptor immunohistochemical expression and by applying a sequential test algorithm using progesterone receptor immunohistochemical expression and estrogen receptor pathway activity scores. However, results need to be validated in the prospective Prediction of Response to Hormonal Therapy in Advanced and Recurrent Endometrial Cancer (PROMOTE) study.
- Klíčová slova
- aromatase inhibitors, estrogen receptor pathway activity, progesterone receptor, progestin therapy,
- MeSH
- alfa receptor estrogenů metabolismus MeSH
- antagonisté estrogenu terapeutické užití MeSH
- doba přežití bez progrese choroby MeSH
- endometroidní karcinom farmakoterapie genetika metabolismus patologie MeSH
- hormonální protinádorové látky terapeutické užití MeSH
- imunohistochemie MeSH
- inhibitory aromatasy terapeutické užití MeSH
- kritéria léčebné odpovědi MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie genetika metabolismus patologie MeSH
- messenger RNA metabolismus MeSH
- nádorové biomarkery metabolismus MeSH
- nádory endometria farmakoterapie genetika metabolismus patologie MeSH
- progestiny terapeutické užití MeSH
- receptory progesteronu metabolismus MeSH
- regulace genové exprese u nádorů genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tamoxifen terapeutické užití MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alfa receptor estrogenů MeSH
- antagonisté estrogenu MeSH
- hormonální protinádorové látky MeSH
- inhibitory aromatasy MeSH
- messenger RNA MeSH
- nádorové biomarkery MeSH
- progestiny MeSH
- receptory progesteronu MeSH
- tamoxifen MeSH
OBJECTIVE: The main objective of the article is to clearly inform healthcare professionals about the newly implemented molecular classification of endometrial cancer into practice. METHODS: Summary of current knowledge, recommendations and new procedures relating to molecular genetic examination of the tissues of patients with endometrial carcinoma. RESULTS: Endometrial cancer is currently dia-gnosed on the base of histopathological morphology. According to the classical Bokhman division, we distinguish between two relatively wide groups of tumors which are different in pathogenesis: type I - estrogen-dependent tumors, clinically usually indolent, and type II - non-endometroid tumors, clinically aggressive, without dependence on estrogen stimulation. This classification fulfills a didactic purpose and provides easy orientation for epidemiological data, but is not suitable for stratification due to the overlap of clinical, pathological and molecular features. The Cancer Genome Atlas project classifies endometrial tumors into 4 groups based on molecular genetic features. CONCLUSION: Integration of the histopathological findings along with molecular classification appears to be the best approach for evaluating each individual tumor. This will help to achieve the ideal stratification of patients for treatment regimens.
- Klíčová slova
- Endometrial carcinoma, POLE mutation –mismatch repair-deficient tumors, TP53 mutation, The Cancer Genome Atlas project, endometrial (endometrioid) carcinoma, molecular classification, non-specific molecular profile,
- MeSH
- endometroidní karcinom * MeSH
- lidé MeSH
- mutace MeSH
- nádory endometria * genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The goal of this manuscript is to provide an overview of the significance of immunohistochemical methods in diagnosing endometrial carcinoma. The main points discussed include: the use of immunohistochemistry in the differential diagnosis of the main histological types of endometrial carcinoma, the difference between primary serous endometrial carcinoma and the involvement with high grade serous carcinoma of another primary source, the diagnosis of undifferentiated/dedifferentiated endometrial carcinoma, and diagnosing tumours with neuroendocrine differentiation. The role of p53 expression evaluation is also emphasized as a special area of interest, not only in the context of differential diagnosis, but also from the point of view of the prognosis and prediction of endometrial carcinoma as an ancillary marker for subtypization of these tumours.
- Klíčová slova
- Endometrial carcinoma, clear cell carcinoma, endometrial cancer, endometrioid carcinoma, immunohistochemistry, serous carcinoma, undifferentiated / dedifferentiated carcinoma,
- MeSH
- diferenciální diagnóza MeSH
- endometroidní karcinom * diagnóza MeSH
- imunohistochemie MeSH
- lidé MeSH
- nádorové biomarkery MeSH
- nádory endometria * diagnóza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- nádorové biomarkery MeSH