Impact of adjuvant therapy on oncologic outcomes in uterine-confined clear cell carcinoma of the endometrium.

OBJECTIVES: To determine the impact of adjuvant therapy on oncologic outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, or II endometrial clear cell carcinoma (ECCC). METHODS: We conducted a retrospective review at 4 international institutions. Patients with newly diagnosed clinical stage I or II disease of either clear cell or mixed histology with a clear cell component treated between 01/01/2000-12/31/2015 were included. Oncologic outcomes were assessed for patients based on adjuvant treatment received, including chemotherapy, radiation, or chemotherapy with radiation. RESULTS: Of 125 patients identified and analyzed, 77 (61.6%) had clear cell histology and 118 (94.4%) had stage I disease. Median age at diagnosis was 65 years (range, 33-91). All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. Twenty-five patients (20.0%) underwent surgical management alone and 100 (80.0%) received adjuvant therapy: 20 (16.0%) received postoperative chemotherapy, 47 (37.6%) received postoperative radiation, and 33 (26.4%) received postoperative chemotherapy with radiation. Median follow-up was 88.4 months (range, <1-234). Progression-free survival (PFS) or overall survival (OS) did not significantly differ between surgery alone and type of adjuvant therapy (P = 0.18 and P = 0.56, respectively). Patients with mixed ECCC did not have a survival advantage over those with pure ECCC (5-year PFS rate, 85.0% vs 82.7%, P = 0.77; 5-year OS rate, 88.3% vs 91.2%, P = 0.94). CONCLUSIONS: Receipt of adjuvant therapy in surgically staged I/II ECCC did not appear to offer a survival advantage over observation alone. Adjuvant therapy in early-stage ECCC with consideration of molecular classification should be evaluated.

Endometrial carcinomas with ambiguous histology often harbor TP53 mutations.

The objective of the present study was to characterize the molecular features of endometrial carcinomas with ambiguous histology. Eighteen carcinomas that could not be conclusively typed based on morphology and immunohistochemistry underwent analysis of mismatch repair (MMR) status, microsatellite status, and whole-exome sequencing. None of the tumors had pathogenic POLE mutation. Twelve tumors (67%) were microsatellite stable, and 6 (33%) had microsatellite instability. Fourteen tumors (78%) harbored TP53 mutations, and 2 (11%) had mutations in MMR genes. Eleven carcinomas (61%) were classified as copy number high and 7 (39%) as MSI-hypermutated, the latter including 3 tumors with TP53 mutation who concomitantly had MSI or mutation in a MMR gene. Other mutations that were found in > 1 tumor affected MUC16 (7 tumors), PIK3CA (6 tumors), PPP2R1A (6 tumors), ARID1A (5 tumors), PTEN (5 tumors), FAT1 (4 tumors), FAT4 (3 tumors), BRCA2 (2 tumors), ERBB2 (2 tumors), FBXW7 (2 tumors), MET (2 tumors), MTOR (2 tumors), JAK1 (2 tumors), and CSMD3 (2 tumors). At the last follow-up (median = 68.6 months), 8 patients had no evidence of disease, 1 patient was alive with disease, 8 patients were dead of disease, and 1 patient died of other cause. In conclusion, based on this series, the molecular landscape of endometrial carcinomas with ambiguous histology is dominated by TP53 mutations and the absence of POLE mutations, with heterogeneous molecular profile with respect to other genes. A high proportion of these tumors is clinically aggressive.

Comprehensive molecular characterization of early stage grade 3 endometrioid endometrial adenocarcinoma.

OBJECTIVE: The treatment for stage IB grade 3 endometrioid endometrial adenocarcinoma is challenging with variable practice. Molecular characterization may help identify adjuvant therapy strategies beyond stage. We aimed to better understand the molecular features of these tumors by characterizing them by ProMisE classification, mutational signature, and commonly mutated genes. METHODS: Patients with stage IB grade 3 EEC at two institutions were included. Immunohistochemistry and whole exome sequencing were performed on archival FFPE tissue sections to determine ProMisE classification. Personal Cancer Genome Reporter was used for somatic variant annotation, and mutational signatures were generated based on COSMIC single base substitution mutational signatures. RESULTS: 46 patients were included with variable adjuvant treatment. Nine patients recurred (19.6%), most with extra-abdominal disease (n = 5, or 55.6%). 10 had POLE mutations (21.7%), 18 were MMR deficient (39.1%), 6 had abnormal p53 (13.0%), and 12 were p53 wildtype (26.1%). There were no recurrences in the POLE subgroup. A dominant mutational signature was identified in 38 patients: 17 SBS5 signature (44.7%), 10 SBS15 or SBS44 signature (26.3%), 7 SBS10a or SBS10b signature (18.4%), 3 SBS14 signature (7.9%), and 1 SBS40 signature (2.6%). The six patients that recurred had a SBS5 signature. Frequently mutated genes included ARID1A (n = 30, 65%), PTEN (n = 28, 61%), MUC16 (n = 27, 59%), and PIK3CA (n = 25, 54%). CONCLUSIONS: This comprehensive evaluation found a molecularly diverse cohort of tumors, despite the same histology, stage and grade. Mutational signature SBS5 correlated with a high risk of recurrence. Further refining of endometrial cancer classification may enable more precise patient stratification and personalized treatment approaches.

Fertility-sparing treatment and follow-up in patients with cervical cancer, ovarian cancer, and borderline ovarian tumours: guidelines from ESGO, ESHRE, and ESGE.

The European Society of Gynaecological Oncology, the European Society of Human Reproduction and Embryology, and the European Society for Gynaecological Endoscopy jointly developed clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing strategies and follow-up of patients with cervical cancers, ovarian cancers, and borderline ovarian tumours. The developmental process of these guidelines is based on a systematic literature review and critical appraisal involving an international multidisciplinary development group consisting of 25 experts from relevant disciplines (ie, gynaecological oncology, oncofertility, reproductive surgery, endoscopy, imaging, conservative surgery, medical oncology, and histopathology). Before publication, the guidelines were reviewed by 121 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover oncological aspects of fertility-sparing strategies during the initial management, optimisation of fertility results and infertility management, and the patient's desire for future pregnancy and beyond.

2009 International Federation of Gynecology and Obstetrics (FIGO) stage IIIA endometrial cancer: oncologic outcomes based on involvement of adnexa, serosa, or both.

OBJECTIVE: To assess clinicopathologic features and survival outcomes of patients with endometrial carcinoma involving adnexal, full-thickness serosal, or combined involvement. METHODS: This international, multi-institutional, retrospective study examined patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IIIA endometrial cancer and tumors involving the uterine serosa and/or adnexa, who were surgically staged between 2000 and 2019. Patients with sarcoma histology, concurrent endometrial/ovarian malignancy, neoadjuvant treatment, positive lymph nodes, or peritoneal disease were excluded. RESULTS: Of 185 patients identified, 139 had tumors with adnexal-only, 40 with serosal-only, and six with combined adnexal/serosal involvement. Median age at diagnosis was 60 years (range 23-89). Among tumors of endometrioid histology, 12 (48%) with serosal-only and 17 (19%) with adnexal-only involvement were FIGO grade 3 (p=0.007). Twenty-three tumors with serosal-only (64%) and 50 with adnexal-only (37%) involvement had lymphovascular invasion (p=0.004). Non-endometrioid histology was present in five tumors (83%) with combined adnexal/serosal, 15 (38%) with serosal-only, and 50 (36%) with adnexal-only involvement.Median follow-up was 77 months (range 0.6-254). Five-year progression-free survival and overall survival rates for all patients with stage IIIA disease were 73.8% (SE 3.5%) and 81.0% (SE 3.1%), respectively. For patients with adnexal-only, serosal-only, and combined adnexal/serosal involvement, 5-year progression-free survival rates were 80% (SE 3.8%), 61% (SE 8.3%), and 33% (SE 19.2%), respectively (p<0.01); 5-year overall survival rates were 85% (SE 3.3%), 70% (SE 7.8%), and 60% (SE 21.9%), respectively (p=0.09). On univariate analysis, tumors having serosal involvement with/without adnexal involvement, non-endometrioid histology, and lymphovascular invasion were significantly associated with progression. On multivariate analysis, tumors having serosal involvement with/without adnexal involvement remained significantly associated with recurrence (adjusted HR=2.2, 95% CI 1.2 to 4.3; p=0.01). CONCLUSIONS: Patients with 2009 FIGO stage IIIA endometrial cancer have distinct survival outcomes depending upon adnexal and/or serosal involvement. Progression-free survival was worse for patients with serosal involvement after adjusting for histology, adjuvant treatment, and lymphovascular space invasion.

Oncologic outcomes based on lymphovascular space invasion in node-negative FIGO 2009 stage I endometrioid endometrial adenocarcinoma: a multicenter retrospective cohort study.

BACKGROUND: The 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system includes lymphovascular invasion quantification as a staging criterion for endometrioid endometrial carcinomas; no lymphovascular invasion and focal invasion (≤4 vessels involved) are grouped as one category, and substantial invasion as another. OBJECTIVE: To assess the association between lymphovascular invasion and oncologic outcomes. METHODS: We retrospectively identified patients with FIGO 2009 stage I endometrioid endometrial cancer treated surgically with total hysterectomy and lymph node assessment at two tertiary care centers between January 1, 2012, and December 31, 2019. Lymphovascular space invasion was categorized as focal (<5 vessels involved), substantial (≥5 vessels involved), and no lymphovascular invasion using WHO criteria. RESULTS: Of 1555 patients included, 65 (4.2%) had substantial, 119 (7.7%) had focal, and 1371 (88.2%) had no lymphovascular invasion. Median age was 64 years (range 24-92). Thirty-five patients (53.8%) with substantial, 44 (37%) with focal, and 115 (8.4%) with no lymphovascular invasion had stage IB disease (p<0.001); 21 (32.3%) with substantial, 24 (20.2%) with focal, and 91 (6.6%) with no lymphovascular invasion had grade 3 disease (p<0.001). Thirty-six patients (55.4%) with substantial, 80 (67.2%) with focal, and 207 (15.1%) with no lymphovascular invasion received adjuvant treatment (p<0.001). Median follow-up was 61.5 months (range 0.8-133.9). Five-year progression-free survival rates were 68.7% (substantial), 70.5% (focal), and 90.7% (no invasion) (p<0.001). On multivariate analysis, any lymphovascular invasion was associated with increased risk of progression/death (adjusted HR (aHR)=1.84 (95% CI 1.73 to 1.96) for focal; 2.17 (95% CI 1.96 to 2.39) for substantial). Compared with focal, substantial lymphovascular invasion was associated with an aHR for disease progression of 1.18 (95% CI 1.00 to 1.39). CONCLUSIONS: Focal and substantial lymphovascular invasion were associated with increased risk of disease progression and do not appear to be prognostically distinct. Focal versus no lymphovascular invasion have different prognostic outcomes and should not be combined into one category.

Hormone Receptor Expression and Activity for Different Tumour Locations in Patients with Advanced and Recurrent Endometrial Carcinoma.

BACKGROUND: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. METHODS: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0-10%, 10-50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. RESULTS: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. CONCLUSIONS: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future.

Molecular characteristics of tubo-ovarian carcinosarcoma at different anatomic locations.

Carcinosarcoma (CS) is an uncommon and clinically aggressive malignancy. The objective of the present study was to characterize the molecular features of CS at various anatomic locations, including serous effusions. Specimens (n = 32) consisted of 25 biopsies/surgical resection specimens and 7 serous effusions (6 peritoneal, 1 pleural) from 25 patients. Fresh-frozen cell pellets and surgical specimens underwent targeted next-generation sequencing covering 50 unique genes. A total of 31 mutations were found in 25 of the 32 tumors studied, of which 1 had 3 mutations, 4 had 2 different mutations, and 20 had a single mutation. The most common mutations were in TP53 (n = 25 in 24 tumors; 1 tumor with 2 different mutations), with less common mutations found in RB1 (n = 2), MET (n = 1), KRAS (n = 1), PTEN (n = 1), and KIT (n = 1). Patient-matched specimens harbored the same TP53 mutation. Tumors with no detected mutations were more common in serous effusion specimens (3/7; 43%) compared with surgical specimens (4/25; 16%). In conclusion, the molecular landscape of CS is dominated by TP53 mutations, reinforcing the observation that the majority of these tumors develop from high-grade serous carcinoma. Whether CS cells in serous effusions differ from their counterparts in solid lesions remains uncertain.

Surgery for Recurrent Epithelial Ovarian Cancer.

PURPOSE OF REVIEW: To review evidence around the value and challenges of surgery for recurrent epithelial ovarian cancer (ROC). Both cytoreductive and palliative aspects will be addressed RECENT FINDINGS: Prospective and retrospective evidence demonstrates a significantly longer remission derived from the combination of surgical and systemic modalities as opposed to systemic treatment alone in carefully selected ROC-patients who have relapsed more than 6 months from the end of their 1st line platinum-based chemotherapy. Nevertheless, this benefit appears to be limited when total macroscopic tumor clearance is not achieved. Selection algorithms to identify optimal surgical candidates are of paramount importance to prevent surgical morbidity without the equivalent oncological benefit. In the palliative setting, the risks and benefits of salvage surgery need to be counterbalanced with the advances of conservative techniques for optimal care. Well-defined selection algorithms to identify those who will benefit from surgery in the relapsed setting appear to be the key to oncologic and surgical success.

Associations between modifiable lifestyle factors and health-related quality of life among endometrial carcinoma survivors - A cross-sectional study.

OBJECTIVE: To explore possible associations between modifiable lifestyle factors and health-related quality of life (HRQoL) in endometrial carcinoma survivors by assessing differences in HRQoL between survivors meeting and not meeting the World Health Organization's (WHO) recommendations regarding physical activity, BMI, and smoking. METHODS: This was a cross-sectional population-based study in women having undergone surgery for assumed early-stage endometrial carcinoma. Thresholds for clinical importance based on the EORTC QoL working group were used to interpret scores. Effect size (ES) was interpreted as small (d = 0.2-0.49), medium (d = 0.5-0.8), and large (d > 0.8). RESULTS: In total, 1200 evaluable women were included. Meeting physical activity recommendations and BMI <25 kg/m2 was associated with significantly better global health status, (ES) = 0.18 and ES = -0.11, respectively. On multivariate analysis, women meeting physical activity recommendations had significantly higher scores on physical- (ES = 0.31), role- (ES = 0.15), and social functioning (ES = 0.15), and lower levels of fatigue (ES = -0.16), pain (ES = -0.10), and appetite loss (ES = -0.15) (all p < 0.05) compared to non-meeting survivors. Participants with BMI ≥25 kg/m2 had lower scores for social functioning (ES = -0.10), and higher levels of pain (ES = 0.13) and dyspnea (ES = 0.12) (all p < 0.05) compared to those with BMI <25 kg/m2. Smokers had lower scores for emotional functioning (ES = -0.09) and higher levels of diarrhea (ES = 0.10) (all p < 0.05) compared to non-smokers. CONCLUSION: Meeting WHO recommendations for modifiable life-style factors is associated with better HRQoL among endometrial carcinoma survivors: Being sufficiently physical active and having a BMI <25 kg/m2 are significantly associated with better self-reported global health status. All modifiable factors are associated with better functioning, and reduced symptom-burden.

Self-reported lower extremity lymphedema and quality of life after surgical staging of endometrial carcinoma: A population based cross-sectional study.

OBJECTIVES: Sentinel lymph node biopsy (SLN) has replaced lymphadenectomy in staging of endometrial carcinoma. The aims of the study were to explore the prevalence of self-reported lymphedema (LEL), identify factors associated with LEL, compare quality of life (QoL) scores using thresholds of clinical importance, and assess correlation between different questionnaires. METHODS: Women who underwent staging for endometrial carcinoma from 2006 to 2021 were invited to complete the Lower Extremity Lymphedema Screening Questionnaire (LELSQ), EORTC QLQ-C30, QLQ-EN24 and EQ-5D-5L. RESULTS: Of 2156 invited survivors, 61% participated in the study, whereof 1127 were evaluable by LELSQ. The LEL prevalence was 51%, 36% and 40% after lymphadenectomy, SLN and hysterectomy, respectively (p < 0.001). Higher BMI, undergoing lymphadenectomy and receiving adjuvant chemotherapy were associated with LEL; odds ratios 1.07 (95% CI 1.05-1.09), 1.42 (95% CI 1.03-1.97) and 1.43 (95% CI 1.08-1.89) respectively. QoL was lower for women with LEL compared to those without. In women with musculoskeletal complaints the prevalence of LEL was 59%, 50% and 53% after lymphadenectomy, SLN and hysterectomy (p = 0.115), respectively, compared to 39%, 17% and 18% (p < 0.001) in women without musculoskeletal complaints. Spearman's correlation was moderate to strong between the questionnaires. CONCLUSION: SLN implementation is not associated with increased LEL prevalence compared to hysterectomy alone, but is associated with a significantly lower prevalence compared to lymphadenectomy. LEL is associated with lower QoL. Our study demonstrates moderate to strong correlation between self-reported LEL and QoL scores. Available questionnaires may not distinguish between symptoms caused by LEL and musculoskeletal disease.

Social media ambassadors and collaboration with OncoAlert: a European Network of Young Gynae Oncologists study of comparative Twitter analysis of #ESGO2021 and #ESGO2022.

OBJECTIVE: The primary objective was to reveal the impact of social media ambassadors and the collaboration between the European Society of Gynaecological Oncology (ESGO) and the OncoAlert Network on Twitter during the ESGO 2022 Congress by comparing it with the ESGO 2021 Congress. We also aimed to share our experience on how to organize a social media ambassador program and evaluate the potential benefits for the society and the ambassadors. METHODS: We defined the impact as promoting the congress, sharing the knowledge, change in follower count, and change in tweet, retweet, and reply counts. We used the Academic Track Twitter Application Programming Interface to retrieve data from ESGO 2021 and ESGO 2022. We used the keywords of ESGO2021 and ESGO2022 to retrieve data for each of the conferences. The time range in our study captured interactions from before, during, and after conferences. We collected the ambassadors', ESGO's, and the European Network of Young Gynae Oncologists' (ENYGO's) follower data on Twitter from November 2021 to November 2022 for comparative analysis. RESULTS: There was a 7.23-fold increase in the use of the official congress hashtag in 2022 compared with 2021. Compared with #ESGO2021 data, the main interventions of the Social Media Ambassadors and OncoAlert partnership determined 7.79-, 17.36-, 5.50-, 10.58-, and 8.50-fold increases with #ESGO2022 data in the mentions, mentions in retweet, tweet, retweet, and replies, respectively. Similarly, all other most commonly used hashtags in the top 10 list indicated a range from 2.56- to 7.00-fold increase. Compared to the ESGO 2021 congress month, ESGO and the majority (83.3%, n=5) of ambassadors gained more followers during ESGO 2022 congress month. CONCLUSIONS: An official social media ambassadors program and collaboration with influential accounts in the field of interest are beneficial for congress-related engagement on a social media platform (Twitter). Individuals participating in the program can also benefit from gaining higher visibility among specific audience.

Translation and cross-cultural adaptation of the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire.

OBJECTIVE: There is a paucity of international data regarding self-reported lower extremity lymphedema and quality of life after surgery for gynecological cancer. Validated questionnaires are emerging, but translated versions are lacking. Cross-cultural adaptation is important to reduce the risk of introducing bias into a study. OBJECTIVE: To translate and culturally adapt the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire for a Norwegian population. METHODS: Permission to use the original English versions of the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire for translation was obtained. The questionnaires were translated using a procedure based on standard guidelines, including forward translation by native speakers of the target language, synthesis, back translation, and review. Seventeen patients from the Norwegian Radium Hospital gynecological cancer outpatient clinic, all expected to have stable disease, were invited for questionnaire test-retest by completing the same questionnaires twice at 3-4-week intervals. Internal consistency was assessed by calculating Cronbach's alpha. Test-retest reliability was assessed using an intra-class correlation coefficient. RESULTS: Twelve patients completed the questionnaires twice. Cronbach's alpha was 0.75 for the Gynecologic Cancer Lymphedema Questionnaire and 0.89 for the Lower Extremity Lymphedema Screening Questionnaire. The intra-class correlation coefficient was 0.86 for the Gynecologic Cancer Lymphedema Questionnaire and 0.91 for the Lower Extremity Lymphedema Screening Questionnaire. CONCLUSIONS: Translation and cross-cultural adaptation of these internationally validated patient-reported outcomes questionnaires for survivors of lower extremity lymphedema in gynecological cancer was feasible. The Norwegian translation of the Gynecologic Cancer Lymphedema Questionnaire and the Lower Extremity Lymphedema Screening Questionnaire showed acceptable internal consistency and the test-retest reliability was excellent.

Adjuvant therapy in women with early stage uterine serous carcinoma: A multi-institutional study.

OBJECTIVE: Uterine serous carcinoma is a rare but aggressive subtype of endometrial adenocarcinoma. Our objective was to compare adjuvant treatment strategies for patients with early stage uterine serous carcinoma. METHODS: This multi-institutional, retrospective cohort study evaluated patients with early stage uterine serous carcinoma. Patients with FIGO Stage IA-II disease after surgery, whose tumors had serous or any mixed serous/non-serous histology were included. Patients with carcinosarcoma were excluded. Clinical data were abstracted from local medical records. Summary statistics, Fisher's exact, and Kruskal-Wallis tests were used to analyze demographic and clinical characteristics. Univariable and multivariable analyses were performed for recurrence-free and overall survival. RESULTS: There were 737 patients included. Most patients had Stage IA disease (75%), 49% of which had no myometrial invasion. Only 164 (24%) tumors had lymphatic/vascular space invasion. Adjuvant treatment varied: 22% received no adjuvant therapy, 17% had chemotherapy alone, 19% had cuff brachytherapy, 35% had cuff brachytherapy with chemotherapy, and 6% underwent pelvic radiation. Adjuvant treatment was significantly associated with a decreased risk of recurrence (p = 0.04). Compared with no adjuvant therapy, patients who received brachytherapy or brachytherapy/chemotherapy had improved recurrence-free survival (HR 0.59, 95% CI 0.40-0.86; HR 0.65, 95% CI 0.49-0.88, respectively) and overall survival (HR 0.53, 95% CI 0.35-0.79; HR 0.49, 95% CI 0.35-0.69, respectively). Improved survival with brachytherapy and brachytherapy/chemotherapy persisted on multivariable analyses. Chemotherapy alone was also associated with improved overall survival compared with no adjuvant treatment (HR 0.55, 95% CI 0.37-0.81). CONCLUSIONS: Adjuvant therapy was associated with a decreased risk of recurrence relative to observation alone. Adjuvant cuff brachytherapy with and without chemotherapy was associated with improved survival outcomes in patients with early stage uterine serous carcinoma.

Endometrial Carcinoma: Molecular Cytogenetics and Transcriptomic Profile.

Endometrial carcinomas (ECs) are histologically classified as endometrioid and nonendometrioid tumors, with each subgroup displaying different molecular profiles and clinical outcomes. Considerable biological and clinical heterogeneity exists within this scheme, however, reflecting its imperfection. We aimed to gather additional data that might help clarify the tumors' pathogenesis and contribute toward a more meaningful classification scheme. In total, 33 ECs were examined for the presence of chromosomal aberrations, genomic imbalances, pathogenic variants, microsatellite instability, and expression profiles at both gene and miRNA levels. Chromosome 1 was the most frequently rearranged chromosome, showing a gain of all or part of the long arm. Pathogenic variants were found for PTEN (53%), PDGFRA (37%), PIK3CA (34%), and KIT (31%). High microsatellite instability was identified in 15 ECs. Comparing tumors and controls, we identified 23 differentially expressed genes of known importance in carcinogenesis, 15 genes involved in innate and adaptative immune responses, and altered expression of 7 miRNAs. miR-32-5p was the most upregulated. Our series showed a high degree of heterogeneity. Tumors were well-separated from controls, but there was no clear-cut separation between endometrioid and nonendometrioid ECs. Whether this means that the current phenotypic classification is of little relevance or if one still has not detected which genomic parameters to enter into correlation analyses remains unknown.

Nonepithelial ovarian cancer - the current clinical practice in the Nordic countries. Survey from the surgical subcommittee of the Nordic society of gynecological oncology (NSGO).

BACKGROUND: Nonepithelial ovarian cancer (NEOC) represents a wide variety of rare tumors. They are often diagnosed at an early stage and have a good prognosis compared to epithelial ovarian cancer. In the Nordic countries, the total annual number of patients diagnosed with ovarian cancer, Fallopian tube cancer or primary peritoneal carcinoma (hereafter ovarian cancer) was 2281 in 2014-2018, of which 3-10% were NEOC. International guidelines for diagnosis, treatment and follow-up have been developed. We present the results of a survey, aiming at clarifying current clinical practice in the Nordic countries. MATERIAL AND METHODS: Between 09.2020 and 02.2021 a 33-question electronic survey was distributed to 22 hospitals in Finland, Sweden, Norway, Iceland and Denmark via the Nordic Society of Gynecological Oncology (NSGO) National Representatives. Data were collected in a secure web-based software platform. The questionnaire focused on demographics, diagnosis, treatment and follow-up programs. RESULTS: Twenty-one (95,4%) centers completed the survey. A total of 155 annual new NEOC cases treated in the Nordic countries were reported, corresponding to approximately 7% of all ovarian cancer cases. Most centers measured some or all of the recommended biomarkers routinely. Vaginal ultrasound and computed tomography (CT) were the preferred imaging modalities. The majority of centers conducted multidisciplinary team (MDT) meetings. The primary reported treatment was surgery. In 65% of centers, lymph node dissection was only performed in cases with suspicious lymph nodes. Surveillance was usually offered > four years. DISCUSSION: Despite, the presence of clinical European guidelines, variation in the current clinical practice amongst participating centers adhering to national guidelines was observed. Prospective clinical national research programs are sparse, and an enhanced cooperation in the Nordic countries toward development of a Nordic guideline and database is highly warranted and a prerequisite for future research, preferably in cooperation with the larger international groups.