bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stem-like markers in the circulating tumor cells assessment in ovarian cancer.
Authors: Gening Snezhanna , Abakumova Tatyana , Antoneeva Inna , Gening Tatyana 
Published: June 2021

e17542 Background: Circulating tumor cells (CTCs) are a potential source of dissemination and relapse in ovarian cancer (OC). Stem cell properties can provide a survival advantage for CTCs. The clinical significance of stem-like CTCs in OC remains to be studied. We aimed to assess the quantities of the stem, epithelial, mesenchymal CTCs and their relationships with the clinical parameters in the OC. Methods: Peripheral blood samples (7.5 ml) were obtained from patients with primary epithelial OC before treatment. CTCs were isolated by flow cytometry (Cytoflex S (Beckman Coulter, USA)) using antibodies to CD45 (BioLegend, USA); CD44 (BioLegend, USA), CD133 (Miltenyi biotec, Germany), ALDH (Stemcell, Canada) to detect the stem markers; EpCAM (BioLegend, USA), cytokeratins 8, 18 (Abcam plc., UK), vimentin (BioLegend, USA) for epithelial and mesenchymal markers. Blood samples from patients with benign ovarian tumors served as a control. Informed voluntary consent was obtained from all the women. Statistical processing included Mann-Whitney U-test, linear regression, Cox proportional hazards model for progression-free survival (PFS) (Statistica 13.0 (TIBCO, USA)). Results: The study included 30 patients, median age 64 (34-76) years. 15 patients had a FIGO stage IV, 12 - stage III, 1 – stage II and 1 – stage I. The content of CTCs populations is presented in the table. The CTCs counts did not differ depending on age, platelet count, and stage 3 or 4. The amount of CD45-CK+Vim- was higher in the presence of ascites (p = 0.035). We found a regression relationship between the serum CA-125 and the number of CD45-CD44+CD133+ (R2= 0.220, p = 0.016); the leukocyte count in blood and CD45-CD44+ALDHhigh (R2= 0.234, p = 0.017); the number of CD45-Vim+ and CD45-CD44+CD133+ALDH+ (R2= 0.305, p = 0.014); CD45-CK-Vim+ and CD45-EpCAM+CK+ (R2= 0.717, p < 0.001). The Cox regression model for PFS included the number of CD45-CD44+CD133+ALDH+ (HR 1.51 95% CI 1.01-2.24 p = 0.043) and the cytoreductive surgery performance (HR 0.09 95% CI 0.01-0.89 p = 0.039) during the first line of treatment. Conclusions: Various populations of circulating tumor cells coexist in ovarian cancer patients. The use of a combination of stem markers in the CTCs detection can increase their prognostic value in OC. This work was supported by the RFBR grant No. 19-315-90011.[Table: see text]
Classification of molecular subtypes of high-grade serous ovarian cancer by MALDI-Imaging.
Authors: Kassuhn Wanja Nikolai , Klein Oliver , Darb-Esfahani Silvia , Lammert Hedwig , Handzik Sylwia , Taube Eliane T , Schmitt Wolfgang D , Dorigo Oliver , Horst David , Keunecke Carlotta , Dreher Felix , George Joshy , Bowtell David , Hummel Michael , Sehouli Jalid , Blüthgen Nils , Kulbe Hagen , Braicu Elena Ioana 
Published: June 2021

e17544 Background: High-grade serous ovarian cancer (HGSOC) can be separated by gene expression profiling into four molecular subtypes with clear correlation of the clinical outcome. However, these gene signatures have not been implemented in clinical practice to stratify patients for targeted therapy. This is mainly due to a lack of easy, cost-effective and reproducible methods, as well as the high heterogeneity of HGSOC. Hence, we aimed to examine the potential of unsupervised matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) to stratify patients, which might benefit from targeted therapeutic strategies. Methods: Molecular subtyping of paraffin-embedded tissue samples from 279 HGSOC patients was performed by NanoString analysis (ground truth labeling). Next, we applied MALDI-IMS, a novel technology to identify distinct mass profiles on the same paraffin-embedded tissue sections paired with machine learning algorithms to identify HGSOC subtypes by proteomic signature. Finally, we devised a novel strategy to annotate spectra of stromal origin. Results: We elucidated a MALDI-derived proteomic signature (135 peptides) able to classify HGSOC subtypes. Random forest classifiers achieved an area under the curve (AUC) of 0.983. Furthermore, we demonstrated that the exclusion of stroma associated spectra provides tangible improvements to classification quality (AUC = 0.988). False discovery rates (FDR) were reduced from 10.2% to 8.0%. Finally, novel MALDI-based stroma annotation achieved near-perfect classifications (AUC = 0.999, FDR < 1.0%). Conclusions: Here, we present a concept integrating MALDI-IMS with machine learning algorithms to classify patients according to distinct molecular subtypes of HGSOC. This has great potential to assign patients for targeted therapies.
Integrating the genomic and TCR repertoire signatures predicts prognosis in primary epithelial ovarian cancer.
Authors: Xiang Yang , Zhu Shan , Cao Dongyan , Wan Xi-Run , Zhang Chunliu , Yang Junjun , Yang Jiaxin , Yu Mei , Zhang Ying , Ren Tong , Wang Jing , Li Peiling , Zhang Guo-Nan , Bai Jing , Guan Yanfang , Xia Xuefeng 
Published: June 2021

e17547 Background: Epithelial ovarian cancer is one of the common causes of gynecologic cancer death around the world. Histologically, EOC is classified into 5 major sub-types: high-grade serous (HGSOC), low grade serous (LGSOC), clear cell (CCOC), endometrioid (ENOC) and mucinous (MOC). Baseline genomic and immunomicroenvironmental characteristics of treatment-naive patients may offer an insight into recurrent risks. Methods: 101 patients with treatment-naive EOC were enrolled, including 60 HGSOC, 14 LGSOC, 8 ENOC, 14 CCOC, 5 MOC. Tumor tissues and paired peripheral blood samples were collected and performed with target sequencing of 1021 genes and TCR repertoire sequencing. Patients were intensively followed up for at least one year. To explored the molecular characteristic among 5 sub-types, genomic features and TCR repertoire signature were evaluated. Results: The mutation rate of PTEN loss was comparable among 5 sub-types for 53.3% (32/60) in HGSOC, 57.1% (8/14) in LGSOC, 42.9% (6/14) in CCOC, 50% (4/8) in ENOC, 40% (2/5) in MOC. Patients with PTEN loss tended to have lower tumor mutation burden (p = 0.077, Wilcoxon test), especially in HGSOC (p = 0.048, Wilcoxon test). Patients with CCOC and ENOC had significantly higher clonality, which indicates T cell expansion, than SOC tumor (HGSOC, LGSOC) (p = 0.036, Wilcoxon test). Moreover, the proportion of top 10, top 50 and top 100 T cell clones were all significantly higher in CCOC and ENOC than that in SOC(p = 0.0072, 0.0041, 0.0058, Wilcoxon test).In addition, richness and Shannon-index, two metrics for T cell diversity, were significantly higher in SOC comparing with CCOC and ENOC(p = 0.032, 0.0018, Wilcoxon test). After integrated the genomic and TCR features, more favorite disease-free survival (DFS) was found in patients with PTEN loss wild type, higher TMB, higher clonality and lower Shannon-index (p = 0.041, HR = 0.24, Mantel–Cox test). Conclusions: Our results highlight the traits of genomic and TCR repertoire in different subtypes of epithelial ovarian cancer and their prognostic significance. Interestingly, higher T cell clonality in CCOC and ENOC patients were found, which suggested the anti-cancer immune response was better activated. However, our study gets a preliminary result, and further verification work is needed.
Evaluation of immunohistochemical expression of mismatch repair proteins in endometrioid and seromucinous borderline ovarian tumors a 10-year experience in a large health care institution.
Authors: Chavarria Hector , Frimer Marina , Kauff Noah D. , John Veena S. , Khutti Seema 
Published: June 2021

e17557 Background: Borderline tumors (BT) are atypical proliferation of epithelium in the ovary in the absence of destructive stromal invasion, representing for 15% of all epithelial ovarian cancers. [1] Around 10% of the ovarian tumors are hereditary, and approximately 10% of all the hereditary forms of epithelial ovarian tumors are result of a loss of DNA mismatch repair (MMR). [2] Endometrioid borderline tumor (EBT) and Seromucinous borderline tumors (SMBT) are rare tumors in ovary and there is limited literature available on immunohistochemical (IHC) expression of Mismatch repair proteins(MMRP)in these tumors.[3, 4] The aim of this study is to evaluate IHC expression of MMRP in EBT and SMBT of ovary. Methods: Pathology database was searched for ovarian Endometrioid borderline tumor (EBT) and Seromucinous borderline tumor (SMBT) for a 10-year period (2010-2020). The cohort consisted of 10 EBT (6 of which had focal microinvasion or carcinoma) and 12 SMBT(2 of which had focal carcinoma ). For comparison, 1 borderline Brenner. 15 serous borderline tumors (SBT) and 15 mucinous borderline tumors (MBT) were also included. After reviewing slides, a block with adequate borderline tumor was selected for IHC stains. For the cases with carcinoma, two different blocks with each component were selected. In all selected blocks, IHC stains for four MMRP (MLH1, PMS2, MSH2, MSH6) were performed. The complete absence of nuclear staining in tumor cells was considered as “loss” of the MMRP expression. Any “weak” or “focal” nuclear staining was considered intact. Results: Total 53 cases were evaluated for MMRP IHC. All cases had intact MMRP expression. In cases with carcinoma, both components (BT and carcinoma) have intact MMR IHC expression. See table. Conclusions: Our study did not show loss of MMRP IHC expression in EMT or SMBT. However, our study consisted of a small number of cases. Multi Institutional study with a large number of cases can be helpful in future to further evaluate the role of MMRP IHC in EMT and SMBT. [Table: see text]
Upregulation of HSPB1 heat shock gene and ERCC1 gene on serous ovarian cancer cell line in HIPEC in vitro model.
Authors: Andrade Warne Pedro , Gonçalves Bryan Ôrtero Perez , Silva Luciana Maria , Dasilva Filho Agnaldo Lopes 
Published: June 2021

e17559 Background: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, with the presence of chemoresistance contributing to the poor prognosis. Approximately 80% of cases are diagnosed in stage III C and are treated with cytoreduction surgery followed by adjuvant chemotherapy. However, 70 percent of these patients have pelvic and peritoneal recurrences. Heat Shock Proteins are produced in response to pathophysiological stress and take part in several stages of carcinogenesis, acting primarily as anti-apoptotic agents. They are also implicated in resistance to chemotherapy in several types of tumors. In an attempt to improve oncological results, new therapeutic approaches such as intraperitoneal chemotherapy and HIPEC have been proposed in recent studies with gains in overall survival (OS). However, some questions have not yet been answered. Methods: in the study cultures of ovarian cancer cells were performed TOV-21G (clear cell carcinoma), SK-OV-3 (platinum-resistant serous carcinoma) and OV-90 (high-grade serous). Cell cytotoxicity (MTT) assay was performed. The ovarian cancer cells lines were treated with cisplatin in normothermia (37 degrees Celsius) and cisplatin in hyperthermia (41 degrees Celsius) and a control group treated with PBS saline solution at (37 degrees Celsius and 41 degrees Celsius) for 24 hours followed by new supplementation and a new 3-hours incubation. Clonogenic assay was performed. Then they were submitted to RNA extraction and reverse transcription. qRT-PCR was performed to compare the expression of TRAP1, HSPB1, HSPD1, HSPA1A, HSPA1L and ERCC1 in different treatments. Results: There was no statistical difference in relation to cytotoxicity between treatment with heated cisplatin compared to treatment with normothermia. It was not possible to evaluate the expression of the heat shock genes in the SK-OV3 lineage.The HSPB1, HSPD1, TRAP1 and ERCCC1 genes were positively regulated in OV-90 submitted to hyperthermia in relation to normothermia and there were no significant changes in expression in the TOV-21-G. Conclusions: In conclusion, we suggest that OV-90 Serous ovarian cancer cell line was more susceptibly at hyperthermia by cisplatin. The HSPA1A, HSPA1L, TRAP1 and HSPB1 heat shock genes and ERCC1 genes were upregulated in the heated cisplatin group and contribute to a poor prognosis related to resistance. The HSPB1 and ERCC1 genes had the greatest expression with 1000x higher.Thus, it is necessary to evaluate these genes in a clinical study of HIPEC.
Feasibility of ovarian preservation as a stage in correcting the quality of life in young patients after gynecologic surgeries.
Authors: Chernikova Natalia V. , Verenikina Ekaterina V. , Poryvaev Yuriy A. , Myagkova Tatiana Yu. , Menshenina Anna P. 
Published: June 2021

e17560 Background: The purpose of the study was to analyze the structure and activity of the blood flow in the preserved ovaries after gynecologic surgeries. Methods: We monitored 50 patients (mean age 35.8±0.5 years) using sonography after ovary-sparing hysterectomy for benign, precancerous and preinvasive malignant uterine diseases. For revascularization, the preserved ovaries were attached to the lateral wall of the small pelvis or to the base of round ligaments of the uterus. Results: Ovarian hypertrophy was recorded in 3 women during the first year of the follow-up; the ovaries returned to the initial size without correction by 24 months. By the third year of observation, 94% of women had normal gonadal sizes, and only 2 women had ovarian hypoplasia. During the entire observation period (3 years), in 91% of cases, we could visualize the regular maturation of follicles in the preserved ovaries, which indicated the preservation of ovulatory function. The use of Doppler techniques during 24 months of the follow-up demonstrated that the blood circulation in the attached ovaries after hysterectomy was decreased on the average by 20.3%, compared to the intact ovaries. Conclusions: After the critical period of hysterectomy, the blood flow in the ovaries in almost all patients remains sufficient during the first 2-3 years, stimulating the regular growth of follicles and maintaining the gonadal activity. The quality of life of the operated patients during the first three years of follow-up remains optimal without additional correction with hormone replacement therapy.
Overall survival differences between women and men with leiomyosarcomas.
Authors: Wadhawan Ashna , Khunger Arjun , Samuels Shenae , Niu Jianli , Adames Jorge , Sareli Candice , Raez Luis E. , Salzberg Matthew Philip , Vulfovich Michel , Hussein Atif Mahmoud 
Published: June 2021

e17562 Background: Leiomyosarcomas (LMS) are one of the most frequently occurring subtypes of soft tissue sarcomas and are associated with poor prognosis and high risk of recurrence even in the early stages of the disease. Primary management involves surgical excision followed by chemotherapy for all stages. We sought to determine the prognostic factors on associated with leiomyosarcoma survival. Methods: The National Cancer Database from 2004-2016 was utilized to obtain demographics, tumor characteristics and treatment factors of LMS. LMS was divided into three groups for analysis- women with uterine LMS, women with ex-uterine LMS and men with LMS. Univariate and backward stepwise multivariate logistic regression models were used to determine prognostic factors associated with long-term survival in each group. Kaplan-Meier method with log rank test was used to compare overall survival (OS) rates among the three groups. Results: A total of 23194 patients were identified. Only 18.7% of men with LMS utilized chemotherapy as compared to 47.4% women with uterine and 25.0% with ex-uterine LMS. Both men and women had comparable palliative care use- 3.9% in women with uterine LMS, 3.5% in women with ex-uterine LMS and 3.0% in men with LMS. There were statistically significant differences (P=0.000) between overall survival among the three groups. Median OS was highest among men with LMS (72m) followed by women with ex-uterine LMS (57.2m) and women with uterine LMS (36.7 m). On multivariate analysis, in women with uterine LMS, increasing age (OR =0.95, P=0.018), presence of lymphovascular invasion (OR=0.25, P=0.000) were associated with decrease in the likelihood of survival. In women with ex-uterine LMS, increasing age (OR=0.97, P=0.000), increasing stage (I-IV) (OR=0.56, P=0.000), presence of tumor (OR=0.39, P=0.001), those with residual tumor and surgical margins (OR=0.87, P=0.009), and patients who received systemic therapy and surgery (OR= 0.85, P=.0016) had a reduced likelihood of survival. In men with LMS, factors such as increasing age (OR=0.96, P=0.000), increasing number of regional lymph nodes (OR=0.91, P=0.027), having had a surgical diagnostic or staging procedure (OR= 0.69, P=0.004), increasing stage (OR = 0.64, P=0.005), and residual tumor or margins (OR=-0.76, P=0.013) were associated with reduced likelihood of survival. Results also suggest that increasing year of diagnosis was associated with an increased likelihood of survival (OR=1.51; P=0.000). Conclusions: Women were found to comprise almost two third of the patient population with LMS. Men were found to have longer survival than women with LMS, despite low utilization of chemotherapy. It may be due to poor prognosis of LMS in the female reproductive organs while LMS in the extremities has better prognosis. Future prospective trials should stratify based on sex and in women location.
Prognosis of endometrial cancer depends on intracrine ratio of sex steroids.
Authors: Moiseenko Tatiana I. , Frantsiyants Elena M. , Bandovkina Valeria A. , Adamyan Meri L. , Cheryarina Natalia D. , Ardzha Anna Yu. 
Published: June 2021

e17564 Background: Local imbalance of sex steroids (SS) plays a leading role in the development of gynecologic tumors. The purpose of the study was to investigate the effect of changes in SS and E6 protein levels on the course of endometrial cancer (EC). Methods: 50 patients with EC T1-2N0M0 (histologically - endometrioid adenocarcinoma, AC), aged 53.4±3.2 years, were recruited. Levels of SS and E6 protein were determined by standard ELISA systems in tumor samples. The coefficient of estrogens to the amount of testosterone and progesterone – C = (E1+E2):(T+P4) was calculated. Intact endometrium (IE) obtained in surgical treatment for uterine fibroids was used as the intact tissue. Results: AC patients demonstrated elevated estrone (E1) levels, compared to IE: by 2.2 times in 88% and by 5.9 times in 12% cases (p < 0.05). Levels of estradiol (E2) were similar in AC and IE. Progesterone (P4) levels in 32 patients were 1.5 times lower than in IE, and testosterone (T) 1.5 times higher (p < 0.05). P4 in 18 patients was 3 times lower than in IE, and T – 1.4 times lower in 12 women and 2.2 times lower in 6 women (p < 0.05). The C coefficient increased in 32 patients by 1.3 times (p< 0.05), in 12 patients by 2.7 times, in 6 patients by 8.2 times (p < 0.05). E6 protein was found in tumor tissue of 18 patients with elevated C. 6 of 18 women with C = 24.54±2.4 and E6 = 420±32 ng/g of tissue developed recurrence during 6 months, and 12 patients with C = 8.15±1.2 and E6 = 28±2.1 ng/g of tissue developed recurrence in a period of 6 months to 1 year. Women with C = 4.04±0.39 without E6 oncoprotein in tumor tissue had a relapse-free period for more than 1 year. Conclusions: An analysis of C and E6 oncoprotein in tumor tissues allows identification of high-risk patients and a personalized approach to adequate treatment.
Risk and distribution of venous thromboembolic events during treatment for advanced endometrial cancer.
Authors: Salinaro Julia Rose , Goins Emily , Havrilesky Laura J , Davidson Brittany Anne 
Published: June 2021

e17565 Background: Understanding the incidence and timing of venous thromboembolic (VTE) events among patients receiving treatment for advanced endometrial cancer (EC) may help to inform VTE risk stratification and consideration of thromboprophylaxis. We aimed to describe the rate of VTE at each stage of primary treatment for advanced EC as well as the baseline Khorana Score (KS) distribution in this population. Methods: This was a retrospective cohort study of patients diagnosed with stage IVB EC from January 2001 to July 2020 at a single academic institution. The primary outcome was VTE incidence at each stage of primary treatment (at diagnosis, during neoadjuvant chemotherapy [NACT] if applicable, post-operatively [< 30 days from surgery], or during adjuvant chemotherapy). Subjects who were anticoagulated at EC diagnosis were excluded. Khorana score was calculated according to established parameters (1 point each for gynecologic malignancy, pre-chemotherapy platelet count ≥ 350, hemoglobin < 10 or use of red blood cell growth factors, leukocyte count >11, and BMI ≥ 35). Descriptive statistics were used for analysis. Results: There were 76 patients diagnosed with stage IVB EC, 2 of whom were excluded for anticoagulation at cancer diagnosis. Of the remaining 74 patients, 58 underwent primary surgery (78%) and 16 received NACT (22%). A total of 59 received adjuvant chemotherapy after either primary or interval debulking surgery. The two predominant tumor histologies were serous (48%) and endometrioid (20%).A total of 16 VTE occurred during the primary treatment course (22%), 11 among the cohort receiving primary surgery (19%) and 5 among the cohort receiving NACT (31%). The distribution of VTE by stage of primary treatment is shown in Table. The rate of VTE was highest during adjuvant chemotherapy. There were 62 patients for whom a Khorana score could be calculated either before NACT or adjuvant chemotherapy. The distribution of KS was: 17 (27%) with KS 1 (low risk) and 45 (73%) with KS ≥ 2 (intermediate – high risk). Of the 11 non-postoperative VTE, 3 patients (27%) had KS 1 and 8 (73%) had KS ≥ 2. Conclusions: The incidence of VTE among patients with advanced EC was high regardless of whether treatment was initiated with NACT or primary surgery. The majority of VTE occurred among patients with a high KS, but those with a low KS remained at risk. Thromboprophylaxis among all patients with advanced EC may be warranted, and larger studies are needed to determine the performance of KS as a VTE predictor in advanced EC.[Table: see text]