Abstract Objective The study aims at identifying novel markers for circulating tumor cells (CTCs) in patients with epithelial ovarian cancer (EOC), and at evaluating their impact on outcome. Methods ...Microarray analysis comparing matched EOC tissues and peripheral blood leucocytes (N = 35) was performed to identify novel CTC markers. Gene expression of these novel markers and of EpCAM was analyzed using RT-qPCR in blood samples taken from healthy females (N = 39) and from EOC patients (N = 216) before primary treatment and six months after adjuvant chemotherapy. All samples were enriched by density gradient centrifugation. CTC positivity was defined by over-expression of at least one gene as compared to the healthy control group. Results CTC were detected in 24.5% of the baseline and 20.4% of the follow-up samples, of which two thirds were identified by overexpression of the cyclophilin C gene (PPIC), and just a few by EpCAM overexpression. The presence of CTCs at baseline correlated with the presence of ascites, sub-optimal debulking, and elevated CA-125 and HE-4 levels, whereas CTC during follow-up occurred more often in older and platinum resistant patients. PPIC positive CTCs during follow-up were significantly more often detected in the platinum resistant than in the platinum sensitive patient group, and indicated poor outcome independent from classical prognostic parameters. Conclusions Molecular characterization of CTC is superior to a mere CTC enumeration or even be the rationale for CTC diagnostics at all. Ultimately CTC diagnostics may lead to more personalized treatment of EOC, especially in the recurrent situation.
In various cancers, overexpression of cyclooxygenase (COX)-2 and elevated prostaglandin (PG) E2 synthesis have been associated with tumor development and progression. The potential of COX-2 ...inhibitors in cancer prevention and treatment has been shown repeatedly; however, their clinical use is limited due to toxicity. PGE2 signals via EP receptors 1-4, whose functions are analyzed in current research in search for targeted anti-PG therapies. EP2 and EP4 rather promote tumorigenesis, while the role of EP3, especially in breast cancer, is not yet clear and both pro- and anti-tumorigenic effects have been described. Our study evaluates EP3 receptor expression in sporadic breast cancer and its association with clinicopathological parameters, progression-free and overall survival.
Two hundred eighty-nine sporadic breast cancer samples without primary distant metastasis were immunohistochemically analyzed for EP3 receptor expression. Tissue was stained with primary anti-EP3-antibodies. Immunoreactivity was quantified by the immunoreactivity-score (IRS); samples with an IRS ≥ 2 scored as EP3 positive. Chi-squared and Mann-Whitney-U test were used for comparison of data; Kaplan-Meier estimates and Cox-regression were used for survival analyses.
EP3 receptor was expressed in 205 of 289 samples analyzed (70.9%). EP3 receptor expression was not associated with clinicopathological parameters (e. g. tumor size, hormone receptors, lymph node status). Kaplan-Meier estimates showed a significant association of EP3 positivity with improved progression-free survival (p = 0.002) and improved overall survival (p = 0.001) after up to 10 years. Cox regression analysis confirmed EP3 positivity as a significant prognostic factor even when other known prognosticators were accounted for.
In sporadic breast cancer, EP3 receptor expression is not significantly associated with clinicopathological parameters but is a significant prognostic factor for improved progression-free and overall survival. However, the functional aspects of EP3 receptor in breast cancer and the way how EP3 may oppose the pro-tumorigenic effects of PGE2 elevation and COX-2 overexpression are not fully understood so far. Further studies aiming at identification of the factors regulated by EP3 are necessary to evaluate the possibility of targeting EP3 in future anti-tumor therapy in breast cancer.
Propensity scoring (PS) is an established tool to account for measured confounding in non-randomized studies. These methods are sensitive to missing values, which are a common problem in ...observational data. The combination of multiple imputation of missing values and different propensity scoring techniques is addressed in this work. For a sample of lymph node-positive vulvar cancer patients, we re-analyze associations between the application of radiotherapy and disease-related and non-related survival. Inverse-probability-of-treatment-weighting (IPTW) and PS stratification are applied after multiple imputation by chained equation (MICE). Methodological issues are described in detail. Interpretation of the results and methodological limitations are discussed.
The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus ...meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with greater than 90% concordance in the remaining six statements. The high acceptance rate following active deliberation among the GCIG groups confirmed that a consensus process could be applied in a virtual setting. Together with detailed categorisation of unmet needs, these consensus statements will promote the harmonisation of international clinical research in ovarian cancer.
Purpose
Enzymes with epigenetic functions play an essential part in development of cancer. However, the significance of epigenetic changes in cervical carcinoma as a prognostic factor has not been ...fully investigated. Nuclear receptor corepressor (NCoR) presents itself as a potentially important element for epigenetic modification and as a potential prognostic aspect in cervical cancer.
Methods
By immunohistochemical staining of 250 tumor samples, the expression strength of NCoR was measured and evaluated by immunoreactive score (IRS) in the nucleus and cytoplasm.
Results
A low expression of NCoR in our patients was a disadvantage in overall survival. Expression of NCoR was negatively correlated with viral oncoprotein E6, acetylated histone H3 acetyl K9 and FIGO status, and positively correlated to p53.
Conclusions
Our study has identified epigenetic modification of tumor cells thus seems to be of relevance in cervical cancer as well for diagnosis, as a marker or as a potential therapeutic target in patients with advanced cervical carcinoma.
Pelvic inlet area is associated with birth mode Starrach, Teresa; Schmidhuber, Lisa; Elger, Luisa ...
Acta obstetricia et gynecologica Scandinavica,
January 2023, Volume:
102, Issue:
1
Journal Article
Peer reviewed
Open access
Introduction
To determine whether a pelvis is wide enough for spontaneous delivery has long been the subject of obstetric research. A number of variables have been proposed as predictors, all with ...limited accuracy. In this study, we use a novel three‐dimensional (3D) method to measure the female pelvis and assess which pelvic features influence birth mode. We compare the 3D pelvic morphology of women who delivered vaginally, women who had cesarean sections, and nulliparous women. The aim of this study is to identify differences in pelvic morphology between these groups.
Material and methods
This observational study included women aged 50 years and older who underwent a CT scan of the pelvis for any medical indication. We recorded biometric data including height, weight, and age, and obtained the obstetric history. The bony pelvis was extracted from the CT scans and reconstructed in three dimensions. By placing 274 landmarks on each surface model, the pelvises were measured in detail. The pelvic inlet was measured using 32 landmarks. The trial was registered at the German Clinical Trials Register DRKS (DRKS00017690).
Results
For this study, 206 women were screened. Exclusion criteria were foreign material in the bony pelvis, unknown birth mode, and exclusively preterm births. Women who had both a vaginal birth and a cesarean section were excluded from the group comparison. We compared the pelvises of 177 women between three groups divided by obstetric history: vaginal births only (n = 118), cesarean sections only (n = 21), and nulliparous women (n = 38). The inlet area was significantly smaller in the cesarean section group (mean = 126.3 cm2) compared with the vaginal birth group (mean = 134.9 cm2, p = 0.002). The nulliparous women were used as a control group: there was no statistically significant difference in pelvic inlet area between the nulliparous and vaginal birth groups.
Conclusions
By placing 274 landmarks on a pelvis reconstructed in 3D, a very precise measurement of the morphology of the pelvis is possible. We identified a significant difference in pelvic inlet area between women with vaginal delivery and those with cesarean section. A unique feature of this study is the method of measurement of the bony pelvis that goes beyond linear distance measurements as used in previous pelvimetric studies.
Women who delivered by cesarean section have a significantly smaller pelvic inlet area. With this 3D measurement method, not only distances at the pelvic inlet but the complete three‐dimensional pelvic morphology can be recorded.
Background
Estrogen signalling is transmitted via various receptors and multiple intracellular signalling pathways. Estrogen receptor alpha (ERα)-mediated transcription of target genes has been ...demonstrated to be closely linked to human papilloma virus (HPV)-induced carcinogenesis in case of cervical cancer. So far, the role of non-genomic estrogen signals in cervical cancer, e.g. transmitted by the G protein-coupled estrogen receptor (GPER) remains to be rather elusive. Today’s knowledge on the role of GPER in cervical cancer is sparse and—to the best of our knowledge—GPER has not been investigated in context with clinicopathological parameters or prognosis of cervical cancer. Therefore, the current study investigated whether GPER is expressed in cervical cancer tissue. Further, GPER was correlated to clinicopathological parameters, tissue markers of cervical carcinogenesis and to patient overall and recurrence-free survival.
Materials and methods
Cervical cancer tissue was collected from 156 patients during surgery between 1993 and 2002. GPER immunostaining was performed on all the cases and correlated to clinicopathological data. More than half of all patients were diagnosed at advanced stage (FIGO II–IV 93/156; 59.6%) of disease. The large majority of patients presented with tumours of intermediate or high grade (G2–3 140/152, 92.1%). 22 cervical cancer-related deaths (22/156, 14.1%) were documented during the follow-up period.
Results
GPER was detected in various subcellular staining patterns. In 129/156 (82.7%) cases GPER was expressed in the tumour cell cytoplasm (GPER
cyt
). GPER immunopositivity at the cell membrane (GPER
mem
) was found in 114/156 (73.1%) cases. While co-occurrence of both membrane and cytoplasmic staining (GPER
cyt
+ GPER
mem
) was detected in the majority of tissue samples (101/156; 64.7%), only few cases (14/156, 9.0%) were classified as not expressing GPER at all. GPER
cyt
was positively correlated with tumour grade. Statistical associations of GPER and both p16 and p53 were detected. Finally, immunopositivity of GPER
cyt
was predictive for favourable overall as well as recurrence-free survival in cervical cancer of early stage (FIGO I).
Conclusion
This retrospective study reports GPER
cyt
to be associated with improved overall and recurrence-free survival in early-stage cervical cancer. Further investigations are needed thus to determine whether this observation may be of clinical impact. Interestingly, Raloxifene—a GPER-activating selective estrogen receptor modulator—has recently been demonstrated to be preventive for cervical cancer relapse in mice. Whether this effect is only reliant on raloxifene blocking ERα or may also be related to activation of GPER remains to be determined.
Galectins are commonly overexpressed in cancer cells and their expression pattern is often associated with the aggressiveness and metastatic phenotype of the tumor. This study investigates the ...prognostic influence of the expression of galectin7 (Gal-7) and galectin8 (Gal-8) in tumor cell cytoplasm, nucleus and on surrounding immune cells. Primary breast cancer tissue of 235 patients was analyzed for the expression of Gal-7 and Gal-8 and correlated with clinical and pathological data and the outcome. To identify immune cell subpopulations, immunofluorescence double staining was performed. Significant correlations of Gal-7 expression in the cytoplasm with HER2-status, PR status, patient age and grading, and of Gal-8 expression in the cytoplasm with HER2-status and patient age and of both galectins between each other were found. A high Gal7 expression in the cytoplasm was a significant independent prognosticator for an impaired progression free survival (PFS) (
= 0.017) and distant disease-free survival (DDFS) (
= 0.030). Gal-7 was also expressed by tumor-infiltrating macrophages. High Gal-8 expression in the cytoplasm was associated with a significantly improved overall survival (OS) (
= 0.032). Clinical outcome in patients showing both high Gal-7 and with low Gal-8 expression was very poor. Further understanding of the role of galectins in the regulation and interaction of tumor cells and macrophages is essential for finding new therapeutic targets.
During the severe acute respiratory syndrome coronavirus 2 pandemic, several patient groups are at particular risk. Mortality is higher among cancer patients and may be increased further by ...thromboembolic events, which are more common in coronavirus 2019 patients according to recent publications. We discuss the association of gynecologic malignancies, Severe acute respiratory syndrome coronavirus 2, and thromboembolism by reporting a case study and summarizing available literature.
A 71-year-old Caucasian patient with ovarian cancer receiving first-line chemotherapy was diagnosed with deep vein thrombosis and pulmonary embolism. Routine screening revealed infection with severe acute respiratory syndrome coronavirus 2 in absence of specific symptoms. After uneventful recovery, oncologic treatment could be continued a few weeks later.
We performed a systematic review of the literature on PubMed following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The search included articles ahead of print, published between 1 December 2019 and 1 June 2020. Cross-searches were conducted on all relevant articles.
We identified five articles meeting the defined criteria, including two retrospective studies, a review, a position paper, as well as a letter to the editor.
Cancer patients infected with severe acute respiratory syndrome coronavirus 2 have a relatively poor outcome, which may partially be due to a higher rate of thromboembolic events. Thromboprophylaxis is recommended, and scoring systems are helpful in early detection. In cancer patients with severe acute respiratory syndrome coronavirus 2, individual risk for thromboembolic events should be taken into account when considering interruption versus continuation of antitumoral therapy. However, further data and studies are required.
Purpose
The human endometrium consists of different layers (basalis and functionalis) and undergoes different phases throughout the menstrual cycle. In a former paper, our research group was able to ...describe MSX1 as a positive prognosticator in endometrial carcinomas. The aim of this study was to examine the MSX1 expression in healthy endometrial tissue throughout the different phases to gain more insight on the mechanics of MSX-regulation in the female reproductive system.
Materials and methods
In this retrospective study, we investigated a total of 17 normal endometrial tissues (six during proliferative phase and five during early and six during late secretory phase). We used immunohistochemical staining and an immunoreactive score (IRS) to evaluate MSX1 expression. We also investigated correlations with other proteins, that have already been examined in our research group using the same patient collective.
Results
MSX1 is expressed in glandular cells during the proliferative phase and downregulated at early and late secretory phase (
p
= 0.011). Also, a positive correlation between MSX1 and the progesterone-receptor A (PR-A) (correlation coefficient (cc) = 0.0671;
p
= 0.024), and the progesterone receptor B (PR-B) (cc = 0.0691;
p
= 0.018) was found. A trend towards negative correlation was recognized between MSX1 and Inhibin Beta-C-expression in glandular cells (cc = − 0.583;
p
-value = 0.060).
Conclusion
MSX1 is known as a member of the muscle segment homeobox gene family. MSX1 is a p53-interacting protein and overexpression of homeobox MSX1 induced apoptosis of cancer cells. Here we show that MSX1 is expressed especially in the proliferative phase of glandular epithelial tissue of the normal endometrium. The found positive correlation between MSX1 and progesterone receptors A and B confirms the results of a previous study on cancer tissue by our research group. Because MSX1 is known to be downregulated by progesterone, the found correlation of MSX1 and both PR-A and -B may represent a direct regulation of the MSX1 gene by a PR-response element. Here further investigation would be of interest.
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