BRCA awareness and testing experience in the UK Jewish population: a qualitative study.

BACKGROUND: 1 in 40 UK Jewish individuals carry a pathogenic variant in BRCA1/BRCA2. Traditional testing criteria miss half of carriers, and so population genetic testing is being piloted for Jewish people in England. There has been no qualitative research into the factors influencing BRCA awareness and testing experience in this group. This study aimed to explore these and inform improvements for the implementation of population genetic testing. METHODS: Qualitative study of UK Jewish adults who have undergone BRCA testing. We conducted one-to-one semistructured interviews via telephone or video call using a predefined topic guide, until sufficient information power was reached. Interviews were audio-recorded, transcribed verbatim and interpreted using applied thematic analysis. RESULTS: 32 individuals were interviewed (28 carriers, 4 non-carriers). We interpreted five themes intersecting across six time points of the testing pathway: (1) individual differences regarding personal/family history of cancer, demographics and personal attitudes/approach; (2) healthcare professionals' support; (3) pathway access and integration; (4) nature of family/partner relationships; and (5) Jewish community factors. Testing was largely triggered by connecting information to a personal/family history of cancer. No participants reported decision regret, although there was huge variation in satisfaction. Suggestions were given around increasing UK Jewish community awareness, making information and support services personally relevant and proactive case management of carriers. CONCLUSIONS: There is a need to improve UK Jewish community BRCA awareness and to highlight personal relevance of testing for individuals without a personal/family history of cancer. Traditional testing criteria caused multiple issues regarding test access and experience. Carriers want information and support services tailored to their individual circumstances.

Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer.

BACKGROUND: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. METHODS: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. RESULTS: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year's testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. CONCLUSIONS: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

Patient decision aids in mainstreaming genetic testing for women with ovarian cancer: A prospective cohort study.

OBJECTIVE: To evaluate patient preference for short (gist) or detailed/extensive decision aids (DA) for genetic testing at ovarian cancer (OC) diagnosis. DESIGN: Cohort study set within recruitment to the Systematic Genetic Testing for Personalised Ovarian Cancer Therapy (SIGNPOST) study (ISRCTN: 16988857). SETTING: North-East London Cancer Network (NELCN) population. POPULATION/SAMPLE: Women with high-grade non-mucinous epithelial OC. METHODS: A more detailed DA was developed using patient and stakeholder input following the principles/methodology of IPDAS (International Patients Decision Aids Standards). Unselected patients attending oncology clinics evaluated both a pre-existing short and a new long DA version and then underwent mainstreaming genetic testing by a cancer clinician. Appropriate inferential descriptive and regression analyses were undertaken. MAIN OUTCOME MEASURES: Satisfaction, readability, understanding, emotional well-being and preference for long/short DA. RESULTS: The mean age of patients was 66 years (interquartile range 11), and 85% were White British ethnicity. Of the participants, 74% found DAs helpful/useful in decision-making. Women reported higher levels of satisfaction (86% versus 58%, p < 0.001), right amount of information provided (76.79% versus49.12%, p < 0.001) and improved understanding (p < 0.001) with the long DA compared with the short DA. There was no statistically significant difference in emotional outcomes (feeling worried/concerned/reassured/upset) between 'short' and 'long' DA; 74% of patients preferred the long DA and 24% the short DA. Patients undergoing treatment (correlation coefficient (coef) = 0.603; 95% CI 0.165-1.041, p = 0.007), those with recurrence (coef = 0.493; 95% CI 0.065-0.92, p = 0.024) and older women (coef = 0.042; 95% CI 0.017-0.066, p = 0.001) preferred the short DA. Ethnicity did not affect outcomes or overall preference for long/short DA. CONCLUSIONS: A longer DA in OC patients has higher satisfaction without increasing emotional distress. Older women and those undergoing treatment/recurrence prefer less extensive information, whereas those in remission preferred a longer DA.

Changes in the Extracellular Matrix in Endometrial and Cervical Cancer: A Systematic Review.

Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.

Outcomes of Gestational Trophoblastic Disease Management: A Single Centre Review.

Background and Objectives: Gestational trophoblastic disease (GTD) is a group of pregnancy-related malignant and premalignant diseases. The aim of this study was to assess the prognostic value of clinical characteristics to predict treatment outcomes in women with GTD. Materials and Methods: In this retrospective study, 34 patients treated for GTD at the Division of Gynaecology and Perinatology, University Medical Centre Maribor, between 2008 and 2022 were identified. Clinical and pathological characteristics were obtained by analysing patient data records. Results: Within the cohort of 34 patients with GTD, 29 patients (85.3%) had a partial hydatidiform mole (HM) and five patients545 (14.7%) had a complete HM. Two patients with a complete HM developed a postmolar gestational trophoblastic neoplasia (GTN), which represents 5.8% of all cases. Conclusions: GTD is a rare disease that is frequently asymptomatic. The subsequent consequences of GTD, which can lead to malignant transformation, as well life-threatening disease complications, warrant training for early recognition of HMs and timely treatment and surveillance.

Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term secondary lifestyle behavioural outcomes.

OBJECTIVE: Ashkenazi-Jewish (AJ) population-based BRCA testing is acceptable, cost-effective and amplifies primary prevention for breast & ovarian cancer. However, data describing lifestyle impact are lacking. We report long-term results of population-based BRCA testing on lifestyle behaviour and cancer risk perception. DESIGN: Two-arm randomised controlled trials (ISRCTN73338115, GCaPPS): (a) population-screening (PS); (b) family history (FH)/clinical criteria testing. SETTING: North London AJ-population. POPULATION/SAMPLE: AJ women/men >18 years. EXCLUSIONS: prior BRCA testing or first-degree relatives of BRCA-carriers. METHODS: Participants were recruited through self-referral. All participants received informed pre-test genetic counselling. The intervention included genetic testing for three AJ BRCA-mutations: 185delAG(c.68_69delAG), 5382insC(c.5266dupC) and 6174delT(c.5946delT). This was undertaken for all participants in the PS arm and participants fulfilling FH/clinical criteria in the FH arm. Patients filled out customised/validated questionnaires at baseline/1-year/2-year/3-year follow-ups. Generalised linear-mixed models adjusted for covariates and appropriate contrast tests were used for between-group/within-group analysis of lifestyle and behavioural outcomes along with evaluating factors associated with these outcomes. Outcomes are adjusted for multiple testing (Bonferroni method), with P < 0.0039 considered significant. OUTCOME MEASURES: Lifestyle/behavioural outcomes at baseline/1-year/2-year/3-year follow-ups. RESULTS: 1034 participants were randomised to PS (n = 530) or FH (n = 504) arms. No significant difference was identified between PS- and FH-based BRCA testing approaches in terms of dietary fruit/vegetable/meat consumption, vitamin intake, alcohol quantity/ frequency, smoking behaviour (frequency/cessation), physical activity/exercise or routine breast mammogram screening behaviour, with outcomes not affected by BRCA test result. Cancer risk perception decreased with time following BRCA testing, with no difference between FH/PS approaches, and the perception of risk was lowest in BRCA-negative participants. Men consumed fewer fruits/vegetables/vitamins and more meat/alcohol than women (P < 0.001). CONCLUSION: Population-based and FH-based AJ BRCA testing have similar long-term lifestyle impacts on smoking, alcohol, dietary fruit/vegetable/meat/vitamin, exercise, breast screening participation and reduced cancer risk perception.

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases.

Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.

Gynaecological cancers and their cell lines.

Cell lines are widely used for various research purposes including cancer and drug research. Recently, there have been studies that pointed to discrepancies in the literature and usage of cell lines. That is why we have prepared a comprehensive overview of the most common gynaecological cancer cell lines, their literature, a list of currently available cell lines, and new findings compared with the original studies. A literature review was conducted via MEDLINE, PubMed and ScienceDirect for reviews in the last 5 years to identify research and other studies related to gynaecological cancer cell lines. We present an overview of the current literature with reference to the original studies and pointed to certain inconsistencies in the literature. The adherence to culturing rulesets and the international guidelines helps in minimizing replication failure between institutions. Evidence from the latest research suggests that despite certain drawbacks, variations of cancer cell lines can also be useful in regard to a more diverse genomic landscape.

Why is it so difficult to implement a longitudinal clinical reasoning curriculum? A multicenter interview study on the barriers perceived by European health professions educators.

BACKGROUND: Effective clinical reasoning is a core competency of health professionals that is necessary to assure patients' safety. Unfortunately, adoption of longitudinal clinical reasoning curricula is still infrequent. This study explores the barriers that hinder the explicit teaching of clinical reasoning from a new international perspective. METHODS: The context of this study was a European project whose aim is to develop a longitudinal clinical reasoning curriculum. We collected data in semi-structured interviews with responders from several European countries who represent various health professions and have different backgrounds, roles and experience. We performed a qualitative content analysis of the gathered data and constructed a coding frame using a combined deductive/inductive approach. The identified themes were validated by parallel coding and in group discussions among project members. RESULTS: A total of 29 respondents from five European countries participated in the interviews; the majority of them represent medicine and nursing sciences. We grouped the identified barriers into eight general themes: Time, Culture, Motivation, Clinical Reasoning as a Concept, Teaching, Assessment, Infrastructure and Others. Subthemes included issues with discussing errors and providing feedback, awareness of clinical reasoning teaching methods, and tensions between the groups of professionals involved. CONCLUSIONS: This study provides an in-depth analysis of the barriers that hinder the teaching of explicit clinical reasoning. The opinions are presented from the perspective of several European higher education institutions. The identified barriers are complex and should be treated holistically due to the many interconnections between the identified barriers. Progress in implementation is hampered by the presence of reciprocal causal chains that aggravate this situation. Further research could investigate the perceptual differences between health professions regarding the barriers to clinical reasoning. The collected insights on the complexity and diversity of these barriers will help when rolling out a long-term agenda for overcoming the factors that inhibit the implementation of clinical reasoning curricula.

The need for longitudinal clinical reasoning teaching and assessment: Results of an international survey.

Background: Clinical reasoning is a key ability essential for practising health professionals. However, little is known about the current global adoption of clinical reasoning teaching and assessment.Purpose: We aimed to provide insights into how clinical reasoning is deliberately taught and assessed in curricula worldwide and to identify needs and perceived barriers for teaching clinical reasoning to students and educators.Methods: A questionnaire was devised by an international expert group and distributed in a large international medical education community. Data were collected in 2018 and analysed using descriptive statistics. We identified themes in free-text responses using content analysis.Results: Three hundred and thirteen responses from 76 countries were collected. Most respondents were from Europe (34%). While the presence of a longitudinal clinical reasoning curriculum was only reported by 28%, 85% stated that such a curriculum was needed. The lack of awareness of the need to explicitly teach clinical reasoning was the most commonly identified barrier. For assessment, the greatest need identified was for more workplace-based assessment.Conclusions: Global respondents indicate the need to implement explicit longitudinal clinical reasoning curricula. Our findings suggest that efforts should be put into improving faculty development, including evidence-based materials on how to teach and assess clinical reasoning.

Planned home birth in Slovenia-Are we ready?

Nowadays, women want a more intimate and familiar atmosphere during labour, which results in increased planned home birth rates. Every woman has the autonomy to decide where she will give birth; however, it is important that she is informed of risks and advantages beforehand. Home births can be distinguished between planned and unplanned home births. Planned home births can be conducted by professional birth attendants (licensed midwives) or birth assistants (doulas, etc). The rates of Slovenian women who decided to deliver at home are increasing year by year. Researches on home births still present discordant data about home birth safety. Their findings have shown that the main advantage of home birth is a spontaneous birth without medical interventions, especially in multiparous low-risk women. The main disadvantage, however, is a higher risk for neonatal death, in particular on occurrence of complications requiring a transfer to hospital and surgical intervention. Global guidelines emphasize careful selection of candidates suitable for home birth, well-informed pregnant women, education of birth attendants, and strict formation of transfer indications.

Students as partners: Our experience of setting up and working in a student engagement friendly framework.

BACKGROUND: Student engagement (SE) in the curriculum is a positive indicator in the development of students deeply involved in their learning. It also has several benefits for the schools' level of educational innovation and quality assurance. METHOD: In order to identify the most important pearls from the last decade of educational developments within the field of SE at the Faculty of Medicine University of Maribor, we searched through our school's archives, publications and research in the field of medical education. RESULTS: Three areas were identified as the most important SE complements: (i) peer teaching, (ii) school governance, and (iii) extracurricular activities. The paper highlights how many student-driven initiatives move from informal frameworks toward a formal structure, elective courses, and, in the end, compulsory components of the curriculum. DISCUSSION: As demonstrated by the three educational achievements at our school, fostering a high level of SE can lead to innovative curricular changes, benefit the whole school and enable students to deliver highly impactful extracurricular projects.

The passage of fluid into the peritoneal cavity during hysteroscopy in pre-menopausal and post-menopausal patients.

The present study aimed to determine the amount of fluid medium passing through the Fallopian tubes into the peritoneal cavity during a hysteroscopy. This was done to understand the pathophysiology of complications related to the hysteroscopy. Conducted in a general hospital setting, the study examined the fluid inflow-outflow during a hysteroscopy both in pre- and post-menopausal women. A hysteroscopy was performed vaginoscopically for both diagnostic and therapeutic procedures. The study involved 117 patients. 84 (71.8%) of them were pre-menopausal and 33 (28.2%) were classified as post-menopausal. The fluid volume difference in the peritoneal cavity prior to hysteroscopy was 26.0 ± 4.2 mL in the pre-menopausal and 7.7 ± 2.4 mL (p = .001) in the post-menopausal group. The pre-menopausal group's flow rate through the Fallopian tubes was 1.5 ± 0.2 mL/min. In the post-menopausal group, it was 0.4 ± 0.1 mL/min (p < .05). It was found that during the hysteroscopy in the pre-menopausal patients, more fluid flows through the Fallopian tubes and at a higher flow rate. Impact statement What is already known on this subject? The complications during a hysteroscopy (HSC) are usually fluid-related and can result in adverse events such as a fluid overload, the dissemination of malignant cells, or electrolyte misbalance. Currently, there is a poor understanding of how HSC fluid behaviour impacts on the pathophysiology of these adverse procedure effects. What do the results of this study add? There have been no quantitative studies of the behaviour of fluid inside the uterine cavity during HSC, which means a quantification of fluid inflow and absorption is required. Our study adds a quantitative understanding of fluid behaviour during HSC. It shows increased rates of fluid passage, as well as fluid speed, into the peritoneal cavity in pre-menopausal patients. What are the implications of these findings for clinical practice and/or further research? Due to the higher rates of fluid passage and speed in pre-menstrual patients, caution regarding the complications during hysteroscopy and further studies are needed on the impact of different fluid distribution.

Problem-based learning in internal medicine: virtual patients or paper-based problems?

BACKGROUND: Teaching using paper problem-based learning (p-PBL) sessions has left some students fatigued with the learning process. Therefore, attempts have been made to replace p-PBL with digitally enhanced, decision-making PBL in the form of virtual patients (VP). Student enthusiasm for substituting p-PBL with VP has not been quantitatively evaluated on the intended educational effects. AIM: To determine the educational effects of substituting p-PBL sessions with VP on undergraduate medical students in their internal medicine course. METHODS: We conducted a randomised controlled study on 34 third-year undergraduate medical students in the academic year 2015-2016. Student performance after an intervention substituting p-PBL sessions with VP was analysed. The educational outcomes were measured with knowledge exams and the Diagnostic Thinking Inventory. RESULTS: There was no difference in exam performance between groups (P > 0.833) immediately after the intervention, or in long term. Nor was there a significant difference in improvement of diagnostic thinking between groups (P > 0.935 and P > 0.320). CONCLUSIONS: Our study showed no significant improvement in diagnostic thinking abilities or knowledge exam results with the use of VP. Educators can add VP to sessions to motivate students, but a significant improvement to educational outcome should not be expected.

Enhancing primary care clerkships with virtual patients.

BACKGROUND: Virtual patients, computer-assisted patient scenarios, have been used in different medical disciplines over several years. Researchers have already gained knowledge on how it helps foster clinical thinking, fills knowledge gaps and enables patient management. Nonetheless, despite these advances in knowledge, the use of virtual patients in Family Medicine education remains limited. OBJECTIVES: We point out the current knowledge, benefits and potential ways of using virtual patients in the Family Medicine setting. DISCUSSION: Virtual patients can be used as a preparation tool for clinical clerkships as well as learning about patient treatment not usually encountered in every day practice. Regardless of the means of implementation, students benefit from acquiring skills through multifaceted virtual patients. We firmly believe that, when intelligently applied, virtual patients can enhance and improve future Family Medicine education.

What Role do Androgens Play in Endometrial Cancer?

The role of estrogens and progesterone in the development and progression of endometrial cancer is well-established, but there are very little data about the role of androgens. There are five different androgens produced in women: dehydroepiandrosterone sulphate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T) and dihydrotestosterone (DHT). The most potent hormones are T and DHT, the latter being mainly produced from T in peripheral tissues, including endometrium. Although they are considered to exert antiproliferative effects in many settings and the expression of their receptors is more often associated with a good prognosis in EC, it is still unknown in which specific settings androgens have carcinogenic or protective effects in EC.

Ultra-High-Risk Gestational Choriocarcinoma of the Ovary Associated with Ectopic Pregnancy.

Gestational choriocarcinoma of the ovary is an exceptionally rare and highly aggressive tumor. Preoperative diagnosis of extrauterine choriocarcinoma is difficult due to nonspecific clinical presentation and its resemblance to ectopic pregnancy. Without molecular genetic analysis, it is not possible to reliably differentiate gestational from non-gestational choriocarcinoma. Here, we present a case of a 44-year-old woman who presented to our emergency department with complaints of pelvic pain, vaginal bleeding, and amenorrhea. Because of a recent history of conservatively managed ectopic pregnancy, the patient underwent emergency laparoscopy. Right-sided salpingo-oophorectomy was performed due to intraoperatively suspected ovarian ectopic pregnancy. Histopathology results revealed the diagnosis of ovarian choriocarcinoma of possible gestational origin. It was classified as FIGO stage IV and WHO ultra-high-risk, and she underwent multi-agent chemotherapy without major complications. She has remained in complete remission after a 12-month follow-up. Considering the rarity of this diagnosis, we conducted a literature review including all published cases of suspected gestational choriocarcinomas of the ovary. We conclude that due to the rarity of this entity, preoperative differentiating between ovarian ectopic pregnancy and ovarian choriocarcinoma is extremely challenging, and without molecular genetic analysis, it is not possible to identify the genetic origin of the tumor.

Advances in Tumour-Infiltrating Lymphocytes for Triple-Negative Breast Cancer Management.

Triple negative breast cancer (TNBC) is a subtype of breast cancer which does not express or expresses a minimum amount of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) protein. TNBCs include a heterogenic group of cancers that are aggressive, grow rapidly and are associated with poor prognosis and overall survival, mainly attributed to a lack of effective therapeutic targets. For a long time, a major issue with predicting the outcome and prognosis of TNBCs was the lack of an accurate biomarker, a molecule that helps us objectively assess a patient's health status. In recent times, defining the presence of tumor-infiltrating lymphocytes (TIL) is becoming an indispensable method of determining a patient's prognosis. TILs are found in tumor tissue and the surrounding stroma and carry a prognostic value. Furthermore, they are known to improve the effect of systemic therapy. With the rise of immunotherapy, the role of TIL in this newer therapeutic option is a topic of increased importance. The goal behind this research article is a comprehensive review of the current literature on the importance of tumor-infiltrating lymphocytes in the prognosis of TNBC.

The association of Wnt-signalling and EMT markers with clinical characteristics in women with endometrial cancer.

Endometrial cancer is the most common gynecologic malignancy in the developed world. Risk stratification and treatment approaches are changing due to better understanding of tumor biology. Upregulated Wnt signaling plays an important role in cancer initiation and progression with promising potential for development of specific Wnt inhibitor therapy. One of the ways in which Wnt signaling contributes to progression of cancer, is by activating epithelial-to-mesenchymal transition (EMT) in tumor cells, causing the expression of mesenchymal markers, and enabling tumor cells to dissociate and migrate. This study analyzed the expression of Wnt signaling and EMT markers in endometrial cancer. Wnt signaling and EMT markers were significantly correlated with hormone receptors status in EC, but not with other clinico-pathological characteristics. Expression of Wnt antagonist, Dkk1 was significantly different between the ESGO-ESTRO-ESP patient risk assessment categories using integrated molecular risk assessment.

The Role of CTNNB1 in Endometrial Cancer.

Endometrial cancer (EC) is the most common gynaecologic malignancy in the developed countries. Recent evidence suggests that histopathological subtyping together with molecular subgrouping can lead to more accurate assessment of the risk profile for the patient. Clinical studies suggest the currently used molecular classification improves the risk assessment of women with endometrial cancer but does not explain the differences in recurrence profiles clearly. This could be improved by novel markers. One of such are mutations in the ß-catenin (CTNNB1) gene, a frequently mutated gene in endometrial cancer. This shows mutations mostly at phosphorylation sites of the ß-catenin and almost exclusively in the endometrial subgroup of no specific molecular profile. CTNNB1 mutations lead to alterations in the Wnt/ß-catenin signalling pathway, involved in the carcinogenesis and progression of EC by inducing transcription of target genes, whose function is to regulate the cell cycle. Although tumours with mutations in CTNNB1 tend to have low-risk characteristics, they are related to worse outcomes with significantly increased rate of disease recurrence and lower overall survival.