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Employee engagement is one the most essential component of human resource management. For any organisation to survive and succeed, employee engagement is a must. The current study is based on bibliometric analysis of the existing literature. From the search criteria and article selection, only 207 papers from Scopus database were selected, and all these articles belonged to ABDC journals. The objective of the chapter was to look into the publication trends, top research articles, leading countries who are contributing into this field, as well as looking into the top keywords. In this chapter, thematic mapping and bibliometric coupling were used to provide a better idea about the study. Finally, at the end the research, limitations and endeavours for future research are discussed.

Employee silence among healthcare professionals is a significant issue since it can have a significant effect on an organization's success. Employee silence many prevent development of a solid and trustworthy connection between superiors and subordinates, which leads to higher turnover intentions, poor loyalty, and undesirable organisational behaviour.Every superior is responsible for ensuring that employees feel motivated enough to express their opinions.Also superiors must give special attention to promote the emotional well-being of the staff as poor well-being may act as a roadblock for organizational success. The purpose of this paper is to review the literature on employee silence and emotional well-being in hospital setting.

Purpose: The main purpose of the study is to investigate the relationship between job satisfaction, organizational commitment and intention to stay among the millennials working in IT organizations of North India. Research methodology: The present study has adopted descriptive research design and purposive sampling technique was used to gather data from 396 respondents with the help of a structured questionnaire. The data was analyzed using SPSS and PLS-SEM. Findings: Findings revealed that job satisfaction has a significant impact on organizational commitment (β=0.457, p

The present study intends to explore the impact of social media on organizational performance in the IT sector of Tricity and Delhi NCR region. The data collected from lower and middle level employ...

Cervical clear cell carcinoma (CCC) is an HPV-independent tumor historically associated with in-utero exposure to diethylstilboestrol. With the cessation of diethylstilboestro use, most contemporary cases are sporadic and of uncertain pathogenesis, with no established precursor lesion. Following the detection of 3 incidental "early" (FIGO stage IA1) cervical CCCs, all of which displayed adjacent tubo-endometrial metaplasia, we examined further cases, including resection specimens, of this tumor in an attempt to delineate potential precursors. We identified tubo-endometrial metaplasia in proximity to the tumor in 5 of 5 additional primary cervical CCCs, with some tubo-endometrial glands exhibiting subtle mild cytologic atypia. This observation adds to the sparse existing literature proposing tubo-endometrial metaplasia as a precursor to sporadic cervical CCC, with possible progression via an "atypical" transitional phase to malignancy. We also review the published literature regarding possible precursor lesions of primary cervical CCC.

Mullerian adenosarcoma is a biphasic neoplasm composed of benign or atypical Müllerian epithelium and a malignant mesenchymal component that is usually, but not always, of low grade. Focal architectural or cytologic atypia of the epithelial component resembling atypical hyperplasia may uncommonly be present and foci of adenocarcinoma have been rarely reported. Whether the coexistence of these 2 tumor components is a result of independent primaries (collision tumor), adenocarcinoma arising from the epithelial component of the adenosarcoma, an unusual form of carcinosarcoma or some other mechanism is uncertain. To establish the diagnostic criteria and clinical significance of the coexistence of adenocarcinoma in close association with Müllerian adenosarcoma, we conducted a multi-institutional study of these rare tumors. Twenty-six patients were identified with "mixed" adenosarcoma and adenocarcinoma; they ranged in age from 43 to 87 years (median: 66 y). Tumors occurred in the uterine corpus (n=22), ovary (n=2), and the pelvis (n=2). All but 6 had International Federation of Gynecology and Obstetrics (FIGO) stage I disease. All extrauterine tumors were associated with endometriosis. The tumor size ranged from 2 to 25 cm (median: 7.9 cm). The sarcomatous component was of low grade in 18 and high grade in 8 (the majority demonstrating rhabdomyoblastic differentiation); 9 had stromal overgrowth. Twenty-five carcinomas were endometrioid in type (23 FIGO grade 1; 3 FIGO grade 2) and 1 carcinoma was dedifferentiated with FIGO grade 1 endometrioid adenocarcinoma component; 33% of the uterine neoplasms were associated with adjacent endometrial hyperplasia. Next-generation sequencing in 2 tumors identified similar molecular abnormalities in the sarcomatous and carcinomatous components supporting a clonal relationship. Of 10 patients with available follow-up (median: 18 mo), 8 had no evidence of disease and 2 died of recurrent sarcoma at 7 and 8 months. Endometrioid adenocarcinomas that arise in close spatial association with Müllerian adenosarcoma appear to be clonally related to the sarcoma. Unlike carcinosarcomas, these tumors are usually early stage at presentation. The prognosis appears to be driven by the sarcomatous component. These tumors should be distinguished from carcinosarcomas, dedifferentiated endometrial carcinomas, and corded and hyalinized endometrioid carcinomas.

Ovarian immature teratoma is a rare subtype of germ cell tumour that can be pure or associated with non-teratomatous germ cell tumour elements and is graded based on extent of the immature neuroectodermal component. Immature teratoma (IT) can also be associated with somatic differentiation in the form of sarcoma, carcinoma, or extensive immature neuroectodermal elements and may produce low levels of serum alpha-fetoprotein. Variable interpretation of these issues underlies diagnostic and management dilemmas, resulting in substantial practice differences between paediatric and adult women with IT. The Malignant Germ Cell International Consortium (MaGIC) convened oncologists, surgeons, and pathologists to address the following crucial clinicopathologic issues related to IT: (1) grading of IT, (2) definition and significance of 'microscopic' yolk sac tumour, (3) transformation to a somatic malignancy, and (4) interpretation of serum tumour biomarkers. This review highlights the discussion, conclusions, and suggested next steps from this clinicopathologic conference.

Ovarian cancer is most commonly diagnosed at an advanced stage (3 or 4) and remains the deadliest gynecologic malignancy. When diagnosed at stage 1, a survival rate of greater than 90% has been demonstrated, compared with a 5-year survival rate of 27% and 13% for stage 3 and stage 4 disease, respectively. Despite international efforts to identify robust screening methods and increase early-stage detection, to date no evidence that screening saves lives has been presented. The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is a randomized controlled trial that demonstrated no evidence associated with screening for ovarian cancer and reduction in ovarian cancer-related deaths at primary analysis but requires further follow-up. This secondary analysis of the UKCTOCS randomized controlled trial aimed to provide a follow-up and report on the long-term mortality effects of ovarian cancer screening. The UKCTOCS is a multicenter randomized trial of 202,638 women aged 50 to 74 years assigned to 2 annual screening groups (multimodal screening [MMS] vs ultrasound screening [USS]). Women in the United Kingdom were recruited from 13 National Health Service (NHS) centers and randomized to MMS, USS, or no screening in a 1:1:2 ratio. Annual screening in the MMS group involved serum CA125 measurements used in conjunction with the risk of ovarian cancer (ROCA) calculation to guide follow-up involving either no additional screening, repeat CA125 ROCA in 3 months, or transvaginal USS as a second test. Annual screening in the USS group involved transvaginal ultrasound with follow-up involving either continuation of annual screening, repeat in 3 months, or requiring a scan with a senior ultrasonographer within 6 weeks. The primary study outcome was death due to ovarian cancer or tubal cancer. A total of 202,638 women were randomized between April 2001 and September 2005, with screening concluding in December 2011 and follow-up continuing until June 2020. The final analysis cohort consisted of 202,562 women, 50,625 in the MMS group, 50,623 in the USS group, and 101,314 in the no screening group. Compliance with screening was 81% in the MMS group versus 78% in the USS group, with a median of 8 annual screens per participant. The median follow-up was 16.3 years (interquartile range, 15.1–17.3). A total of 2055 participants were diagnosed with ovarian or tubal cancer. At 9.5 years after screening, there was a 47.2% (95% confidence interval, 19.7–81.1) greater incidence of stage 1 disease and a 24.5% (-41.8 to -2.0) lower incidence of stage IV disease in the MMS group compared with the no screening group. Overall, a 39.2% (95% confidence interval, 16.1–66.9) greater incidence of stage I or II disease and a 10.2% (-21.3 to 2.4) lower incidence of stage III or IV disease was observed in the MMS group compared with the no screening group. At follow-up conclusion, 1206 women had died of ovarian cancer (296/50,625 [0.6%] in the MMS group, 291/50,623 [0.6%] in the USS group, 619/101,314 [0.6%] in the no screening group) with no significant difference between the MMS (P = 0.58) and USS (P = 0.36) groups compared with the no screening group. The results of this large-scale ovarian cancer screening trial demonstrate that, on long-term follow-up, while the screening strategies defined here resulted in a greater likelihood of diagnosing early stage disease, neither MMS nor USS resulted in a significant reduction in deaths from ovarian or tubal cancer.

Primary leiomyosarcoma of the fallopian tube is a very rare neoplasm with descriptions limited to case reports. We present the case of a 46-yr-old woman with a history of renal transplantation in whom a primary leiomyosarcoma of the fallopian tube was identified incidentally following hysterectomy and bilateral salpingectomy undertaken for a uterine fibroid. The tumor demonstrated classic morphological and immunohistochemical features of a leiomyosarcoma. It appeared localized to the fallopian tube and was completely resected. Adjuvant therapy was not given but active surveillance initiated. After 14 mo of follow-up, there was no evidence of disease recurrence. We review cases from the past 20 yr with a focus on management and outcomes. Given the rarity of this disease, continued publication of case reports and the creation of a centralized case registry would be of benefit.

Telecommuting as a substitute to conventional arrangements by which workforces achieve their work purposes during COVID-19 outbreak Telecommuting is the practice of telecommunication expertise to permit personnel to accomplish their work responsibilities distantly, detached from their main place of work consistent with job arrangements It’s a virtuous impression to comprehend the significance, paramount practices and possible wellbeing hazards tangled As organisations around the globe are obligatory to telecommute amidst the COVID-19 pandemic, numerous employees are struggling with the idea of working from home for comprehensive stages of lockdown periods Before 2020, telecommuting for all the employees was viewed as unsociable nightmare Currently, it's the prevailing trend of most organisations This research paper is an attempt to find out the issues, challenges and opportunities of telecommuting in the era of Covid-19

The latest FIGO and TNM (eighth edition) staging systems for ovarian, tubal, and peritoneal neoplasms require primary site assignment as tubal/ovarian/peritoneal, but provide no guidance or criteria. Fewer than 10% of extrauterine high-grade serous carcinoma (HGSC) cases present at low stage (stage I/II). Low-stage cases offer a unique opportunity to understand the pattern of disease early in its evolution prior to wide dissemination and provide valuable evidence for guiding specimen handling and tumor staging. This study aimed to examine disease distribution in low-stage tubo-ovarian HGSC. Anonymized pathology reports of 152 stage I/II extrauterine HGSCs from 6 teaching hospitals were analyzed: group 1 (n=67) comprised cases with complete tubal examination by Sectioning and Extensively Examining the FIMbriated end of the tube (SEE-FIM) and group 2 (n=85) consisted of cases without documentation of both tubes being fully examined by the SEE-FIM or a SEE-FIM-like protocol. The stage, site/pattern of involvement, site/size of largest tumor focus and laterality of tubal and ovarian involvement were recorded. Tubal mucosal involvement was present in 95% of optimally examined cases and many factors influenced detection of tubal disease. Bilateral involvement, suggestive of metastasis, was significantly more frequent in the ovaries (35%) than the tubes (9%) (P

Workplace stress is natural and sometime inventible. It is the existing response of human under difficult environment. In fact, adequate amount of stress keeps a person motivated towards his work. However, high level of stress may cause completely opposite situations for a person. A good leader is who can identify the reason of stress in his employee and can eliminate the reason simultaneously. This research focuses on the level of stress among the employees of ITeS–BPO companies and its connection with the level and background of education of a respondent. ITeS–BPO companies located at Delhi and National Capital Region (NCR) was the population for selecting the sample units. The target population of employees of ITeS–BPO include call-floor executives and operational managers at all levels but excluded back-end support staff from departments like HR and administration ITeS–BPO companies. This paper will help the manager to improve the management to minimize the stress in his organization or workplace. Since the competitive environment, technological advancement, HR Practices, economic development, social development are taking place every day the stress level of employees are increasing respectively. As a result, the employees are faced with the problems like pressure, strain, anxiety, tension, trauma which ultimately leads to decrease in productivity.

The classification of ovarian germ cell tumours has remained unchanged for many years, while there have been considerable changes in the testicular classification. In recent years there has been concern about the overtreatment of clinical stage 1 testicular germ cell tumours with increasing use of surveillance for low-risk disease. We outline here the current classification of germ cell tumours of the ovary with particular regard to treatment and outcome and highlight some areas which may cause confusion, particularly pertaining to immature teratomas and mixed germ cell tumours. We suggest that some minor changes to the classification, evidenced by a recent retrospective series by some of the authors, may lead to less adjuvant chemotherapy for immature teratomas and may obviate the need for the grading of immature teratomas, by aligning with testicular experience in pure post-pubertal teratomas. Adoption of this will require retrospective and prospective re-evaluation, but may avoid long-term patient morbidity.

The study measures the impact of selected HRM practices on organisational commitment among educators' based in Northern region of India. An online questionnaire was designed which was duly answered by 428 respondents of Northern India by applying Partial least squares Structural equation modelling (PLS-SEM) version 2.0. The study revealed that educators' gave highest preference to compensation and rewards (β = 0.409, p

Background: This is a feasibility study to determine whether circulating tumour cells (CTCs) are detectable and suitable for molecular profiling in advanced endometrial cancer (aEC). Method: Between October 2012 and February 2014, 30 patients with aEC had baseline and up to 3 follow-up samples. CTCs and stathmin expression were evaluated using the CellSearch platform. Epithelial cell adhesion molecule (EpCAM) and stathmin immunohistochemistry were performed on FFPE tumour tissue. Results: Eighteen from 30 (60%) patients had detectable CTCs during study [1 CTC (n = 7), 2 (n = 4), 3 (n = 1), 4 (n = 2), 7 (n = 1), 8 (n = 1), 22 (n = 1), 172 (n = 1) in 7.5 ml blood]. Ten from 18 patients had between 50 and 100% of detectable CTCs that were stathmin positive. More CTC-positive than CTC-negative patients had non-endometrioid versus endometrioid histology, tumour size ≥5 versus 0.05, 95% confidence interval 0.7-16.2]. Twenty-one tumour blocks were tested for EpCAM and stathmin immunohistochemistry (IHC). Stathmin tumour immunostaining scores (TIS) on IHC were higher in CTC-positive patients. Conclusion: CTC enumeration and molecular profiling with stathmin on the CellSearch platform is feasible in aEC. Stathmin TIS on IHC, a known prognostic marker in EC, was associated with CTC positivity.

Serous surface papillary borderline ovarian tumors (SSPBOTs) are a rare morphologic variant of serous ovarian tumors that are typically confined to the ovarian surface, while the ovaries themselves tend to appear normal in size and shape. In this report, we describe the findings from five premenopausal women diagnosed with SSPBOTs, in whom ultrasound showed grossly normal ovaries that were partially or wholly covered with irregular solid tumors. In all five cases, histologic examination showed evidence of borderline serous tumors. These findings demonstrate that SSPBOTs can be diagnosed on a preoperative sonographic examination, which could facilitate conservative, fertility-sparing surgery in young women affected by this condition.

IT companies have the probable to become foremost examples of women-friendly employers. There is a shift in the employment of women in IT firms and it is considerably increased over the years. Present study evaluates the impact of Autonomy and empowerment on women employee turnover of IT industries and to determine to what extent empowerment makes women employees to stick with the organization. The main objective of study is to determine the association between sixteen empowerment facets and decision of employees to stay with the organization and to determine the most important facet/dimension of empowerment which affect the women employee's decision to stay with the organization. For the purpose of research data has been collected from 15–25 companies of IT industry. The target geographic location for this study focuses on Gurugram ITes companies in which various factors affecting women employee turnover have been studied. The model explained 35.4 percent (Nagelkerke R square) of the variance in decision and correctly classified 83.1% of the cases. Decision to stay in organization depends on Communication empowerment. Factor analyses technique has revealed that women employees gives high importance to flexibility in working hours and their job should allow proper work life balance.

The growth of the organization is purely dependent upon the performance of the employees working there. Now days the hardest job for the employer of the organization is to get maximum output from the employees. Good performance from employees can be achieved through empowerment. If the employees are given full freedom, authority, powers, decision making rights then output can be seen in the form of high performance. The present study focuses to know the impact of empowerment on performance of faculty members working in private universities of Punjab. The secondary objective is to find out the latest UGC regulations to empower the faculty. The data was collected with the help of structured questionnaire. The reliability and validity is checked by cronbach alpha. The sample size for the present study is 527 faculty members. The statistical package for social sciences (SPSS) tool was used to analyse the gather data. Multiple regression analysis is employed to obtain the results.

Employee's performance is considered to be the main reason behind the overall growth of organization. There are many reasons in the organization that leads to both effectual and futile performance of the individuals. In order to get fruitful results, it is important for the manager to empower employees by giving full freedom, authority, and power so they can perform well in every task. The present study also focuses on finding out the impact of empowerment on performance of faculty in private colleges. The study took place in two colleges i.e. Doaba Group of Colleges and CGC Landran situated in the region of Punjab. A sample of 100 respondents was drawn using simple random sampling method from the targeted population. The data was collected from the faculty members with the help of structured questionnaire. To check the reliability and validity of the data Cronbach alpha method was used. The statistical package for social sciences (SPSS) tool was used in order to process and analyze the data. Various statistical techniques were utilized such as descriptive analysis, regression analysis and t-test to check the results. Hence it is concluded that empowerment acts as a recreational tool in improving the performance of faculty members.

A 13-year-old girl presented with pelvic pain and imaging revealed a large right ovarian cystic mass. Histologic examination showed a malignant myxoid tumor with chicken-wire vasculature characteristic of a myxoid liposarcoma. The morphologic appearances were supported by the presence of the rearrangement of the CHOP gene demonstrated by interphase fluorescent in situ hybridization. There was no evidence that this tumor represented metastatic disease. To the best of our knowledge, primary ovarian myxoid liposarcoma has not been previously reported in the English literature. We present the case and briefly discuss the differential diagnosis.

Introduction: There is paucity of information regarding a late toxic reaction after chemoradiation for locally advanced cervical cancer. We discuss this problem with special consideration to total vaginal necrosis (TVN), an underreported severe late complication of chemoradiation. Methods: The records of 98 cervical cancer patients who received chemoradiation at the Department of Oncology of the University College London Hospital between January 2004 and May 2008 were reviewed. Results: Eight women (8.2%) developed a severe late toxic reaction. From these, 3 patients (3.1% of the entire cohort and 37.5% of the patients with a severe late toxic reaction), who were 44 to 60 years old, developed a TVN 6 to 18 months after completion of chemoradiation. In all the TVN cases, surgical debridement was necessary to alleviate the symptoms. This was followed by an extensive period (up to 24 months) of consolidation. Heavy smoking (P = 0.022) was found to be a significant contributing factor for TVN. Conclusions: Total vaginal necrosis is an underreported but serious late complication after chemoradiation and leads to considerable chronic morbidity. Radiologic examinations and biopsies are required to exclude recurrent disease. Microvascular damage from radiation combined with heavy cigarette smoking is likely to be pivotal etiologic factors in the development of TVN. For radiotherapy-induced late toxic effects to step out of the gray area of oncologic literature, the clinical pictures should be reported in a more detailed manner. It might be a promising approach to work out a toxicity scale that combines the existing objectifiable grading systems with subjective quality-of-life assessments.

Grading cervical intraepithelial neoplasia (CIN) determines clinical management of women after abnormal cytology with potential for overdiagnosis and overtreatment. We studied a novel biomarker of human papillomavirus (HPV) life-cycle completion (panHPVE4), in combination with the minichromosome maintenance (MCM) protein cell-cycle marker and the p16INK4a transformation marker, to improve CIN diagnosis and categorization. Scoring these biomarkers alongside CIN grading by 3 pathologists was performed on 114 cervical specimens with high-risk (HR) HPV. Interobserver agreement for histopathology was moderate (κ=0.43 for CIN1/negative, 0.54 for CIN2/≤CIN1, and 0.36 for CIN3). Agreement was good or excellent for biomarker scoring (E4: κ=0.896; 95% confidence interval [CI]: 0.763-0.969; p16INK4a : κ=0.798; 95% CI: 0.712-0.884; MCM: κ=0.894; 95% CI: NC (this quantity cannot be calculated). Biomarker expression was studied by immunofluorescence and immunohistochemistry and was correlated with 104 final CIN diagnoses after histologic review. All 25 histologically negative specimens were p16INK4a and panHPVE4 negative, although 9 were MCM-positive. There were variable extents of p16INK4a positivity in 11/11 CIN1 and extensive panHPVE4 staining in 9/11. Ten CIN2 lesions expressed panHPVE4 and p16INK4a, and 13 CIN2 expressed only p16INK4a. CIN3 showed extensive p16INK4a positivity with no/minimal panHPVE4 staining. PanHPVE4, unlike MCM, distinguished CIN1 from negative. PanHPVE4 with p16INK4a separated CIN2/3 showing only expression of p16INK4a, indicating transforming HR-HPV E7 expression, from CIN1/2 showing completion of HR-HPV life cycle by E4 expression and variable p16INK4a expression. PanHPVE4 and p16INK4a staining are complementary markers that could provide simple, reliable support for diagnosing CIN. Their value in distinguishing CIN1/2 that supports HR-HPV life-cycle completion (and which might ultimately regress) from purely transforming CIN2/3 needing treatment warrants further research.

High-risk human papillomavirus (HPV) types cause cervical lesions of varying severity, ranging from transient productive infections to high-grade neoplasia. Disease stratification requires the examination of lesional pathology, and possibly also the detection of biomarkers. P16(INK4a) and MCM are established surrogates of high-risk HPV E6/E7 activity, and can be extensively expressed in high-grade lesions. Here we have combined these two cellular biomarkers with detection of the abundant HPV-encoded E4 protein in order to identify both productive and transforming lesions. This approach has allowed us to distinguish true papillomavirus infections from similar pathologies, and has allowed us to divide the heterogeneous CIN2 category into those that are CIN1-like and express E4, and those that more closely resemble nonproductive CIN3. To achieve this, 530 lesional areas were evaluated according to standard pathology criteria and by using a multiple staining approach that allows us to superimpose biomarker patterns either singly or in combination onto an annotated hematoxylin and eosin (H&E) image. Conventional grading of neoplasia was established by review panel, and compared directly with the composite molecular pathology visualized on the same tissue section. The detection of E4 coincided with the onset of vacuolation, becoming abundant in koilocytes as the MCM marker declined and cells lost their defined nuclear margins as visualized by standard H&E staining. Of the dual marker approaches, p16(INK4a) and E4 appeared most promising, with E4 generally identifying areas of low-grade disease even when p16(INK4a) was present. Extensive p16(INK4a) expression usually coincided with an absence of E4 expression or its focal retention in sporadic cells within the lesion. Our results suggest that a straightforward molecular evaluation of HPV life-cycle deregulation in cervical neoplasia may help improve disease stratification, and that this can be achieved using complementary molecular biomarker pairs such as MCM/E4 or, more promisingly, p16(INK4a)/E4 as an adjunct to conventional pathology.

The need to accurately identify tissue of an individual can arise in a variety of settings including mislabelled slides or sample carryover. Reported rates of carryover range from 0.6% to 2.9% of slides depending on the methods of evaluation. Carryover becomes particularity clinically important when malignant tissue is found in an otherwise benign sample. The suspicion of malignancy causes immense psychological stress to the patient and results in additional management costs due to the additional investigations required to rule out malignancy. Proving a negative can be difficult and many cases result in lifelong follow-up for the patient. Molecular techniques such as PCR amplification of simple tandem repeat (STR) sequences can be used to identify tissue and hence its provenance. At University College London Hospital, STR PCR analysis has been used since 2003. Here the authors report their experience with regard to the clinical scenarios, the technique used and the outcomes.

To evaluate the magnetic resonance (MR) imaging appearance of the testes in women with complete androgen insensitivity syndrome (CAIS), including any benign or malignant changes.This was a retrospective review of the testicular MR images and histologic reports from 25 patients with CAIS who chose to retain their testes beyond age 16 years and who were imaged between January 2004 and December 2010. Ethical approval was obtained, and informed consent was obtained from each subject to review the medical records, images, and histologic slides and reports. Imaging and histologic findings were compared.Twelve patients (mean age, 24 years; age range, 18-39 years) retained their testes and 13 (mean age, 22 years; age range, 17-37 years) eventually underwent gonadectomy. Review of the MR images showed that testicular parenchyma was heterogeneous in 30 of 46 testes (65%). The most common changes on MR images included simple-looking paratesticular cysts (34 of 46 testes, 74%) and low-signal-intensity, well-defined Sertoli cell adenomas (26 of 46 testes, 56%). Correlation of the histologic and MR imaging findings showed that MR imaging could correctly depict the presence or absence of Sertoli cell adenomas in 19 of 23 testes (83%). Paratesticular cysts were correctly detected in 22 of 23 testes (96%). Microscopic examination showed that the testes were composed of atrophic seminiferous tubules, whereas germ cells were found in 13 of 26 testes (50%). All paratesticular cysts were confirmed to be benign; however, a focus of intratubular germ cell neoplasia was found in a Sertoli cell adenoma. Premalignant foci were detected in three patients, two with intratubular germ cell neoplasia and one with sex cord tumor with annular tubules. No invasive cancers were found.MR imaging is accurate in the detection of testicular changes, including paratesticular cysts and Sertoli cell adenomas. Although these changes are usually benign, Sertoli adenomas can sometimes harbor premalignant lesions. MR imaging cannot depict premalignant changes; therefore, the standard of care for patients with CAIS should remain gonadectomy after puberty.

TB filled in by Laureen Please see later in the article for the Editors' Summary, Background Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. Methods and Findings Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop precancerous endometrial lesions with increasing age, and these lesions also demonstrated a lack of PTEN expression. Conclusions HAND2 methylation is a common and crucial molecular alteration in endometrial cancer that could potentially be employed as a biomarker for early detection of endometrial cancer and as a predictor of treatment response. The true clinical utility of HAND2 DNA methylation, however, requires further validation in prospective studies. Please see later in the article for the Editors' Summary, Editors' Summary Background Cancer, which is responsible for 13% of global deaths, can develop anywhere in the body, but all cancers are characterized by uncontrolled cell growth and reduced cellular differentiation (the process by which unspecialized cells such as “stem” cells become specialized during development, tissue repair, and normal cell turnover). Genetic alterations—changes in the sequence of nucleotides (DNA's building blocks) in specific genes—are required for this cellular transformation and subsequent cancer development (carcinogenesis). However, recent evidence suggests that epigenetic modifications—reversible, heritable changes in gene function that occur in the absence of nucleotide sequence changes—may also be involved in carcinogenesis. For example, the addition of methyl groups to a set of genes called stem cell polycomb group target genes (PCGTs; polycomb genes control the expression of their target genes by modifying their DNA or associated proteins) is one of the earliest molecular changes in human cancer development, and increasing evidence suggests that hypermethylation of PCGTs is an epigenetic hallmark of cancer. Why Was This Study Done? The methylation of PCGTs, which is triggered by age and by environmental factors that are associated with cancer development, reduces cellular differentiation and leads to the accumulation of undifferentiated cells that are susceptible to cancer development. It is unclear, however, whether epigenetic modifications have a causal role in carcinogenesis. Here, the researchers investigate the involvement of epigenetic factors in the development of endometrial (womb) cancer. The risk of endometrial cancer (which affects nearly 50,000 women annually in the United States) is largely determined by environmental and lifestyle factors. Specifically, the risk of this cancer is increased in women in whom estrogen (a hormone that drives cell proliferation in the endometrium) is functionally dominant over progesterone (a hormone that inhibits endometrial proliferation and causes cell differentiation); obese women and women who have taken estrogen-only hormone replacement therapies fall into this category. Thus, endometrial cancer is an ideal model in which to study whether epigenetic mechanisms underlie carcinogenesis. What Did the Researchers Do and Find? The researchers collected data on genome-wide DNA methylation at cytosine- and guanine-rich sites in endometrial cancers and normal endometrium and integrated this information with the human interactome and transcriptome (all the physical interactions between proteins and all the genes expressed, respectively, in a cell) using an algorithm called Functional Epigenetic Modules (FEM). This analysis identified HAND2 as the hub of the most highly ranked differential methylation hotspot in endometrial cancer. HAND2 is a progesterone-regulated stem cell PCGT. It encodes a transcription factor that is expressed in the endometrial stroma (the connective tissue that lies below the epithelial cells in which most endometrial cancers develop) and that suppresses the production of the growth factors that mediate the growth-inducing effects of estrogen on the endometrial epithelium. The researchers hypothesized, therefore, that epigenetic deregulation of HAND2 could be a key step in endometrial cancer development. In support of this hypothesis, the researchers report that HAND2 methylation was increased in premalignant endometrial lesions (cancer-prone, abnormal-looking tissue) compared to normal endometrium, and was associated with suppression of HAND2 expression. Moreover, a high level of endometrial HAND2 methylation in premalignant lesions predicted a poor response to progesterone treatment (which stops the growth of some endometrial cancers), and analysis of HAND2 methylation in endometrial secretions collected from women with postmenopausal bleeding (a symptom of endometrial cancer) accurately identified individuals with early stage endometrial cancer. Finally, mice in which the Hand2 gene was specifically deleted in the endometrium developed precancerous endometrial lesions with age. What Do These Findings Mean? These and other findings identify HAND2 methylation as a common, key molecular alteration in endometrial cancer. These findings need to be confirmed in more women, and studies are needed to determine the immediate molecular and cellular consequences of HAND2 silencing in endometrial stromal cells. Nevertheless, these results suggest that HAND2 methylation could potentially be used as a biomarker for the early detection of endometrial cancer and for predicting treatment response. More generally, these findings support the idea that methylation of HAND2 (and, by extension, the methylation of other PCGTs) is not a passive epigenetic feature of cancer but is functionally involved in cancer development, and provide a framework for identifying other genes that are epigenetically regulated and functionally important in carcinogenesis. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001551 The US National Cancer Institute provides information on all aspects of cancer and has detailed information about endometrial cancer for patients and professionals (in English and Spanish) The not-for-profit organization American Cancer Society provides information on cancer and how it develops and specific information on endometrial cancer (in several languages) The UK National Health Service Choices website includes an introduction to cancer, a page on endometrial cancer, and a personal story about endometrial cancer The not-for-profit organization Cancer Research UK provides general information about cancer and specific information about endometrial cancer Wikipedia has a page on cancer epigenetics (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) The Eve Appeal charity that supported this research provides useful information on gynecological cancers

DNA methylation of polycomb group target (PCGT) genes is an early step in carcinogenesis and could potentially be assayed to determine cancer risk prediction. To assess whether methylation changes in PCGT genes in normal tissue is able to predict the presence of cancer, we studied HOXA gene methylation in normal endometrium from premenopausal ovarian cancer patients and age-matched healthy controls without ovarian cancer. DNA methylation of HOXA9 and HOXA11 genes in normal endometrium was associated with ovarian cancer in an initial test set and this was subsequently confirmed in independent validation sample sets. The overall risk of ovarian cancer was increased 12.3-fold by high HOXA9 methylation for all stages, and 14.8-fold for early stage ovarian cancers, independent of age, phase of the menstrual cycle and histology of the cancer. The results of this proof of principle study demonstrate the potential to detect ovarian cancer via analysis of normal endometrial cells and provide insight into the possible contribution of this novel approach in ovarian cancer risk prediction and prevention.

Aim: To assess whether: (1) clinical outcomes for ovarian vs. endometrial CS were comparable (2) the epithelial histological subtype or presence of heterologous elements in the mesenchymal component impacted overall survival (OS) (3) a personal or family history (FHx) of cancer was associated with OS. Methods: Women treated at University College London Hospital Gynae-oncology Unit between April 2002 – 2011 were identified using electronic records. Patient clinical data and full histological reports were collected retrospectively from the medical records. Results: 82 patients (72 endometrial; 10 ovarian) with a median age of 67 years were identified. 22% had a prior cancer history and 3.6% had previously received abdominal/pelvic radiotherapy (RT). Median OS was 26.7 months. Analysis for OS according to baseline characteristics OS #events/n HR(95% CI) p-value Original Tumour site Endometrial Ovarian 33/72 6/10 1.0 1.33 (0.56 -3.17) 0.5 FIGO Stage I/II III/IV 10/37 22/33 1.0 3.22 (1.52, 6.82) 0.001 Epithelial type Poorly/un-differentiated Other 15/39 16/31 1.0 1.55 (0.75,3.18) 0.23 Cancer History No Yes 22/56 10/18 1.00 1.23 (0.59, 2.55) 0.58 Cancer FHx No Yes 26/56 7/15 1.00 1.08 (0.47, 2.49) 0.86 All ovarian CS patients had surgical resection (SR), 90% completed 6 cycles of postoperative carboplatin/paclitaxel chemotherapy (CT) with 20% complete responses (CR) and 40% partial responses (PR). 88% of endometrial CS patients were treated with SR, CT +/- RT. The response rates (RR) after CT were 70% CR and 9% PR. Neither the epithelial subtypes, nor the presence of a heterologous component showed statistically significant difference for OS. Conclusions: Clinical outcome for ovarian (12%) vs. endometrial CS were comparable in regards to OS. FIGO stage was the only statistically significant prognostic factor. There was a trend for worse OS in CS with poorly/un- differentiated adenocarcinoma and/or absence of heterologous components although statistically not significant in this cohort. This warrants further clinical evaluation in a larger study. Disclosure: All authors have declared no conflicts of interest.

5600 Background: CTCs are prognostic and predictive markers in many solid tumours. There are no validated biomarkers to assess treatment (tx) response or molecular therapies in aEC. We conducted a ...

p53 overexpression and loss of PTEN expression have been implicated in the pathogenesis of endometrial cancer. Our aim was to correlate expression levels of these proteins with clinicopathological parameters to characterise their utility as biomarkers. Immunohistochemistry was done on 49 cases of formalin fixed paraffin embedded endometrial cancer tissue for p53 and 47 for PTEN expression. For p53 staining the Hue Saturation and Intensity mathematical model was used to evaluate different degrees of positivity of the immunohistochemical stain. The quick score was used for p53 and immunoreactive score for PTEN was done to score immunoreactivity. For PTEN, average percentage of positive cells and intensity was evaluated and the immunoreactive score was calculated. Both these scoring methods incorporated percentage of positive cells and staining intensity. Univariate Cox regression analysis for cause specific survival showed a hazard ratio of 9.2 for p53 overexpression (P Overexpression of P53 has a negative effect on disease specific survival and was associated with poor prognostic features. We did not demonstrate a significant association with clinicopathological features assessed and PTEN expression. However of the 8 patients who relapsed all were PTEN negative and 7 were p53 positive. Dual assessment of p53 and PTEN warrants further investigation as a prognostic indicator. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C32. Citation Format: Bihani Kularatne, Arrigo Capitanio, Rupali Arora, Philippa Jones, Andre Lopes, Jennifer Paterson, Rebecca Kristeleit. PTEN and p53 expression in endometrial cancer correlated with clinicopathological phenotype. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C32.