The REMAR (Rhein-Main-Registry) real-world study: prospective evaluation of the 21-gene breast recurrence score® assay in addition to Ki-67 for adjuvant treatment decisions in early-stage breast cancer.

PURPOSE: Ki-67 is recommended by international/national guidelines for risk stratification in early breast cancer (EBC), particularly for defining "intermediate risk," despite inter-laboratory/inter-observer variability and cutoff uncertainty. We investigated Ki-67 (> 10%- < 40%, determined locally) as a prognostic marker for intermediate/high risk in EBC, pN0-1 patients. METHODS: This prospective, non-interventional, real-world study included females ≥ 18 years, with pN0/pN1mi/pN1, HR+ , HER2-negative EBC, and locally determined Ki-67 ranging 10%-40%. The primary outcome was changes in treatment recommendations after disclosing the Oncotype DX Breast Recurrence Score®(RS) assay result. RESULTS: The analysis included 567 patients (median age, 57 [range, 29-83] years; 70%/1%/29%/ with pN0/pN1mi/pN1 disease; 81% and 19% with RS results 0-25 and 26-100, respectively). The correlations between local and central Ki-67, local Ki-67, and the RS, and central Ki-67 and the RS results were weak (r = 0.35, r = 0.3, and r = 0.46, respectively), and discrepancies were noted in both directions (e.g., local Ki-67 was lower or higher than central Ki-67). After disclosing the RS, treatment recommendations changed for 190 patients (34%). Changes were observed in pN0 and pN1mi/pN1 patients and in patients with centrally determined Ki-67 ≤ 10% and > 10%. Treatment changes were aligned with RS results (adding chemotherapy for patients with higher RS results, omitting it for lower RS results), and their net result was 8% reduction in adjuvant chemotherapy use (from 32% pre-RS results to 24% post-RS results). CONCLUSION: The Oncotype DX® assay is a tool for individualizing treatments that adds to classic treatment decision factors. The RS result and Ki-67 are not interchangeable, and Ki-67, as well as nodal status, should not be used as gatekeepers for testing eligibility, to avoid under and overtreatment.

Endometrial Cancer Lymphadenectomy Trial (ECLAT) (pelvic and para-aortic lymphadenectomy in patients with stage I or II endometrial cancer with high risk of recurrence; AGO-OP.6).

BACKGROUND: The impact of comprehensive pelvic and para-aortic lymphadenectomy on survival in patients with stage I or II endometrial cancer with a high risk of recurrence is not reliably documented. The side effects of this procedure, including lymphedema and lymph cysts, are evident. PRIMARY OBJECTIVE: Evaluation of the effect of comprehensive pelvic and para-aortic lymphadenectomy in the absence of bulky nodes on 5 year overall survival of patients with endometrial cancer (International Federation of Gynecology and Obstetrics (FIGO) stages I and II) and a high risk of recurrence. STUDY HYPOTHESIS: Comprehensive pelvic and para-aortic lymphadenectomy will increase 5 year overall survival from 75% (no lymphadenectomy) to 83%, corresponding to a hazard ratio of 0.65. TRIAL DESIGN: Open label, randomized, controlled trial. In arm A, a total hysterectomy plus bilateral salpingo-oophorectomy is performed. In arm B, in addition, a systematic pelvic and para-aortic lymphadenectomy up to the level of the left renal vein is performed. For all patients, vaginal brachytherapy and adjuvant chemotherapy (carboplatin/paclitaxel) are recommended. MAJOR INCLUSION CRITERIA: Patients with histologically confirmed endometrial cancer stages pT1b-pT2, all histological subtypes, and pT1a endometrioid G3, serous, clear cell, or carcinosarcomas can be included when bulky nodes are absent. When hysterectomy has already been performed (eg, for presumed low risk endometrial cancer), study participation is also possible. EXCLUSION CRITERIA: Patients with pT1a, G1 or 2 of type 1 histology or uterine sarcomas (except for carcinosarcomas), endometrial cancers of FIGO stage III or IV (except for microscopic lymph node metastases) or visual extrauterine disease. PRIMARY ENDPOINT: Overall survival calculated from the date of randomization until death. SAMPLE SIZE: 640 patients will be enrolled in the study. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: At present, 252 patients have been recruited. Based on this, accrual should be completed in 2025. Results should be presented in 2031. TRIAL REGISTRATION: NCT03438474.

The international discussion and the new regulations concerning transvaginal mesh implants in pelvic organ prolapse surgery.

The use of transvaginal mesh implants for POP and urinary incontinence is currently being extensively debated among experts as well as the general public. Regulations surrounding the use of these implants differ depending on the country. Although in the USA, the UK, in Canada, Australia, New Zealand, and France, transvaginal mesh implants have been removed from the market, in most mainland European countries, Asia, and South America, they are still available as a surgical option for POP correction. The aim of this review is to provide an overview of the historical timeline and the current situation worldwide, as well as to critically discuss the implications of the latest developments in urogynecological patient care and the training of doctors.

Pelvic organ prolapse surgery in elderly patients.

PURPOSE: Pelvic organ prolapse (POP) can cause incomplete bladder emptying or hydronephrosis and renal failure. These are serious conditions, especially in elderly women, requiring resolution of POP. Pessary use is an alternative, but there are specific problems or patients may not want it. We therefore conducted a retrospective study on surgical treatment of elderly women with respect to the type of surgery and intra- and postoperative complications. METHODS: From two urogynecologic centers, we reviewed treatment data between 2003 and 2013, including patients ≥80 years of age. From the hospital records, intra- and postoperative data were extracted. RESULTS: 91 cases met the inclusion criteria. Mean age was 84.38 years (±3.05, max 92 years). Two patients (2.2%) were diagnosed with hydronephrosis and two with urosepsis/renal failure. The mean length of surgery was 81 min (±45 min, range 10-270), 94.5% of patients were under general anesthesia. Two bowel lesions occurred. The mean length of hospital stay was 8 days (range 1-22, n = 90). There were no perioperative mortalities. Six patients (6.6%) were admitted to intensive care unit. CONCLUSIONS: In the future, we will be facing a growing number of elderly women seeking care for POP. In our retrospective analysis, we were able to show that POP surgery could be performed safely. We therefore consider surgical treatment as a valuable alternative if pessary use is not an option.

Functional outcome after pelvic floor reconstructive surgery with or without concomitant hysterectomy.

PURPOSE: When counseling patients about surgical alternatives for pelvic organ prolapse (POP) repair, numerous things have to be considered. Uterine preservation vs. hysterectomy is one relevant issue. Hysterectomy has been traditionally performed for POP, but its benefit regarding outcome has never been proven. Furthermore, a growing number of women ask for uterine preservation. METHODS: In this retrospective cohort study, 384 patients who had undergone surgery for POP between 2000 and 2012 at Freiburg University Medical Center were included. Using a standardized questionnaire, further surgeries, urinary incontinence, recurrent POP, pessary use, and satisfaction with the surgical outcome were evaluated. The functional results after uterine preservation vs. concomitant hysterectomy were compared using t test. RESULTS: 196 (51.04%) women were available for follow-up and agreed to participate (n = 122 with hysterectomy, n = 72 with uterine-preserving surgery, respectively). After a mean follow-up time of 67 months, vaginal bulge symptoms and urinary incontinence did not differ between treatment groups. We observed higher success rates and satisfaction scores in the uterine-preserving group. Regarding satisfaction with surgery and whether the patients thought it had been successful, we observed a trend toward better results in the uterine-preserving group (mean satisfaction score: 8.45 ± 2.15 vs. 7.76 ± 2.91, range 0-10, p = 0.061; success: 91.4 vs. 81.7 %, p = 0.087). CONCLUSIONS: There was no difference with regard to functional outcome between patients with or without concomitant hysterectomy. Satisfaction with the operation was slightly higher after uterus preserving surgery. Therefore, uterine-preserving surgery is a valuable option unless there are contraindications.

Neurovascular coupling in pregnancy and the risk of preeclampsia.

BACKGROUND AND PURPOSE: This study investigated whether a short testing of neurovascular coupling during midterm pregnancy could identify women at risk for subsequent preeclampsia. METHODS: Transcranial Doppler sonography of the posterior cerebral artery during a brief visual stimulation was analyzed in 68 women at midterm pregnancy, the primary clinical end point was preeclampsia. RESULTS: Women with bilateral notching of the uterine arteries showed an exaggerated visually evoked blood flow increase and longer time-to-peak. Neurovascular coupling was not significantly associated with the occurrence of preeclampsia. CONCLUSIONS: Neurovascular coupling was altered in women with impaired uteroplacentar vasoregulation but not a significant predictor of preeclampsia.

Comparative analysis of pelvic ligaments: a biomechanics study.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) affects one third of women of all ages and is a major concern for gynecological surgeons. In pelvic reconstructive surgery, native ligaments are widely used as a corrective support, while their biomechanical properties are unknown. We hypothesized differences in the strength of various pelvic ligaments and therefore, aimed to evaluate and compare their biomechanical properties. MATERIALS AND METHODS: Samples from the left and right broad, round, and uterosacral ligaments from 13 fresh female cadavers without pelvic organ prolapse were collected. Uniaxial tension tests at a constant rate of deformation were performed and stress-strain curves were obtained. RESULTS: We observed a non-linear stress-strain relationship and a hyperelastic mechanical behavior of the tissues. The uterosacral ligaments were the most rigid whether at low or high deformation, while the round ligament was more rigid than the broad ligament. CONCLUSION: Pelvic ligaments differ in their biomechanical properties and there is fairly good evidence that the uterosacral ligaments play an important role in the maintenance of pelvic support from a biomechanical point of view.

Effects of intermittent fasting on quality of life tolerance of chemotherapy in patients with gynecological cancers: study protocol of a randomized-controlled multi-center trial.

Fatigue is a very common side effect during intravenous chemotherapy. Unfortunately, only few effective therapeutic options are available, mostly based on daily activity. In our pilot trial we were able to demonstrate that intermittent fasting can reduce fatigue in healthy people, thus we aimed to assess the effects of the fasting dietary on quality of life during chemotherapy in patients with gynecological cancer, especially on the domain of fatigue. The IFAST trial is designed as a prospective, randomized-controlled, multi-center trial. Participation will be offered to women with gynecological cancers (breast cancer, ovarian cancer including peritoneal and fallopian tube cancers, endometrial cancer and cervical cancer) who are planned to receive intravenous chemotherapy for at least three months. Eligible patients will be randomized 1:1, stratified by tumor type and study center. Primary endpoint is the difference in mean change in fatigue, assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT- FS©). Exploratory secondary endpoints will include general Quality of Life impairment, tolerance of chemotherapy, immunological changes, peripheral cell damage in blood cells, as well as tumor response to chemotherapy. There is new evidence that prolonged fasting periods of 46-96 hours during chemotherapy can positively influence the quality of life during chemotherapy. However, these fasting regiments are not feasible for many patients. Intermittent fasting could be a feasible (manageable) option for many patients to actively improve their quality of life and tolerance to chemotherapy and possibly even enhance the effectiveness of chemotherapy. Trial Registration: https://drks.de, identifier DRKS00031429.

Management of Third and Fourth-Degree Perineal Tears After Vaginal Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/079, December 2020).

Purpose This guideline provides recommendations for the diagnosis, treatment and follow-up care of 3rd and 4th degree perineal tears which occur during vaginal birth. The aim is to improve the management of 3rd and 4th degree perineal tears and reduce the immediate and long-term damage. The guideline is intended for midwives, obstetricians and physicians involved in caring for high-grade perineal tears. Methods A selective search of the literature was carried out. Consensus about the recommendations and statements was achieved as part of a structured process during a consensus conference with neutral moderation. Recommendations After every vaginal birth, a careful inspection and/or palpation by the obstetrician and/or the midwife must be carried out to exclude a 3rd or 4th degree perineal tear. Vaginal and anorectal palpation is essential to assess the extent of birth trauma. The surgical team must also include a specialist physician with the appropriate expertise (preferably an obstetrician or a gynecologist or a specialist for coloproctology) who must be on call. In exceptional cases, treatment may also be delayed for up to 12 hours postpartum to ensure that a specialist is available to treat the individual layers affected by trauma. As neither the end-to-end technique nor the overlapping technique have been found to offer better results for the management of tears of the external anal sphincter, the surgeon must use the method with which he/she is most familiar. Creation of a bowel stoma during primary management of a perineal tear is not indicated. Daily cleaning of the area under running water is recommended, particularly after bowel movements. Cleaning may be carried out either by rinsing or alternate cold and warm water douches. Therapy should also include the postoperative use of laxatives over a period of at least 2 weeks. The patient must be informed about the impact of the injury on subsequent births as well as the possibility of anal incontinence.

Diagnosis and Therapy of Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No. 015/091, January 2022): Part 2 with Recommendations on Interventional/Surgical Therapy of Overactive Bladder, Surgical Treatment of Stress Urinary Incontinence and Diagnosis and Therapy of Iatrogenic Urogenital Fistula.

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the surgical treatment of female patients with stress urinary incontinence and urge incontinence. Specific solutions for the diagnostic workup and treatment of uncomplicated and complicated urinary incontinence are discussed. The diagnostics and surgical treatment of iatrogenic urogenital fistula are presented.

Diagnosis and Therapy of Female Urinary Incontinence. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/091, January 2022): Part 1 with Recommendations on Diagnostics and Conservative and Medical Treatment.

Aim This completely revised interdisciplinary S2k-guideline on the diagnosis, therapy, and follow-up care of female patients with urinary incontinence (AWMF registry number: 015-091) was published in December 2021. This guideline combines and summarizes earlier guidelines such as "Female stress urinary incontinence," "Female urge incontinence" and "Use of Ultrasonography in Urogynecological Diagnostics" for the first time. The guideline was coordinated by the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG) and the Working Group for Urogynecology and Plastic Pelvic Floor Reconstruction (Arbeitsgemeinschaft für Urogynäkologie und plastische Beckenbodenrekonstruktion e. V., AGUB). Methods This S2k-guideline was developed using a structured consensus process involving representative members from different medical specialties and was commissioned by the Guidelines Commission of the DGGG, OEGGG and SGGG. The guideline is based on the current version of the guideline "Urinary Incontinence in Adults" published by the European Association of Urology (EAU). Country-specific items associated with the respective healthcare systems in Germany, Austria and Switzerland were also incorporated. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, etiology, classification, symptoms, diagnostics, and treatment of female patients with urinary incontinence. Specific solutions for the diagnostic workup and appropriate conservative and medical therapies for uncomplicated and complication urinary incontinence are discussed.

Prevalence and outcome of urinary retention after laparoscopic surgery for severe endometriosis--does histology provide answers?

INTRODUCTION AND HYPOTHESIS: Urinary retention after radical laparoscopic surgery for severe endometriosis is a clinically relevant complication. We hypothesized a relationship between the amount of resected nerves and the occurrence of urinary retention. METHODS: We evaluated, retrospectively, a cohort of 221 patients. The expression of nerves in the resected specimens was investigated in patients with urinary retention and matched controls using standardized immunohistochemistry techniques. RESULTS: The prevalence of urinary retention was 4.6% (n = 10). Importantly, there was no difference between cases and controls regarding the quantity of nerves in the resected specimens. The cumulative probability of 50% to overcome urinary retention was reached after 5.6 months. Age was the main risk factor for persistent retention (40.3 years with vs. 31.6 years without, p = 0.01). CONCLUSIONS: In older endometriosis patients, surgical radicality should be balanced against preservation of organ function. There is a fairly good chance to recover, even after 6 months, which is important for patient counseling.

Twenty years of laparoscopic sacrocolpopexy: where are we now?

INTRODUCTION AND HYPOTHESIS: Laparoscopic sacrocolpopexy (LSC) was first described almost 20 years ago. This technique aims to provide the outcomes of the gold standard abdominal approach while offering the benefits of minimally invasive surgery. However, the widespread diffusion of LSC in the management of pelvic organ prolapse (POP) is hampered by its presumed length and technical difficulties due to the inherent need for laparoscopic suturing skills. METHODS: In this article, we highlight the current status of LSC based on a historical overview and in the paradigm of an interrelationship between the three different approaches to POP correction. RESULTS: The enormous changes over the past 15 years have contributed to a better understanding of the pathologies and their treatment, which has enabled us to refine LSC, to simplify it, and to make it much more reproducible. CONCLUSIONS: In the future, we will need more prospective studies to compare LSC with vaginal reconstructive surgery.

Vagina, abdominal skin, and aponeurosis: do they have similar biomechanical properties?

INTRODUCTION AND HYPOTHESIS: despite minimal fundamental works, there is an increasing use of meshes in urogynecology. The concept is mainly based on experiences with abdominal wall surgery. We aimed to compare the biomechanical properties of vaginal tissue, abdominal aponeurosis, and skin. METHODS: samples from 11 fresh women cadavers without prolapse were collected. Uniaxial tension tests were performed and stress-strain curves were obtained. RESULTS: biomechanical properties of the vagina, aponeurosis, and skin differed significantly. The aponeurosis was much more rigid and less extendible than the vagina and skin. Vaginal tissue was less rigid but more extendible than skin. There was no difference between the vagina and skin at low strains (p = 0.341), but a highly significant difference at large strains (p = 0.005). CONCLUSIONS: skin and aponeurosis are not suited to predict vaginal tissue biomechanics. We should be cautious when transferring experiences from abdominal wall surgery to vaginal reconstructive surgery.

Internal hernia after laparoscopic sacrocervicopexy.

Whether the peritoneum covering the mesh used in laparoscopic procedures to treat pelvic organ prolapse needs to be sutured is controversial. Herein is reported a case of small bowel obstruction through the mesh, which was sutured at the level of the sacral promontory. The objective of this case report was to emphasize the importance of peritonization, or "burial," of the mesh during these laparoscopic procedures to avert bowel herniation. Furthermore, the need is stressed for a low operative threshold in patients who have undergone such laparoscopic procedures and who demonstrate symptoms of acute abdomen.

Prolapse surgery in women of 80 years and older using the Prolift™ technique.

INTRODUCTION AND HYPOTHESIS: Treatment of genital prolapse in very elderly women is challenging. Although pessary therapy and colpocleisis are effective, they also have drawbacks. There is only scarce literature about surgical therapy in this age cohort, particularly regarding the use of meshes. METHODS: We aimed to evaluate the feasibility, intraoperative complications, and short-term follow-up results of the Prolift™ technique in 62 women aged over 80 years. Mean follow-up time was 6.2 months. RESULTS: Prolift™ implantation was well tolerated by patients with regard to surgery and anesthesia, and hospitalization was relatively short (mean, 3.9 days). Intraoperative complications occurred in 1.6%. Early postoperative complications included increased post-void residual volume (25.8%), urinary tract infection (3.2%), and moderate or severe pain (17.7%). Five patients (8.3%) developed prolapse recurrence, and mesh retraction was observed in six patients (10%). There was no mesh erosion at short-term follow-up. CONCLUSIONS: Treatment of advanced prolapse using Prolift™ in very elderly women is a feasible, safe, and effective surgical option, preserving a functional vagina. Thus, this may represent one alternative to colpocleisis.

Metformin versus acarbose therapy in patients with polycystic ovary syndrome (PCOS): a prospective randomised double-blind study.

The objective of this study was to investigate the effect of metformin versus acarbose in terms of ovulation rate, their impact on hormonal and metabolic status and tolerability of both drugs in patients with polycystic ovary syndrome (PCOS). Seventy-five patients with PCOS were included in this prospective randomised controlled double-blinded clinical study. According to randomisation, patients were allocated to receive either metformin 2550 mg/day (n = 37) or acarbose 300 mg/day (n = 38) for 12 weeks. Primary study outcomes were ovulation rate, restoration of a regular menstrual cycle and the incidence of side effects. Secondary outcomes included treatment-related hormonal and metabolic changes. Comparable high rates of regular menstrual cycles as well as ovulation could be achieved in both groups (70% and 73% for metformin vs. 78% and 59% for acarbose, p = 0.330 and p = 0.185, respectively). In contrast, only in patients treated with metformin a statistically significant decrease in fasting insulin and cholesterol levels as well as BMI was observed. However, comparing both groups at the end of treatment, no significant differences in metabolic and/or hormonal parameters could be detected. Regarding side effects, the rate of flatulence and/or diarrhoea was significantly lower for acarbose compared to metformin (38% vs. 80%, p < 0.001).

Expression of focal adhesion kinase in patients with endometrial cancer: a clinicopathologic study.

INTRODUCTION: The pp125 focal adhesion kinase (FAK) plays a pivotal role in tumor cell signaling. Focal adhesion kinase expression has been linked to tumor cell proliferation, invasion, and metastasis, but data on endometrial cancer are inconclusive. METHODS: We assess FAK expression by immunohistochemistry in endometrial cancer for its value to predict patient prognosis. RESULTS: Of 134 endometrial cancer cases, 120 (89%) revealed moderate and strong expressions of FAK, whereas weak expression was found in 14 (11%) tumors. Kaplan-Meier analysis indicated a clear trend toward improved survival rates for patients with endometrial carcinomas weakly expressing FAK, and notably, there was neither lymph node metastasis nor tumor-related death in this patient subgroup. Increased expression of FAK correlated with higher histological tumor grade (P = 0.002), lymphatic vascular space invasion (P = 0.003), and vascular space invasion (P = 0.02). Significant prognostic survival variables were tumor stage (P < 0.01), histological type (P < 0.01), tumor grade (P = 0.028), and pelvic lymph node status (P = 0.035). Multivariate Cox regression analysis identified histological tumor grade as a significant independent predictor of patient survival (hazards ratio, 2.71; P = 0.03). CONCLUSIONS: Further studies are warranted to elucidate whether FAK expression analysis is a suitable tool in stratifying patients at different risks of disease progress, and wether FAK might become a new molecular target for endometrial anticancer therapy.

Significance of nuclear hTra2-beta1 expression in cervical cancer.

OBJECTIVE: Human Tra2-beta1, a member of the serine/arginine-rich splicing factors, is involved in C/A-dependent mRNA processing and regulation of gene expression. Since several genes involved in cervical carcinogenesis are alternatively spliced and contain C/A rich elements, we aimed to analyze hTra2-beta1 expression and subcellular localization in tumor tissue of women with cervical cancer and to determine its clinical significance. DESIGN: Retrospective study. SETTING: Tertiary-care academic medical center. SAMPLE: One hundred and five patients with cervical cancer and a mean follow up time of 73.1 months. METHODS: Immunohistochemistry of paraffin-embedded tissues was performed and hTra2-beta1 expression was correlated with clinico-pathological variables including patient outcome. RESULTS: Cytoplasmic hTra2-beta1 protein expression was found in 20% of cases, while all tumors revealed nuclear immunoreactivity with strong expression in 54.3% of cases. There was a significant inverse correlation between nuclear and cytoplasmic protein expression, suggesting a potentially relevant shuttle process of hTra2-beta1 between both cellular compartments. Patients with weak expressing hTra2-beta1 tumors showed an improved survival with a tumor-related death rate of 8.3% compared to 23.7% in patients with moderate and high intranuclear hTra2-beta1 expression, respectively. CONCLUSIONS: Our data support the hypothesis of a biological relevance for hTra2-beta1 expression in cervical cancer. The observed shuttle process of this splicing factor with higher concentrations in the nucleus should have pronounced effects on the cellular function and tumor biology of the affected tumors, leading to the worse patient outcome.

Alpha-folate receptor expression in epithelial ovarian carcinoma and non-neoplastic ovarian tissue.

BACKGROUND: The goal of this study was to evaluate the expression pattern and intracellular localization of alpha-folate receptor (alpha-FR) protein in human ovarian carcinoma compared with non-neoplastic ovarian tissue. MATERIALS AND METHODS: Using immunohistochemistry (IHC), alpha-FR protein expression was analyzed in specimens of 104 human ovarian carcinomas and 30 non-neoplastic ovaries. RESULTS: In 97% of the ovarian carcinomas, clear alpha-FR protein expression was detected (14% weak, 39% moderate, 44% strong). In the non-neoplastic ovaries, no (37%) or only weak (63%) expression was observed (p<0.0001). The tumor cells were characterized by a diffuse and homogeneous staining pattern. In tumor and non-tumor tissue, alpha-FR protein was detected predominantly in the cellular cytoplasm. In 41% of the ovarian carcinomas, cytoplasmic expression was localized towards the outer boarders of the invasive tumor cells and 30% exhibited additional nuclear alpha-FR protein expression. CONCLUSION: Compared with nonneoplastic ovaries, alpha-FR protein is overexpressed in human ovarian carcinoma tissue.