Identification and subsequent validation of transcriptomic signature associated with metabolic status in endometrial cancer.

Aberrant metabolism has been identified as a main driver of cancer. Profiling of metabolism-related pathways in cancer furthers the understanding of tumor plasticity and identification of potential metabolic vulnerabilities. In this prospective controlled study, we established transcriptomic profiles of metabolism-related pathways in endometrial cancer (EC) using a novel method, NanoString nCounter Technology. Fifty-seven ECs and 30 normal endometrial specimens were studied using the NanoString Metabolic Panel, further validated by qRT-PCR with a very high similarity. Statistical analyses were by GraphPad PRISM and Weka software. The analysis identified 11 deregulated genes (FDR ≤ 0.05; |FC|≥ 1.5) in EC: SLC7A11; SLC7A5; RUNX1; LAMA4; COL6A3; PDK1; CCNA1; ENO1; PKM; NR2F1; and NAALAD2. Gene ontology showed direct association of these genes with 'central carbon metabolism (CCM) in cancer'. Thus, 'CCM in cancer' appears to create one of the main metabolic axes in EC. Further, transcriptomic data were functionally validated with drug repurposing on three EC cell lines, with several drug candidates suggested. These results lay the foundation for personalized therapeutic strategies in this cancer. Metabolic plasticity represents a promising diagnostic and therapeutic option in EC.

Fertility-Sparing Methods in Adolescents Affected by Endometrial Cancer: A Comprehensive Review.

Although in developed countries endometrial cancer (EC) is the most common gynecological malignancy, its occurrence in adolescents is exceedingly rare. The increasing rate of obesity in children and adolescents is held responsible for the increasing prevalence of EC in younger cohorts of patients. The diagnosis of this malignancy can have devastating consequences for future fertility because standard treatment protocols for EC include hysterectomy. Here, we present the first detailed review of the world literature on EC in subjects aged 21 years or younger (n = 19). The mean age at diagnosis was 16.7 ± 0.6 years. One patient (5.3%) had a Type II (high-risk) disease. No communication retrieved from the search reported on patient death; however, two (10.5%) patients were lost to follow-up. There was also a high proportion (five subjects, or 26.3%) of cases with genetic background (Cowden syndrome and Turner syndrome), therefore genetic screening or a direct genetic study should be considered in very young patients with EC. The current fertility-sparing options, limited to Type I (low-risk) disease, are presented and discussed. Such information, obtained from studies on older women, translates well to adolescent girls and very young women. Careful anatomopathological monitoring at follow-up is essential for the safety of a conservative approach. Improved survival in very young EC patients makes the preservation of fertility a central survivorship issue, therefore both patients and caregivers should undergo counseling regarding available options. Moreover, our study suggests that genetic syndromes other than Lynch syndrome may be associated with EC more frequently than previously thought.

Myometrial Responses to Beta-Adrenoceptor Antagonists in Gynecological Malignancies.

OBJECTIVE: The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. DESIGN: This was a controlled and prospective ex vivo study. SETTING: The work was conducted as a collaboration between 4 academic departments. MATERIALS AND METHODS: Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; N = 15), and ovarian (N = 15), endometrial (N = 15), synchronous ovarian-endometrial (N = 3), and cervical cancer (N = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. RESULTS: Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all p < 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both p < 0.001). LIMITATIONS: These results require now to be placed into a firm clinical context. CONCLUSIONS: Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.

Insulin Resistance and Endometrial Cancer: Emerging Role for microRNA.

Endometrial cancer (EC) remains one of the most common cancers of the female reproductive system. Epidemiological and clinical data implicate insulin resistance (IR) and its accompanying hyperinsulinemia as key factors in the development of EC. MicroRNAs (miRNAs) are short molecules of non-coding endogenous RNA that function as post-transcriptional regulators. Accumulating evidence has shown that the miRNA expression pattern is also likely to be associated with EC risk factors. The aim of this work was the verification of the relationships between IR, EC, and miRNA, and, as based on the literature data, elucidation of miRNA's potential utility for EC prevention in IR patients. The pathways affected in IR relate to the insulin receptors, insulin-like growth factors and their receptors, insulin-like growth factor binding proteins, sex hormone-binding globulin, and estrogens. Herein, we present and discuss arguments for miRNAs as a plausible molecular link between IR and EC development. Specifically, our careful literature search indicated that dysregulation of at least 13 miRNAs has been ascribed to both conditions. We conclude that there is a reasonable possibility for miRNAs to become a predictive factor of future EC in IR patients.

Ovarian endometrioma - a possible finding in adolescent girls and young women: a mini-review.

Young girls before menarche or menstruating adolescent women may experience long-term drug-resistant chronic pelvic pain, as well as other symptoms associated with pelvic mass. In such cases, it is of great importance to consider ovarian endometrioma in the differential diagnosis. In general, endometrioma is recognized as an ovarian cyst. However, in most cases, the pathology represents pseudocyst with a partial or complete endometrial-like lining with extraovarian adhesions and endometriotic implants which are likely to occur at the sites of ovarian adhesions and at the ceiling of the ovarian fossa. Ovarian endometriomas occur in 17-44% patients with endometriosis and account for 35% of all benign ovarian cysts. The time span from the onset of menarche to the time of endometrioma formation, which requires surgical intervention, has been evaluated to be a minimum of 4 years. The pathogenesis of early-life endometrioma may be different from other types of endometriosis. Diagnosis is often delayed, especially in adolescents, who tend to wait too long before seeking professional help. The three specific aims of treatment in adolescents with endometriosis and endometriomas are control of symptoms, prevention of further progression of the disease as well as preservation of fertility. Increasing evidence demonstrates association between ovarian endometriosis and ovarian cancer. In the present mini-review, we draw the particular attention of clinicians to such a possibility, even if relatively infrequently reported.

The effects of extended nitric oxide release on responses of the human non-pregnant myometrium to endothelin-1 or vasopressin.

BACKGROUND: Uterotonic mediators: endothelin-1 (ET-1), arginine vasopressin (AVP), and nitric oxide (NO) play important roles in the regulation of uterine contractility. We hypothesize that NO affects both ET-1 or AVP. Therefore, this study investigated the involvement of extended exogenous NO release in the regulation of responses of the human non-pregnant myometrium to ET-1 and AVP. METHODS: Specimens were obtained from 10 premenopausal women, undergoing hysterectomy for benign gynecological disorders. Responses of the myometrial strips to ET-1 or AVP in the absence and presence of an exogenous NO donor (diethylenetriamine; DETA/NO; 10-4 mol/L) were recorded under isometric conditions. To inhibit endogenous NO, a competitive inhibitor of NO synthase, L-NG-nitroarginine (L-NNA) was added to the organ bath. RESULTS: ET-1 enhanced the spontaneous contractile activity of the myometrium more powerfully (p < 0.01) than AVP. Preincubation with exogenous NO weakened ET-1- or AVP-induced increases in this contractile activity (p < 0.05). However, unexpected results were obtained after preincubation with L-NNA and with DETA/NO then added. Both ET-1 and AVP induced augmented contractile effects in almost all concentrations compared with the responses to these peptides alone or after NOS synthase inhibition (both p < 0.01). CONCLUSIONS: This study demonstrated for the first time that extended incubation with a NO donor influences the uterine muscle response evoked by ET-1 and AVP. Both endogenous and exogenous NO is involved in the control of the uterine responses to ET-1 or AVP of non-pregnant myometrium. Furthermore, both peptides stimulate increased uterine contractility when the local imbalance between the constrictive and relaxing mediators takes place.

Atypical Endometrial Hyperplasia Arising in a Cesarean Section Scar: A Mechanism of Malignant Transformation.

The incidence of scar endometriosis in Cesarean sections varies between 0.03 and 0.4%. However, the recently increased rate of Cesarean sections worldwide may be causing an increase in occurrence of scar endometriosis. This report presents anatomopathological evidence of an early-stage malignant transformation in endometriotic tissue from a post-Cesarean scar and briefly reviews possible underlying mechanisms. A 40-year-old woman with a body mass index of 42.7 was referred to the gynecological department with recurrent pain and presence of a palpable mass in her Cesarean section scar. She had undergone this procedure 7 years earlier and began experiencing discomfort and pain at the incision site 6 months postoperatively. Surgical treatment was instituted with complete removal of the lesion. Anatomopathological examination revealed endometriotic tissue intertwined with atypical endometrial hyperplasia and fibrosis. At 2 years' follow-up, she was asymptomatic, both clinically and based on ultrasound examination. Endometriotic foci inoculated within an abdominal scar may undergo malignant transformation. Long-lasting abdominal scar endometriosis, in morbidly obese women, requires special attention from the physician.

Congenital vesicouterine fistulas-A PRISMA-compliant systematic review.

AIMS: Vesicouterine fistulas (VUFs) are infrequent abnormal connections between the bladder and the uterine cavity or cervical canal, being mainly sequelae of repeat Cesarean sections. Exceedingly rare are congenital VUFs. This is a systematic review of available world data aimed to characterize congenital VUFs and better understand the mechanism(s) of their formation. METHODS: The PubMed® database via MEDLINE® search engine was explored from its inception to March 2018. Relevant studies were identified using selected Medical Subject Heading-based terms. This was further supplemented by cross-referencing and handsearching. Retrieved literature was evaluated in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, or PRISMA, guidelines. RESULTS: A total of 6561 articles were identified of which 10 were analyzed. Three VUFs accompanied broader syndromes of congenital defects. A lack of patency at the level of the vagina was present in all assessed cases. Unilateral renal agenesis was confirmed in four of eight (50%) verified patients. Hence, unilateral kidney agenesis was related to a lesser degree (P = 0.0186) than vaginal atresia to VUF. The principal features of these fistulas were as follows: partial or complete vaginal atresia resulting in primary amenorrhea, menouria present since menarche, and urinary continence. CONCLUSIONS: This review provides the first systematic evidence that congenital VUFs are chiefly associated with concomitant vaginal atresia. The symptomatology of such VUFs is consistent with that of type I acquired fistulas.

Breast cancer in an 18-year-old female: A fatal case report and literature review.

Breast cancer (BC) is the most frequent malignancy in both pre- and postmenopausal women. However, it is exceedingly rare in very young patients, and especially in adolescents. Herein, we report a case of an 18-year-old female diagnosed with invasive BC. The proband had been found to be negative for BC in close family members. A common BC genetic screening test for the Polish population did not detect any known founder mutations in the BRCA1 gene. Further evaluation identified a p.Ile157Thr (I157T) mutation in the CHEK2 gene, a p.Ala1991Val (A1991V) variant of unknown significance in the BRCA2 gene, p.Lys751Gln (K751Q) variant in the XPD (ERCC2) gene, and a homozygous p.Glu1008Ter (E1008*) mutation in the NOD2 gene. No other mutation had been found by next generation sequencing in major BC high-risk susceptibility genes BRCA1, BRCA2, as well as 92 other genes. To date, all these found alterations have been considered as low to moderate risk factors in the general population and moderate risk factors in younger women (<35 years of age). There are no previous articles relating low and moderate risk gene mutations to very young onset (below 20 years) BC with a fatal outcome. In our patient, a possible cumulative or synergistic risk effect for these 4 alterations, and a mutation in the NOD2 gene in particular, of which both presumably healthy parents were found to be carriers, is suggested.

Expression of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors: Correlation with clinicopathological features.

BACKGROUND: The expression of p53 has been studied not only in primary human ovarian carcinomas, but also in borderline ovarian tumors, however, the results were discordant. Expression patterns of proteins involved in cell proliferation and apoptosis have been investigated in various human neoplasms, including female genital tract neoplasms. OBJECTIVE: The aim of this investigation was to assess the staining pattern and immunolocalization of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors (BOTs). DESIGN: The study group consisted of 42 women who underwent pelvic surgery between 2006-2015. The median patients' age was 46 years. The immunoperoxidase technique was employed using antibodies against p53, Ki-67, MCM3, PCNA, and topoisomerase IIα. RESULTS: For p53, nuclear expression was observed in BOTs, however, cytoplasmatic immunoreactivity was also detected. Altogether, 25 (60%) tumors demonstrated positive p53 immunostaining, including overexpression found in 6 (14%). There were no significant differences in p53 expression between subgroups of clinicopathological variables. Immunoexpression of Ki-67, MCM3, PCNA, and topoisomerase IIα was nuclear. Ki-67 expression was positive in 12 (29%) cases and there was a trend towards a relationship between patients' age and Ki-67 staining (P=0.08). Interestingly, a significantly higher Ki-67 expression was found in tumors of ≥10 cm in diameter compared to smaller tumors (P=0.008). MCM3 expression was detected in 38 (90%) tumors, and PCNA expression in 28 (67%), yet none of clinicopathological factors was related to them. Topoisomerase IIα expression was present in 14 (33%) cases and, interestingly, its significantly higher expression was observed in BOTs of ≥10 cm in diameter compared to smaller tumors (P=0.008). Moreover, Spearman's correlation revealed highly significant positive associations between Ki-67 and topoisomerase IIα (R=0.403, P=0.008) and Ki-67 and MCM3 (R=0.469, P=0.001). CONCLUSIONS: We report a high positive immunostaining rate for p53, suggesting a role of TP53 alterations in the development of BOTs in humans. The new finding of higher topoisomerase IIα immunostaining positivity in BOTs of ≥10 cm may be clinically relevant and requires further studies on larger patient groups.

Structural arrangement of vesicouterine fistula revisited: An immunohistochemical study documenting the presence of the endometrium.

Previous research has described a woman of reproductive age who presented with a vesicouterine fistula (VUF) of 20 months' duration. The VUF was lined with a metaplastic glandular epithelium containing both estrogen receptors (ER) and progesterone receptors (PR) in abundance. The aim of the present investigation was to evaluate the histology of the VUF canal when exposure to urine of the cellular elements within the fistula was of much shorter duration. A 41-year-old woman who developed a VUF during her third cesarean section was treated with transvesical fistula excision, electrocoagulation, and subsequent attempted hormonal treatment. Later, the patient underwent open surgery fistula repair. Postoperative specimens were subjected to anatomopathological examination together with immunohistochemical staining for ER and PR using monoclonal anti-human antibodies. Herein, we present for the first time detailed microscopic evidence that, at two separate timepoints, the fistulous tract was lined with the endometrium, which covered approximately 80% of the length of the VUF canal. In its intermediate segment, the urothelium formed an additional layer on the surface of the endometrium. At both timepoints, in the columnar epithelial and stromal endometrial cells lining the fistula, both ER and PR were present in abundance. In conclusion, VUF in subjects of reproductive age fulfill criteria for endometriosis. This study provides a rationale for the conservative treatment of VUF consistent with the hormonal treatment of endometriosis.

The Putative Role of TP53 Alterations and p53 Expression in Borderline Ovarian Tumors - Correlation with Clinicopathological Features and Prognosis: A Mini-Review.

Borderline ovarian tumors (BOTs) represent an independent group among ovarian malignancies, being diagnosed at clinical stage earlier than invasive ovarian carcinomas (OCs) and characterized by a rather favorable outcome after careful surgical management. Data published worldwide showed a substantial discordance of p53 expression in BOTs. The purpose of this work was to present the current status of knowledge on the significance of TP53 gene and p53 protein product alterations in BOTs. In general, higher p53 expression patterns were reported for ovarian malignancies compared to BOTs. Serous, mucinous, and endometrioid BOTs differ substantially in relation to p53 immunostaining, but data concerning the relationship between the protein's immunoreactivity and other clinico-pathological variables are scarce. Finally, reports published to date support the view that TP53 alterations may not be commonly associated with the borderline phenotype of ovarian tumors but they probably occur during the development of invasive OCs. In light of these uncertainties, the impact of TP53 alterations and p53 expression on overall survival in women affected by BOTs requires further multi-institutional studies in large cohorts of patients.

Competitive inhibition of amino acid transport in human preovulatory ovarian follicles.

To date we have yet to examine whether amino acid (AA) transport in human ovarian follicles is affected by competitive inhibition. In contrast, transplacental transfer of AAs in late-gestation sheep is characterized by reciprocal competition. This phenomenon has been described by algebraic equations of umbilical uptake of AAs based on maternal arterial concentrations. In the present translational study at a university teaching hospital, we verified whether these equations apply to the transport of AAs from blood to follicular fluid (FF) in human preovulatory follicles. For this purpose we used our data on AA concentrations in blood and FF measured earlier by high-performance liquid chromatography in specimens from 14 patients undergoing oocyte retrieval for in vitro fertilization after controlled ovarian stimulation. The main outcome measure was statistical significance of Spearman correlation coefficients for measured versus calculated concentrations of 8 AAs: isoleucine, leucine, valine, phenylalanine, methionine, threonine, lysine, and arginine. Equations for umbilical uptake provided a highly accurate description of blood-to-FF transport for 7 AAs with the exception of lysine: R ≥ 0.899 (p < 0.0001) for the branched-chain AAs, R = 0.829 (p = 0.0003) for threonine, R = 0.754 (p = 0.0019) for arginine, and R = 0.631 (p = 0.0156) for phenylalanine and methionine. We conclude that these equations indicate competitive inhibition between the AAs studied. Our study strongly suggests that many AA transport systems operating in the placenta should also be active in the cells of the preovulatory follicle. Future studies on AA fluxes in human ovarian follicles must consider possible competitive inhibition. ABBREVIATIONS: AA: amino acid; FF: follicular fluid; HPLC: high-performance liquid chromatography.

Altered uterine contractility in response to ß-adrenoceptor agonists in ovarian cancer.

We aimed to prospectively examine ß-adrenoceptor-mediated uterine contractility in women suffering from gynecological malignancies. Myometrial specimens were obtained from non-pregnant women undergoing hysterectomy for benign gynecological disorders, and ovarian, endometrial, synchronous ovarian-endometrial, and cervical cancer. Contractions of myometrial strips in an organ bath before and after cumulative dosages of ß2- and ß3-adrenoceptor agonists with preincubation of propranolol, SR 59230A, and butoxamine were studied. All agonists induced a dose-dependent attenuation for uterine contractility in endometrial or cervical cancer, similar to that observed in the reference group. Contradictory effects were observed for ovarian cancer alone or in combination with endometrial cancer. CL 316243 or ritodrine abolished the relaxation, whereas BRL 37344 increased the uterine contractility in ovarian cancer. Moreover, ß-adrenoceptor antagonists caused varied effects for ß2- or ß3-adrenoceptor agonists. Our experiments demonstrate that ovarian cancer, alone or as synchronous ovarian-endometrial cancer, substantially alters uterine contractility in response to ß-adrenoceptor agonists.

[Levonorgestrel-releasing intrauterine system Mirena® (Bayer) for the prevention and treatment of endometrial adenocarcinoma and the incidence of other malignancies in women]. / Wplyw systemu wewnatrzmacicznego uwalniajacego lewonorgestrel Mirena® (Bayer) na prewencje i leczenie raka gruczlowego blony sluzowej macicy oraz na inne nowotwory zlosliwe u kobiet.

The use of hormone-releasing intrauterine devices has been on the increase for the last three decades. To date, evidence of their long-term efficiency is available. The aim of the present paper was to briefly review beneficial prophylactic effects of the levonorgestrel-releasing intrauterine system on the incidence of a variety of malignancies in women. Such an influence is of a particular importance in the light of the currently observed increased prevalence of endometrial and cervical adenocarcinomas. Low-dose releasing intrauterine systems are also available, but the hard evidence-based medical data have been derived primarily for Mirena® (Bayer) device, which topically releases from 20 to 14 pg of levonorgestrel daily. Consequently the risk of developing endometrial carcinoma in Mirena® users is lowered by as much as 50% compared with the general population risk To a lesser extent, the intrauterine system decreases the risk for cervical adenocarcinoma and squamous cell carcinoma, as well as ovarian, pancreas, and lung carcinomas. In one population-based study Mirena® increased the risk for breast carcinoma by approximately 20%, whereas a number of other studies failed to demonstrate such a hazard. In the recent decades of the increased predominance of insulin resistance and obesity and an occurrence of hormone-dependent carcinomas at earlier age, a broad application of levonorgestrel-releasing intrauterine systems may become a particularly important component of primary prevention of malignancies in women. Both obese and overweight patients seem perfect candidates for such a hormonal intervention.

An Open Multicenter Study of Clinical Efficacy and Safety of Urolastic, an Injectable Implant for the Treatment of Stress Urinary Incontinence: One-Year Observation.

The prevalence of stress urinary incontinence rises and affects up to 30% of women after 50 years of age. Midurethral slings are currently the mainstay of surgical anti-incontinence therapy. Some patients experience recurrent SUI (RSUI) which is defined as a failure of anti-incontinence surgery after a period of time or persistence of SUI after the procedure aimed at correcting it. The urethral bulking agent application decreases invasiveness of treatment and meets patients requirements. The objective of this study was to assess the safety and clinical efficacy of Urolastic injection. One hundred and five patients with SUI (including 91 patients with RSUI) were treated with Urolastic in three tertiary gynecological clinics. The efficacy of the procedure was assessed objectively at each follow-up visit by means of cough test and a standard 1-hour pad test. Objective success rate after 12 months after primary procedure in RSUI patients was found in 59.3% of patients. In 14 patients with primary SUI improvement after 1 year was found in 71.4% of patients. Although cure rates after MUS are up to 90% there is still place for less invasive treatment option like periurethral injection of bulking agents, especially in patients with previous SUI surgical management.

Surface antigen expression on peripheral blood monocytes in women with gynecologic malignancies.

BACKGROUND: Of many specialized blood cells, monocytes are gaining increasing attention for their role in neoplastic disorders. The purpose of the present investigation was to determine the expression of selected peripheral blood monocyte surface antigens in cases of cervical, endometrial, and ovarian cancers. In addition, our aim was to validate the diagnostic value of two artificial coefficients recently proposed for the diagnosis of gynecologic malignancies: Neutrophil to Lymphocyte Ratio (NLR), and Multiplication of Neutrophil and Monocyte Counts (MNM). METHODS: We studied 69 white Caucasian women with histopathologic confirmation of endometrial (N = 42), cervical (N = 13), and ovarian (N = 14) cancers. Reference Group I were women suspected of cancer but histologically nullified (N = 20), and Group II were healthy blood donors (N = 23). Expression of CD11a, CD11b, CD11c, CD16, CD54 (ICAM-1), CD62 L (L-selectin), CD64, and HLA-DR was measured with immunofluorescence in a flow cytometer. RESULTS: CD54 expression increased by ≥35.6% (p < 0.001) whilst HLA-DR decreased by ≥10.8% (p < 0.001) in all cancer subgroups and Group I as compared to blood donors. A correlation (p < 0.05) between CD54 and CD62 L was stronger in all cancers studied than in healthy subjects. There was no difference in the NLR values between any of these subgroups. Moreover, we observed an increase in MNM parameter in cases of cervical and endometrial cancer and in the Reference Group I. CONCLUSIONS: In the studied gynecologic malignancies, CD54 expression on peripheral blood monocytes is enhanced, indicating a higher transmigrational potential present in such patients, and HLA-DR expression diminished, indicating a decreased readiness of the immune system to recognize foreign antigens. The more pronounced correlation for the expression of CD54 and CD62 L in cancer suggests that monocytes uptake from the bloodstream and their local adhesion increase the pool of tumor-associated macrophages. This study challenged the suggested credibility and usefulness of the artificial parameters of MNM and NLR for the differential diagnosis of gynecologic malignancies.

Coexistence of homologous-type cervical carcinosarcoma with endometrioid-type G1 endometrial cancer: a case report with an immunohistochemical study.

Coexistence of two or even more independent primary tumors derived from the female genital tract organs is a unique event. The most common combination is the coexistence of synchronous tumors in the ovary and endometrium. In the present case study, we described a coincidence of homologous-type cervical carcinosarcoma (CS) with endometrioid-type G1 uterine adenocarcinoma (EC) arising on the basis of hyperplastic endometrium. A panel of immunohistochemical markers was applied, either in both CS components or in endometrioid-type EC, to assess possible differences between both uterine malignancies. We also presented a short overview of the coexistence of cervical carcinosarcomas with other female genital tract malignancies.

Giant vulvar lipoma in an adolescent girl: a case study and literature review.

A rare case of a giant vulvar lipoma that developed in an adolescent is presented. A review of the world literature of 15 cases that occurred prior to adulthood confirmed that they tend to occur on the right side of the vulva.

p53 is not related to Ki-67 immunostaining in the epithelial and mesenchymal components of female genital tract carcinosarcomas.

Carcinosarcomas (CSs) are composed of two separate histological components and are rare neoplasms of the female genital tract. Therefore, CS pathogenesis has not yet been fully elucidated. In the present study, immunohistochemical techniques were used to determine the role of p53 and Ki-67 overexpression in female genital tract CSs. The study group was comprised of 36 patients with CSs originating from the uterus (n=31), cervix (n=3) and ovary (n=2), as well as 3 metastatic tissues. p53 was overexpressed in the epithelial component of 23 out of 36 (64%) tumors, and in the mesenchymal component of 20 out of 36 (56%) tumors. In both CS components, there was a significant correlation between p53 overexpression and patient age and ovarian metastases. Ki-67 overexpression was detected in the epithelial component in 15 out of 36 (42%) cases, and in the mesenchymal component in 13 out of 36 (36%) neoplasms. There was a significant correlation of p53 overexpression between the carcinomatous and sarcomatous components (R=0.884, P<0.001). A significant correlation was also found in Ki-67 immunoreactivity between the two CS components (R=0.676, P<0.001). However, p53 overexpression was not correlated with Ki-67 immunostaining in both tumor components. In conclusion, based on immunohistochemical results, p53 was overexpressed in more than half of the female genital tract CSs included in the present study, either at the epithelial or mesenchymal component. The correlation between p53 or Ki-67 overexpression in both tumor components supports the combination theory of histogenesis in the majority of these tumors.