Expression Patterns of Cytokeratins (CK7, CK20, CK19, CK AE1/AE3) in Atypical Endometrial Hyperplasia Coexisting with Endometrial Cancer.

Few studies have evaluated cytokeratin's (CK) staining patterns in atypical endometrial hyperplasia (AEH) coexisting with early-stage endometrial cancer (EC). We aimed to assess the staining patterns of selected CKs (CK7, CK19, CK20, CK AE1/AE3) in 74 patients with coexisting AEH and EC by independently analyzing both morphological variables. Specimens were collected from women with AEH and EC who underwent surgical interventions between 2012 and 2019 at the Department of Obstetrics and Gynecology of Vilnius University Hospital "Santaros Klinikos" in Vilnius, Lithuania. Immunostaining was also qualitatively classified as being heterogeneous or intense. The results revealed heterogeneous CK7 expression in all AEH cases and intense staining in 95.95% cases of AEH. The heterogeneous expression of CK7 was detected in all EC specimens. Intense CK7 expression was observed in 95.09% cases of EC G1 and in all G2 ECs. Heterogenous CK19 expression was present in all AEH specimens with intense staining in 92.42% of cases. Heterogeneous CK19 expression was observed in all EC samples with intense expression in 86.27% cases of EC G1 and 100% cases of EC G2. Interestingly, a significant relationship was found when comparing the heterogeneous expression of CK19 between AEH and well-differentiated EC. A significant difference was reported in the intense expression of CK AE1/AE3 (p = 0.031; p = 0.029) between AEH and G2 ECs and in the intense expression of CK AE1/AE3 between G1 and G2 ECs. CK20 staining was not a characteristic feature for AEH and early-stage EC. CK staining is present either in AEH or in early-stage endometrioid-subtype EC in different manners. Heterogeneous CK19 expression was significantly more common in AEH than in EC. CK20 expression was not associated with either AEH nor early-stage EC. An intense expression of CK AE1/AE3 was mainly present in moderately differentiated ECs, whereas the intense reactivity of AE1/AE3 showed a significant difference in well to moderately differentiated uterine tumors. The clinical implication of CK staining may aid in the more accurate diagnosis of AEH and early-stage EC as well as detect micrometastases leading to better oncological outcomes.

Antioxidative, Anti-Inflammatory, Anti-Obesogenic, and Antidiabetic Properties of Tea Polyphenols-The Positive Impact of Regular Tea Consumption as an Element of Prophylaxis and Pharmacotherapy Support in Endometrial Cancer.

Endometrial cancer (EC) is second only to cervical carcinoma among the most commonly diagnosed malignant tumours of the female reproductive system. The available literature provides evidence for the involvement of 32 genes in the hereditary incidence of EC. The physiological markers of EC and coexisting diet-dependent maladies include antioxidative system disorders but also progressing inflammation; hence, the main forms of prophylaxis and pharmacotherapy ought to include a diet rich in substances aiding the organism's response to this type of disorder, with a particular focus on ones suitable for lifelong consumption. Tea polyphenols satisfy those requirements due to their proven antioxidative, anti-inflammatory, anti-obesogenic, and antidiabetic properties. Practitioners ought to consider promoting tea consumption among individuals genetically predisposed for EC, particularly given its low cost, accessibility, confirmed health benefits, and above all, suitability for long-term consumption regardless of the patient's age. The aim of this paper is to analyse the potential usability of tea as an element of prophylaxis and pharmacotherapy support in EC patients. The analysis is based on information available from worldwide literature published in the last 15 years.

Retrospective Comparison of Laparoscopic versus Open Radical Hysterectomy for Early-Stage Cervical Cancer in a Single Tertiary Care Institution from Lithuania between 2009 and 2019.

Background and Objectives: A great debate within the academic arena was evoked by the LACC study, giving rise to doubt regarding the oncological outcomes of the laparoscopic approach for early-stage cervical cancer. This encouraged us to conduct a retrospective analysis of CC treatment surgical approaches applied to the patients at tertiary level Vilnius University Hospital Santaros Clinics, Vilnius, Lithuania, between 2009 and 2019. Materials and Methods: The retrospective study was carried out to evaluate the outcomes after 28 laparoscopic and 62 laparotomic radical hysterectomies for early cervical cancer in a single tertiary care institution performed during the period 2009-2019. For statistical analysis of patients' parameters, SPSS v. 17.0 was applied, together with the Kaplan-Meier method with a long-rank test and the Cox proportional hazard regression model used for bi-variate analysis determining OS outcomes between MIS and open-surgery groups. Results: After computing data with the Cox regression model, there was no significant difference of the 36-months overall survival between laparoscopy and laparotomy groups, as opposed to the LACC study. Conclusions: Our tertiary institution faces a considerable challenge, and we acknowledge the limitations of the study and also feel a responsibility to follow the latest guidelines. Currently, it appears that the most substantial attention should be focused on the cessation of uterine manipulator use as well as laparoscopic technique learning curves.

Laparoscopic Radical Trachelectomy after Neoadjuvant Chemotherapy for Fertility Preservation in Early-Stage Bulky Cervical Cancer: A Case Report and Literature Review.

Management of early-stage cervical cancer (CC) in young women often faces challenges to preserve fertility, as well as to achieve an adequate oncological outcome. Although existing evidence supports a fertility-sparing treatment in the case of tumors <2 cm in diameter, the approach is less clear in bulky early-stage CC. In addition, the outcomes of radical trachelectomy performed by minimally invasive techniques are also highly debatable. Highlighting the high incidences of young women with early-stage CC, the lack of sufficient data raises considerable hindrances towards the proper counseling of this vulnerable patient group. In this report, a case of a young woman with bulky early-stage CC with a strong desire to preserve fertility is presented. A satisfactory oncological outcome was achieved after neoadjuvant chemotherapy followed by laparoscopic radical trachelectomy. Ongoing prospective trials are expected to provide stronger evidence on this topic.

Serum paraoxonase 1 activity and protein N-homocysteinylation in primary human endometrial cancer.

Paraoxonase 1 plays an important role in protection from oxidative stress and also decomposes homocysteine thiolactone, the toxic metabolite of homocysteine. A limited number of reports evaluated the role of paraoxonase 1 in women affected by female genital tract neoplasms, including endometrial cancer. This study aimed to analyze the paraoxonase activity in the group of endometrial cancer patients (n = 48) who underwent primary surgery and to compare the data available with a well-matched control group (n = 30). Due to the role of paraoxonase 1 in the metabolism of homocysteine (Hcy) thiolactone, the amount of Hcy-thiolactone as well as total serum Hcy concentrations was also measured. Serum paraoxonase 1 activity toward synthetic substrates, paraoxon and phenyl acetate, in the study group was significantly lower compared to the control one. The mean paraoxonase 1 activity toward homocysteine thiolactone tended to be lower in the endometrial cancer group but this difference was not significant. There was no relationship between endometrial cancer and Q192R polymorphism of PON1 assessed by the dual substrate method. No differences in paraoxonase 1 activity between endometrial cancer subgroups according to clinico-pathological features were detected. Total serum homocysteine and protein-bound homocysteine thiolactone did not differ between control and cancer groups. In conclusion, reduced paraoxonase 1 activity suggests diminished important antioxidant mechanisms during the development of primary endometrial cancers in humans. PON1 Q192R polymorphism is not associated with the risk of endometrial cancer. Despite lower paraoxonase 1 activity, homocysteine concentration, and protein N-homocysteinylation in endometrial cancers do not differ from matched controls.

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.

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.

Prognostic Parameters for Patients with Cervical Cancer FIGO Stages IA2-IIB: A Long-Term Follow-Up.

OBJECTIVE: We assessed the prognostic factors related to 10-year overall survival and disease-free survival in cervical cancer patients that underwent primary surgical protocols in 1 institution. MATERIALS AND METHODS: A total of 102 patients with uterine cervical cancer at FIGO stages IA2-IIB that underwent a Piver type III radical hysterectomy and pelvic lymphadenectomy between 1998 and 2001 were included. Univariate and multivariate analyses of 10-year overall survival and 10-year disease-free survival were performed. RESULTS: Univariate analysis revealed that only lymphovascular space invasion significantly affected 10-year overall survival (p = 0.04), but it had no effect on the 10-year disease-free survival rate. Multivariate analysis demonstrated that survival rates were significantly affected by FIGO stage (p = 0.02, 95% CI: 1.18-5.55, for 10-year overall survival; p = 0.03, 95% CI: 1.07-6.12, for 10-year disease-free survival) and metastases to the pelvic lymph nodes (p = 0.0005, 95% CI: 1.81-8.53, for 10-year overall survival; p = 0.01, 95% CI: 1.26-7.24, for 10-year disease-free survival). CONCLUSIONS: The only independent prognostic factors for 10-year survival rates in patients with cervical cancer at FIGO stages IA2-IIB were clinical stage and presence of metastases to the pelvic lymph nodes. The presence of lymphovascular space invasion adversely affected 10-year overall survival.

Prediction of 5-year overall survival in cervical cancer patients treated with radical hysterectomy using computational intelligence methods.

BACKGROUND: Computational intelligence methods, including non-linear classification algorithms, can be used in medical research and practice as a decision making tool. This study aimed to evaluate the usefulness of artificial intelligence models for 5-year overall survival prediction in patients with cervical cancer treated by radical hysterectomy. METHODS: The data set was collected from 102 patients with cervical cancer FIGO stage IA2-IIB, that underwent primary surgical treatment. Twenty-three demographic, tumor-related parameters and selected perioperative data of each patient were collected. The simulations involved six computational intelligence methods: the probabilistic neural network (PNN), multilayer perceptron network, gene expression programming classifier, support vector machines algorithm, radial basis function neural network and k-Means algorithm. The prediction ability of the models was determined based on the accuracy, sensitivity, specificity, as well as the area under the receiver operating characteristic curve. The results of the computational intelligence methods were compared with the results of linear regression analysis as a reference model. RESULTS: The best results were obtained by the PNN model. This neural network provided very high prediction ability with an accuracy of 0.892 and sensitivity of 0.975. The area under the receiver operating characteristics curve of PNN was also high, 0.818. The outcomes obtained by other classifiers were markedly worse. CONCLUSIONS: The PNN model is an effective tool for predicting 5-year overall survival in cervical cancer patients treated with radical hysterectomy.

Should we be more aware of endometrial cancer in adolescents?

Although endometrial cancer is generally diagnosed in women after menopause, it may incidentally develop in young women or even in adolescents. Diagnostic tools should be applied in young teenage girls complaining of abnormal genital bleeding, particularly those with hereditary cancer syndromes (such as Cowden or Lynch syndromes). Adolescents affected by polycystic ovary syndrome and obesity may also be at increased risk for the development of atypical endometrial hyperplasia and endometrial cancer, and should be carefully managed when the distressing symptoms occur. In the present article, we briefly summarize the principal clinical correlates associated with endometrial cancer in adolescents.

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.

Role of p53 pathway alterations in uterine carcinosarcomas (malignant mixed Müllerian tumors).

Carcinosarcomas (CSs; malignant mixed Müllerian tumors) of the uterus are highly malignant neoplasms characterized by an unfavorable outcome. They represent less than 5% of all uterine malignancies, and the median patient survival rate is only 21 months. p53 pathway alterations have been studied in CSs originating from the uterus, supporting the monoclonal nature of most but not all of these neoplasms. This paper gives an overview of the current knowledge of p53 pathway distortions in patients with uterine CSs. The survival of patients with uterine CSs in relation to p53 pathway alterations is also briefly summarized.

Diagnostic difficulties in the differentiation between an ovarian metastatic low­grade appendiceal mucinous neoplasm and primary ovarian mucinous cancer: A case report and literature review.

Low-grade appendiceal mucinous neoplasm (LAMN) is a tumor that primarily originates from the appendix and belongs to the family of appendiceal mucinous neoplasms (AMNs). In 50% of female patients, AMNs (particularly LAMNs) have a tendency to metastasize to organs in the genital tract, where the neoplasm can mimic the features of primary ovarian mucinous cancer (POMC). The present case report reviewed the difficulties in differentiating between these two types of tumors. In the present case report, a 61-year-old female patient was admitted to the Second Department of Gynecological Surgery and Gynecological Oncology, University Clinical Hospital no. 4 at Lublin Medical University (Lublin, Poland) with the diagnosis of a right ovarian mass. After performing ultrasound and computed tomography (CT) scans and laboratory analysis, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy and resection of the Douglas peritoneum. Notably, the postoperative pathological assessment revealed LAMN with metastases to the right ovary and omentum. Immunohistochemically, cytokeratin 20 and caudal type homeobox 2 both stained positively, whereas paired box gene 8 stained negatively. After surgery, the patient received the recommended hyperthermic intraperitoneal chemotherapy at the Department of Surgical Oncology at Lublin Medical University. After 1 year, a CT scan was performed, which indicated no evidence of recurrent disease. In conclusion, observations from the present case report suggest that gynecologists should be conscious of the possibility of malignancies of gastrointestinal origin in cases of ovarian tumors instead of making direct assumptions of POMC. If the mucinous mass involves the base of the appendix or if there is a suspicion of positive margins, then cytoreductive surgery and right-sided hemicolectomy must be performed. In addition, identifying the origin of mucinous tumors in the right ovary and/or the appendix requires the histopathological examination of a panel of markers using immunohistochemistry.

Methylation of the Selected TP53 Introns in Advanced-Stage Ovarian Carcinomas.

Objective: Advanced-stage ovarian cancer (OC) is among the most fatal female genital tract neoplasms worldwide. Although different genetic mechanisms have been shown to be involved in ovarian carcinogenesis, the role of TP53 introns methylation is still unresolved. We performed methylation analysis of introns 1, 3, and 4 of the TP53 to identify patterns in primary stage III OCs, corresponding metastases, and healthy tissues. Methods: The study involved samples of paraffin-embedded tissues obtained from 80 patients with stage III OCs, who underwent surgery at the Department of Gynecology and Gynecologic Oncology of the Military Institute of Medicine in Warsaw, Poland. Altogether, 40 serous-type G2/3 OCs and 40 endometrioid-type G2/3 OCs were included. From the same patient, metastatic and normal tissues were simultaneously analyzed. As a control group, 80 tissue samples were collected from patients after bariatric operations. Human ovarian cancer A2780 cell line was also investigated. Total genomic DNA was isolated from paraffin-embedded tissue blocks and the methylation analysis was performed by bisulfite DNA conversion, DNA amplification with specific primers, cloning, and DNA sequencing. Results: All of the samples of intron 1 of TP53 were un-methylated in OCs, metastatic tissues, and in healthy tissues from the same patient. Also, no methylation of TP53 intron 1 was detected in cells from the human A2780 ovarian cancer cell line and in all samples from control group. In all samples, introns 3 and 4 of the TP53 were methylated in primary tumors, metastatic tissue, and in healthy tissue from the same patient, in human A2780 ovarian cell line, and in DNA samples from healthy patients. None of the clinicopatholocal features was related to the TP53 introns methylation status. Conclusions: Our data on TP53 introns methylation sheds new light on the mechanism of p53 activity for a better understanding of cancer biology. The study suggests the existence of an additional regulation rule of TP53 activity that involves demethylation-methylation mechanisms. Methylation at introns 3 and 4 may also overall help in protecting TP53 against damage by viral restrictases or viral DNA integration.

GPER-1 expression decreases during breast cancer tumorigenesis.

GPER-1 protein expression was immunohistochemically examined in 164 primary breast cancer specimens and their matched normal breast epithelium. GPER-1 down-regulation correlated significantly with increased histological grading (p = .015), lymph node metastases (p = .032), and negative estrogen receptor status (p = .018). The decrease of GPER-1 expression in breast cancer tissue, relative to normal tissue, was associated with poor overall survival (p = .043) and disease-free survival (p = .037) and remained a significant unfavorable factor in multivariate analysis for DFS (HR = 1.569; 95% CI, 1.024-2.797; p = .041) and OS (HR = 2.082; 95% CI, 1.248-4.773; p = .039). Thus aberrant GPER-1 expression seems to be an important factor in breast cancer progression.

[Level of satisfaction in patients giving birth in Poland/Rzeszów and in the Federal Republic of Germany/Gross-Gerau]. / Satysfakcja z opieki okoloporodowej pacjentek rodzacych w Polsce/Rzeszow i w Republice Federalnej Niemiec/Gross-Gerau.

AIM OF THE STUDY: The main purpose of the study was to examine opinions on perinatal care expressed by women hospitalized after childbirth in Poland and Germany Different socio-demographic variables were also analyzed in order to evaluate the quality of perinatal care in two different countries. MATERIALS AND METHODS: The study group comprised of postpartum patients from two facilities: the Clinical Ward of Gynecology and Obstetrics of Frideric Chopin Province Specialist Hospital in Rzeszów, Poland, and the Obstetrics-Gynecology Hospital in Gross-Gerau, Germany The group of randomly selected women, who were initially invited to participate in the study included 259 Polish and 230 German females. In order to measure the level of satisfaction with perinatal care, the authors used "The Newcastle Satisfaction with Nursing Scale" (originally constructed at the Center for Health Services Research, "University of Newcastle upon Tyne, UK, and adopted in Poland by Poznan University of Medical Sciences) and their own questionnaire. Finally 200 patients, one hundred from Poland and one hundred from Germany were enclosed. Statistical analysis was performed using the Statistics 8.0 software and a p valued below 0.05 was regarded significant. RESULTS: Generally perinatal care was assessed as being satisfactory by both Polish (91%) and German (97%) respondents. The study population varied in terms of age, education, place of residence or marital status. Only one socio-demographic variable (education) had a significant impact on the perception of the obtained perinatal care. However a limited number of patients (25% in Poland and 47% in Germany) participated in the prental and parenting classes. CONCLUSIONS: 1. Perinatal care was positively assessed by Polish and German patients of both hospitals. 2. The greatest importance in selecting the location for childbirth was attributed by both Polish and German subjects to such factors as: opinion of their friends, highly qualified personnel, modern medical equipment and instruments on premises. Additionally Polish respondents found it important that the doctor who had provided care for a given woman during pregnancy was employed at that particular hospital. In turn, German respondents also paid particular attention to the distance between their place of residence and hospital. 3. All study participants, regardless of their nationality admitted that the hospitals offered to their close relatives the possibility to visit and accompany the patients during childbirth.

HPV16 E6 Gene Transcripts in Primary Type II Endometrial Carcinomas.

BACKGROUND/AIM: Data on the prevalence of human papilloma virus (HPV) DNA in different subtypes of endometrial carcinomas (EC) are limited. PATIENTS AND METHODS: We investigated the incidence of HPV16 DNA E6/E7 transcripts in 47 type I (endometrioid-type) tumors and eight type II (non-endometrioid-type) uterine neoplasms applying PCR-based technology. Immunohistochemical staining in HPV16 positive cases was also performed, and seven lymph node metastases were examined for the presence of HPV16 DNA E6/E7. RESULTS: None of the type I ECs was positive for HPV16 E6 gene transcripts; however, four out of 8 (50%) type II ECs (two out of four papillary-serous and two out of four clear-cell carcinomas) were positive for HPV16 E6 transcripts. The difference in HPV16 E6 transcripts between endometrioid and non-endometrioid neoplasms was statistically significant (p=0.0011). Apart from the cancer subtype, none of the EC clinicopathological features were related to HPV16 E6 positivity. None of 55 ECs contained an HPV16 E7 gene transcripts. All slides from gene-positive samples revealed intense immunostaining reactions. Interestingly, the virus was not detected in any of seven lymph node metastases, including four from HPV16-positive primary tumors. CONCLUSION: HPV16 E6 gene transcripts may be present in ECs, primarily in the non-endometrioid (type II) uterine cancer subtypes. HPV E6/E7 DNA transcripts were not found in lymph node metastases, even when the primary tumors harboured HPV DNA.

Synchronously occurring endometrioid carcinomas of the uterine corpus and uterine cervix preceded by different precancerous lesions: A case study and a literature review.

The incidence of two synchronous carcinomas originating from the uterine corpus and uterine cervix, both endometrioid subtypes, is exceedingly rare. Herein, we presented synchronous early stage G1 adenocarcinoma of the uterine corpus with cervical G2 endometrioid adenocarcinoma. Although both neoplasms displayed the same histological subtype, they differed significantly according to the histological grading or clinical stage of the disease. Finally, it is worth emphasizing that both tumors were preceded by different precancerous lesions, atypical endometrial hyperplasia (AEH) and foci of endometriosis localized within the uterine cervix. Although AEH is a well-known precancerous condition of endometrioid carcinoma, the mechanisms resulting in the malignant transformation of endometriosis foci to the cervical endometrioid carcinoma are still a matter of controversy. We briefly summarized the impact of different precancerous lesions on the development of synchronous female genital tract neoplasms with the same histotype.

Endometrial cancer diagnostic and prognostic algorithms based on proteomics, metabolomics, and clinical data: a systematic review.

Endometrial cancer is the most common gynaecological malignancy in developed countries. Over 382,000 new cases were diagnosed worldwide in 2018, and its incidence and mortality are constantly rising due to longer life expectancy and life style factors including obesity. Two major improvements are needed in the management of patients with endometrial cancer, i.e., the development of non/minimally invasive tools for diagnostics and prognostics, which are currently missing. Diagnostic tools are needed to manage the increasing number of women at risk of developing the disease. Prognostic tools are necessary to stratify patients according to their risk of recurrence pre-preoperatively, to advise and plan the most appropriate treatment and avoid over/under-treatment. Biomarkers derived from proteomics and metabolomics, especially when derived from non/minimally-invasively collected body fluids, can serve to develop such prognostic and diagnostic tools, and the purpose of the present review is to explore the current research in this topic. We first provide a brief description of the technologies, the computational pipelines for data analyses and then we provide a systematic review of all published studies using proteomics and/or metabolomics for diagnostic and prognostic biomarker discovery in endometrial cancer. Finally, conclusions and recommendations for future studies are also given.

The most likely but largely ignored triggering factor for breast (or all) cancer invasion.

Breast cancer development and progression are believed to be a sequential process, from normal to hyperplastic, to in situ, and to invasive and metastatic stages. Given that over 90% of cancer deaths are caused by invasive and metastatic lesions, countless factors and multiple theories have been proposed as the triggering factor for the cascade of actions of cancer invasion. However, those factors and theories are largely based on the studies of cell lines or animal models. In addition, corresponding interventions based on these factors and theories have failed to reduce the incidence rate of invasive and metastatic lesions, suggesting that previous efforts may have failed to arm at the right target. Considering these facts and observations, we are proposing "A focal aberrant degeneration in the myoepithelial cell layer (MECL) as the most likely triggering factor for breast cancer invasion". Our hypothesis is based on our recent studies of breast and multiple other cancers. Our commentary provides the rationale, morphologic, immunohistochemical, and molecular data to support our hypotheses. As all epithelium-derived cancers share a very similar architecture, our hypothesis is likely to be applicable to invasion of all cancer types. We believe that human tissue-derived data may provide a more realistic roadmap to guide the clinic practice.