Types Of Endometrial Cancer Research Articles

Evaluation of ultrasound endometrial stripe thickness in uterine serous carcinoma

Uterine serous carcinoma (USC) is a rare type of endometrial cancer representing less than 10% of uterine cancers, but contributes to up to 50% of the mortality. USC can occur in the setting of a thin, atrophic endometrium. National guidelines support the use of transvaginal ultrasound as one option for initial triage in the evaluation of a woman with postmenopausal bleeding. If the endometrial stripe (EMS) is ≤4 mm, biopsy can be avoided if no further bleeding occurs. We sought out to further investigate the EMS thickness in USC in order to assess the reliability of the current guidelines in this cancer.

Anti-Müllerian Hormone Type II Receptor Expression in Endometrial Cancer Tissue.

Anti-Müllerian hormone (AMH) is responsible for the Müllerian ducts’ regression in male fetuses. In cells of cancers with AMH receptors (AMHRII), AMH induces cell cycle arrest or apoptosis. As AMH occurs naturally and does not exhibit significant side effects while reducing neoplastic cell colonies, it can be considered as a potential therapeutic agent for cancer treatment. The purpose of this study was to assess the AMHRII expression in endometrial cancer (EC) in correlation to various demographic data and clinical conditions. Immunohistochemical analysis was used to assess AMHRII expression in EC tissue samples retrieved from 230 women with pre-cancerous state of endometrium (PCS) and EC. AMHRII was detected in 100% of samples. No statistical difference was observed for AMHRII expression depending on the histopathological type of EC, cancer staging, body mass index, and age, as well as the number of years of menstruation, births and miscarriages, and average and total breastfeeding time. Diabetes mellitus type 2 is the only factor that has an impact on AMHRII expression in EC tissue. Thus, this study supports the idea of theoretical use of AMH in EC treatment because all histopathological types of EC at all stages of advancement present receptors for AMH.

Establishment and characterization of VOA1066 cells: An undifferentiated endometrial carcinoma cell line.

Dedifferentiated endometrial carcinoma (DDEC) is a rare but highly aggressive type of endometrial cancer, in which an undifferentiated carcinoma arises from a low-grade endometrioid endometrial carcinoma. The low-grade component is often eclipsed, likely due to an outgrowth of the undifferentiated component, and the tumor may appear as a pure undifferentiated endometrial carcinoma (UEC). We and others have recently identified inactivating mutations of SMARCA4, SMARCB1 or ARID1B, subunits of the SWI/SNF chromatin-remodeling complex, that are unique to the undifferentiated component and are present in a large portion of DDEC and UEC. However, the understanding of whether and how these mutations drive cancer progression and histologic dedifferentiation is hindered by lack of cell line models of DDEC or UEC. Here, we established the first UEC cell line, VOA1066, which is highly tumorigenic in vivo. This cell line has a stable genome with very few somatic mutations, which do include inactivating mutations of ARID1A and ARID1B (2 mutations each), and a heterozygous hotspot DICER1 mutation in its RNase IIIb domain. Immunohistochemistry staining confirmed the loss of ARID1B, but ARID1A staining was retained due to the presence of a truncating non-functional ARID1A protein. The heterozygous DICER1 hotspot mutation has little effect on microRNA biogenesis. No additional DICER1 hotspot mutations have been identified in a cohort of 33 primary tumors. Therefore, we have established the first UEC cell line with dual inactivation of both ARID1A and ARID1B as the main genomic feature. This cell line will be useful for studying the roles of ARID1A and ARID1B mutations in the development of UEC.

Tamoxifen and Endometrial Cancer: A Janus-Headed Drug.

Simple SummaryTamoxifen, an antiestrogen, is a potent drug to treat and prevent hormone dependent breast cancer. As it has low toxicity and is widely available, tamoxifen has become one of the most frequently prescribed anticancer drugs worldwide. A major side effect of tamoxifen is to increase the risk of uterine corpus cancer (endometrial cancer). This happens after long-term (>2 years) application, especially in postmenopausal women with preexisting pathologies in the uterus. On the other hand, tamoxifen is an efficacious treatment for certain forms of advanced endometrial cancer, thus making it a Janus-headed drug that can support the development of endometrial cancer on one hand and be used as a remedy for this disease on the other. This article reviews the clinical data on these controversial effects of tamoxifen and the possible explanations.Tamoxifen is a selective estrogen receptor modulator used for the treatment and prevention of estrogen receptor (ER)—positive breast cancer. However, tamoxifen increases the risk of endometrial cancer (EC) by about 2–7 fold, and more aggressive types of EC with poor prognoses are observed in tamoxifen users. On the other hand, tamoxifen is an efficacious treatment for advanced or recurrent EC with low toxicity. The differential agonistic or antagonistic effects of tamoxifen on ERα are explained by the tissue-specific expression profiles of co-activators and co-repressors of the receptor. The estrogen-agonistic effect of tamoxifen in endometrial cancers can also be explained by the expression of G-protein coupled estrogen receptor 1 (GPER-1), a membrane-bound estrogen receptor for which tamoxifen and other “antiestrogens” are pure agonists.

Abstract 3490: Investigation of 27-hydroxycholesterol as a biomarker for aggressive endometrial cancer

Abstract Background: Strong risk factors for the most common (endometrioid) type of endometrial cancer (EC) include obesity and exposure to high estrogen levels. While EC has a favorable prognosis overall, one third of women present with advanced stage disease at diagnosis which has high recurrence and mortality rates. Given the estrogen-mediated etiology of EC, the current study focuses on the selective estrogen receptor modulator (SERM) 27-hydroxycholesterol (27HC) pathway. SERMs like 27HC can mimic estrogenic actions, and experimental work indicates 27HC exposure leads to continuous estrogenic stimulation and increases proliferation in the endometrium. Objective: to identify biomarkers for more aggressive disease, particularly markers present in early stages of carcinogenesis, to help guide decisions regarding treatment options. Methods: We conducted immunohistochemical staining on two tissue microarrays (TMAs) representing EC and its precursor endometrial intraepithelial neoplasia (EIN) tissues to measure protein levels of the enzymes that metabolize cholesterol into 27HC (CYP27A1) and 27HC into bile acids (CYP7B1), the receptors that bind 27HC (Estrogen Receptor [ER])-alpha, ER-beta as well as Liver Receptor X [LXR]-alpha and LXR-beta) and progesterone receptor (PR). We will use Fisher's exact test to evaluate 27HC associated biomarkers (categories split at the median) in relation to the presence of myometrial invasion (MI) and final diagnosis (EC or not) in the EIN TMA, and to assess clinico-pathologic factors including disease stage and grade in the EC TMA. Results: We created a new EIN TMA using formalin-fixed paraffin-embedded endometrial curettage or Pipelle endometrial biopsies from 144 EIN cases of diverse racial/ethnic backgrounds (Japanese, Hawaiian, White, Filipino and Asian/Pacific Islander) who were treated between 2007-16 in the Hawaii Pacific Health System. The EIN TMA contains both abnormal EIN tissues and neighboring benign/non-atypical tissues. In total, 50% of the EIN cases had no EC, 30% had cancer with no myometrial invasion (MI) and 20% had cancer with myometrial invasion. We are concurrently evaluating 27HC pathway markers in a TMA representing EC tumors from 96 cases who were treated in the same hospitals between 2001-07. The EC TMA represents diverse racial/ethnic groups including 28% Japanese American, 25% Native Hawaiian and 23% white cases (24% other). The EC TMA contains representative tissues from 91% endometrioid histotype cases and 72% localized and 28% regional/distant stage cases. We will examine associations between 27HC pathway biomarkers and clinico-pathologic characteristics of EC and EIN and will present our findings at the meeting. Conclusions: This study provides new data to determine whether 27HC pathway biomarkers may relate to characteristics of aggressive EC, such as the presence of myometrial invasion and higher stage and grade at diagnosis. Citation Format: Danja Sarink, Lenora W. Loo, Jeffrey Killeen, Brenda Y. Hernandez, Owen T. Chan, Melissa A. Merrit. Investigation of 27-hydroxycholesterol as a biomarker for aggressive endometrial cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3490.

Abstract 6426: Novel mechanism of PIM2 inhibition leads to significant effect on solid tumors

Abstract Background: PIM2 is overexpressed in hematopoietic and solid cancers, and is involved in multiple signaling pathways. In hematologic malignancies, PIM2 has been shown to be a pro-survival factor and demonstrated to be a possible therapeutic target. However, the role of PIM2 as a therapeutic target in solid cancers has not been fully elucidated. Methods: PIM2 expression was compared between normal and cancer tissues in The Cancer Genome Atlas (TCGA) datasets. Pan-PIM inhibitor treatment, as well as PIM2 overexpression/knockdown technique was utilized to investigate the PIM2 role in solid cancers. Multiple cancer models were utilized for in vitro and in vivo experiments to investigate if PIM2 as a therapeutic target and examine mechanism of anti-tumor activity by JP11646. Results: PIM2 was overexpressed in several types of cancer tissues, including breast, esophageal, head-neck, kidney, liver and endometrial cancers in TCGA. PIM2 overexpression promoted tumor growth in in vivo breast cancer mouse model. PIM2 inhibition by siRNA as well as pan-PIM inhibitor JP11646 activated apoptosis as seen by increased cleaved PARP. JP11646 treatment inhibited cancer cell proliferation in a dose-dependent manner in vitro in various types of solid cancers, including head-neck, ovarian, breast, prostate, liver, pancreatic, colorectal and non-small cell lung cancers. Interestingly, treatment with pan-PIM inhibitor JP11646 resulted in selective downregulation of PIM2 protein expression, but not PIM1 or PIM3 in breast cancer cell lines, BT549 and MDA-MB-231. The treatment also resulted in downregulation of phosphorylated downstream targets, 4EBP1 and TSC2 in breast cancer cells. However, additional proteasome inhibitor treatment blocked PIM2 downregulation and apoptosis activation was not seen. The result suggests that proteasome complex is required for PIM2 degradation which is necessary to induce apoptosis. JP11646 treatment inhibited tumor growth in breast, liver, pancreas, and non-small cell lung cancer in vivo xenograft models and was compared to multiple standard of care treatments showing advantage in lung tumors. Conclusion: We found that PIM2 promoted cancer progression in solid tumors. We show novel mechanism of JP11646 targeting PIM2 for degradation and induction of apoptosis. We show that PIM2 may serve as a novel therapeutic target for multiple types of solid cancers with enhanced therapeutic effect through protein degradation rather than kinase inhibition alone. Citation Format: Eriko Katsuta, Kazuaki Takabe, Alex Adjei, Mateusz Opyrchal. Novel mechanism of PIM2 inhibition leads to significant effect on solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6426.

Subdivision of IIIC Stage for Endometrioid Carcinoma to Better Predict Prognosis and Treatment Guidance

Objective: The prognostic value of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) IIIC staging in endometrioid carcinoma patients remains debatable. The current study aimed to compare the prognosis between IIIC1 and IIIC2 patients with endometrioid carcinoma and attempt to conduct a new subdivision.Methods: By using the Surveillance, Epidemiology, and End Results (SEER) database, patients with endometrioid-type endometrial cancer diagnosed from 2004 to 2015 were identified and randomly divided into training and validation sets. We developed a Fine–Gray competing risk model to compare the cancer-specific mortality (CSM). The IIIC subdivision system was built based on the independent prognostic factors. The cumulative incidence curves were compared using Gray's test or log-rank test. Nomogram for predicting 3- or 5-years CSM was constructed and subsequently validated internally and externally.Results: The IIIC subdivision defined by FIGO staging, including IIIC1 and IIIC2, exhibited no association with CSM in multivariate analysis [subdistribution hazard ratio [SHR] = 1.03, 95% CI [0.85–1.26], P = 0.760]. The IIIC category was subdivided into three subcategories based on the tumor (T) and nodes (N) stage, including IIICa (T1N1 and T1N2), IIICb (T2N1 and T2N2), and IIICc (T2N1 and T2N2). The prognosis across new IIIC subcategories with CSM remained significant [IIICb vs. IIICa: SHR = 1.53, 95% CI [1.18–1.98], P = 0.001; IIICc vs. IIICa: SHR = 2.64, 95% CI [2.13–3.28], P < 0.001]. Postoperative adjuvant chemotherapy or radiotherapy alone did not improve survival for patients categorized as IIICa or IIICb, and all IIIC patients benefited most from combination of postoperative chemotherapy and radiotherapy [IIICa: SHR = 0.59, 95% CI [0.43–0.82], P = 0.001; IIICb: SHR = 0.66, 95% CI [0.45–0.97], P = 0.036; IIICc: SHR = 0.44, 95% CI [0.34–0.58], P < 0.001]. A nomogram based on competing risk model was built to predict the long-term survival of IIIC patients, with a concordance index above 0.70 both in training and validation set.Conclusion: There was no prognostic difference between FIGO IIIC1 and IIIC2 patients with endometrioid-type endometrial cancer. A new subdivision of IIIC category facilitates prognosis prediction and treatment modalities. A combination of postoperative chemotherapy and radiotherapy exerted as the optimal choice for endometrioid cancer patients with IIIC stage.

Is the risk of substantial LVSI in stage I endometrial cancer similar to PORTEC in the North American population? – A single-institution study

ObjectivesA pooled analysis of PORTEC-1 & 2 identified substantial lymphovascular space invasion (LVSI) in 4.8% of patients, which predicted for pelvic recurrence, distant metastasis, and overall survival. Our institution implemented the PORTEC three-tier system of LVSI reporting (absent, focal, or substantial). We aimed to quantify the incidence of substantial LVSI in a North American population and to correlate extent of LVSI with lymph node (LN) involvement. MethodsA retrospective review was conducted on patients with clinically uterine-confined, endometrioid type endometrial cancer who underwent surgical staging and were found to have pT1a-b disease. Binary logistic regression was used to assess predictors of LN involvement (defined as ITC, micrometastases, or macrometastases). ResultsIn total, 438 patients with pT1a-b disease were identified. In the overall cohort and in the subset meeting PORTEC-1 inclusion criteria (n = 195), no LVSI was present in 67.4% and 50.8%; focal LVSI was present in 16.7% and 24.1%; and substantial LVSI was present in 16.0% and 25.1%, respectively. Among patients who underwent surgical LN assessment (79.2%, n = 347), LNs were involved in 3.3% without LVSI, 7.5% with focal LVSI (OR 2.4), and 15.2% with substantial LVSI (OR 5.3) (p = .005), with a similar trend in the PORTEC-1 cohort. Extent of LVSI correlated with disease burden in LN metastases. ConclusionOur incidence of substantial LVSI was three to five times higher than reported by PORTEC and correlated with LN involvement. This questions the reproducibility of the three-tier LVSI reporting system and emphasizes the need for multi-institutional data outside PORTEC for confirmation of our findings.

The role of histology on endometrial cancer survival disparities in diverse Florida.

BackgroundEndometrial cancer (EC) mortality is particularly high among non-Hispanic Blacks and is twice that of non-Hispanic Whites. However, comparisons of EC survival outcomes by race/ethnicity are often confounded by histology and grade. Here, we analyze EC survival disparities in multiracial Florida with a focus on EC types (1 and 2) and subtypes, defined according to histology and grade.MethodsAll 27,809 cases of EC diagnosed during 2005–2016 were obtained from the Florida Cancer Registry. Age-standardized, 5-year cause-specific survival by race/ethnicity and histological type were calculated. Fine and Gray competing risk regression was used to estimate sub-distribution hazard ratios (sHRs) for associations between risk of death due to EC and potential predictive factors such as histology/grade, age, stage at diagnosis, and insurance.ResultsType 2 EC accounted for only 38.7% of all incident EC-cases but 74.6% of all EC-deaths. Blacks were disproportionately affected by type 2 EC (57.6%) compared to Whites, Hispanics, and Asians (35.6%, 37.7%, and 43.0%, respectively). Age-adjusted 5-year survival for types 1 and 2 were 85.3% and 51.6%, respectively; however, there was wide variation within type 2 subtypes, ranging from 60.2% for mixed cell EC to as low as 30.1% for carcinosarcoma. In the multivariable model, Blacks with type 2 EC had a 23% higher risk of death due to EC (sHR: 1.23, 95%CI: 1.12–1.36) compared to Whites.ConclusionsPopulation-based analyses should consider the histological heterogeneity of EC because the less common type 2 EC drives racial/ethnic survival disparities in EC. Black women have a higher proportion of more aggressive histological types and an overall higher risk of death due to EC than Whites. To the extent that some of these histological types may be considered different diseases and require specific treatment approaches, further research on etiology and prognosis for detailed type 2 EC subtypes is warranted.

Understanding implementation success: protocol for an in-depth, mixed-methods process evaluation of a cluster randomised controlled trial testing methods to improve detection of Lynch syndrome in Australian hospitals

IntroductionIn multisite intervention trials, implementation success often varies widely across settings. Process evaluations are crucial to interpreting trial outcomes and understanding contextual factors and causal chains necessary for successful implementation....

The Role of Lymph-vascular Space Invasion towards Disease of Free Survival and Overall Survival Cancer in High-Risk Endometrial Cancer Endometrioid Type Patients

Major prognostic factors of endometrial cancer include stage, age, histopathological type, grading, depth of invasion of myometrium, and presence of Lymph-vascular Space Invasion (LVSI). This study evaluated the LVSI in disease free survival (DFS) and overall survival (OS) in high-risk endometrial cancer endometrioid type. This was a retrospective study. Survival analysis using Kaplan-Maier curve, log rank test, cox-regression and logistic regression were used to determine effects among variables. Among fifty-six patients, 43% of patients were <60 years, 73% with BMI <30, 17% were multiparous, and 79% were menopausal patients. There were 32% of patients with positive LVSI. Most clinical stages were found in stage III with 31 cases (55%). Patients with positive LVSI had OS lower than patients with negative LVSI (50% vs 55.3%). There were no significant results of LVSI as prognostic factor for OS. Patients with LVSI positive had survival time of 26.5 months (20.5 – 32.5). There were no significant results of LVSI as prognostic factor for DFS. Patients with positive LVSI had lower DFS than patients with negative LVSI (81.8% vs 85.7%). There were significant results of LVSI as prognostic factor for high-risk endometrioid type endometrial cancer with stage endometrial cancer with p = 0.01. LVSI acts as prognostic factor for high-risk endometrioid type endometrial cancer associated with stage endometrial cancer. However, there was no effect in DFS and OS.

Selection of Endogenous Control Reference Genes for Studies on Type 1 or Type 2 Endometrial Cancer

A panel of 32 candidate reference genes was used to identify the most stable genes for gene normalisation in quantitative RT-PCR studies using endometrial biopsies obtained from women with endometrial cancer (type 1 or type 2) and without cancer (controls). RNA from the biopsies was isolated, examined for purity and quality, and then reverse transcribed into cDNA before being subjected to real-time qRT-PCR analysis in triplicate within the TaqMan gene Expression Assay kit. The most ‘stable’ endogenous control genes were then identified using the geNorm qbase + 2 and NormFinder software packages. PSMC4, PUM1 and IPO8 were identified as the best reference genes combination for type 1 endometrial cancer (grades 1, 2 and 3), whereas for type 2 endometrial cancer (serous and carcinosarcoma), UBC, MRPL19, PGK1 and PPIA were the best reference genes combination. We conclude that the use of these normaliser combinations should provide accurate interpretation of gene expression at the transcript level in endometrial cancer studies especially for types 1 and 2 cancers.

SUN-133 Intratumoral Expression of Steroid Receptors, CD68+ Macrophages and Mdm2 in Different Molecular-Biological Types of Endometrial Cancer

Background and aims: In Risk Classifier for Endometrial Cancer/EC (ProMisE) 4 molecular biological types of this tumor are described recently [1,2,3] and need an additional research, including evaluation of hormone-associated characteristics of both tumor tissue and patients [4]. Aim of the work was a study of estrogen (ER) and progesterone (PR) receptors in comparison with CD68+ macrophage infiltration (which promotes the invasion of tumor cells into the myometrium [5]) and expression of MDM2 protein, a negative regulator of p53 [6], in EC types presented in the ProMisE classification. Materials and methods: The tumor tissue of 218 EC patients included in the study (mean age 60.6 years) was assigned according to the data of genetic and immunohistochemical analysis to the types of carcinomas with gene POLE mutations, deficiency of mismatch repair proteins (MMR-D), expression (positive or diffuse) of p53 oncoprotein and to the type without characteristic molecular profile, WCMP. Immunohistochemistry was used also for evaluation of ER (Ventana antibodies, clone SP1) and PR (Ventana antibodies, clone 1E2) according to Allred, MDM2 (antibodies ABCAM, dilution 1:200) and macrophage marker CD68 (DAKO antibodies, clone CD8/144B). Results: According to the averaged data, the highest expression of ER and PR was found in EC types MMR-D and WCMP, and the lowest, respectively, in types POLE and p53+. Most often, positive expression of MDM2 (in 93.2% and 96.9% of studied cases) was detected respectively in MMR-D and p53+ type of EC, indicating, therefore, a positive relationship between MDM2 and the presence of steroid receptors in the first of these types (MMR-D) and negative - in the second of them (p53+). Expression of CD68+ macrophages demonstrated (contrary to the EC types POLE and p53+) a tendency to the lower values in types MMR-D and WCMP (128.0 ± 8.1 and 113.5 ± 6.3 cond.un.), i.e. in tumors with potential sensitivity to estrogen. Conclusions: The results indicate the importance of taking into account of both - the molecular biological type of the EC as well as the role of microenvironment of tumor cells, including the colonization of the neoplasm’ tissue by macrophages (and possibly lymphocytes) and the features of hormonal signal transmission in it. For further analysis, it is desirable to consider also the EC histotype, as one of the factors underlying various prognostic groups of this tumor [7].

Computational analysis for identification of the extracellular matrix molecules involved in endometrial cancer progression.

Recurrence and poorly differentiated (grade 3 and above) and atypical cell type endometrial cancer (EC) have poor prognosis outcome. The mechanisms and characteristics of recurrence and distal metastasis of EC remain unclear. The extracellular matrix (ECM) of the reproductive tract in women undergoes extensive structural remodelling changes every month. Altered ECMs surrounding cells were believed to play crucial roles in a cancer progression. To decipher the associations between ECM and EC development, we generated a PAN-ECM Data list of 1516 genes including ECM molecules (ECMs), synthetic and degradation enzymes for ECMs, ECM receptors, and soluble molecules that regulate ECM and used RNA-Seq data from The Cancer Genome Atlas (TCGA) for the studies. The alterations of PAN-ECM genes by comparing the RNA-Seq expressions profiles of EC samples which have been grouped as tumorigenesis and metastasis group based on their pathological grading were identified. Differential analyses including functional enrichment, co-expression network, and molecular network analysis were carried out to identify the specific PAN-ECM genes that may involve in the progression of EC. Eight hundred and thirty-one and 241 PAN-ECM genes were significantly involved in tumorigenesis (p-value <1.571e-15) and metastasis (p-value <2.2e-16), respectively, whereas 140 genes were in the intersection of tumorigenesis and metastasis. Interestingly, 92 of the 140 intersecting PAN-ECM genes showed contrasting fold changes between the tumorigenesis and metastasis datasets. Enrichment analysis for the contrast PAN-ECM genes indicated pathways such as GP6 signaling, ILK signaling, and interleukin (IL)-8 signaling pathways were activated in metastasis but inhibited in tumorigenesis. The significantly activated ECM and ECM associated genes in GP6 signaling, ILK signaling, and interleukin (IL)-8 signaling pathways may play crucial roles in metastasis of EC. Our study provides a better understanding of the etiology and the progression of EC.

Evaluation of Serum Human Epididymis Secretory Protein 4 (HE4) in Benign Endometrial Disease and Endometrial Cancer

Abstract Objective The incidence of endometrial cancer is constantly growing. More aggressive types of endometrial cancer as well as the incidence in younger women are being observed. More than 80% of cases are diagnosed in early stages due to early symptoms like abnormal bleeding. Aim of our study to evaluate the ability of serum HE4 concentration to differentiate between benign endometrial disease and endometrial cancer and ass’s correlation it with prognosis of EC. Material and methods Serum HE4 level was measured in 85 patients with abnormal uterine bleeding. Based on histology after curettage the study group was divided into the benign and malignant endometrial pathology groups. Statistical analysis was performed using Mann-Whitney test Results The difference of serum HE4 level between benign endometrial pathology and cancer was significant (p = 0.000) and the cut-off for identification of patients with endometrial cancer was 62 pmol/l. There was a significant difference between Stage (I – II) endometrial cancer, and Stage (III – IV) p = 0.01, Patients who needed lymphadenectomy had significantly higher HE4 level than those who had no indications for this procedure (p = 0,001). Conclusion HE4 is a useful biomarker in diagnosing endometrial cancer. HE4 is associated with high grade endometrial cancer. It can also serve as an useful preoperative counseling tool to identify patients, who may require pelvic lymphadenectomy.

STEROID RECEPTOR PHENOTYPE, EXPRESSION OF HER-2/NEU, PD-1, PD-L1 AND LYMPHOCYTIC-MACROPHAGAL INFILTRATION OF ENDOMETRIAL CARCINOMAS: COMPARISON OF MODERN MOLECULAR BIOLOGICAL TYPES OF THE DISEASE (THE ROLE OF BODY MASS INDEX)

The aim of this study was to evaluate steroid receptors’ status of tumor tissue in different molecular biological types of endometrial cancer (EC), subdivided according to the current classification, and their colonization by lymphocytic and macrophage cells, taking into account body mass index of the patients. Materials and methods: Material from treatment-naive patients with EC (total n = 229) was included; the number of sick persons varied depending on the method used. The average age of patients was close to 60 years, and about 90% of them were postmenopausal. It was possible to divide the results of the work into two main subgroups: a) depending on the molecular biological type of the tumor (determined on the basis of genetic and immunohistochemical analysis), and b) depending on the value of the body mass index (BMI). The latter approach was used in patients with EC type demonstrating a defective mismatch repair of the incorrectly paired nucleotides (MMR-D) and with a type without characteristic molecular profile signs (WCMP), but was not applied (due to the smaller number of patients) in EC types with a POLE gene mutation or with expression of the oncoprotein p53. According to the data obtained, when comparing various types of EC, the lowest values of Allred ER and PR scores were revealed for POLE-mutant and p53 types, while the “triple-negative” variant of the tumor (ER-, PR-, HER2/neu-) was most common in POLE-mutant (45.5% of cases) and WCMP (19.4%) types of EC. The p53+ type of EC is characterized by inclination to the higher expression of the macrophage marker CD68 and lymphocytic Foxp3, as well as mRNA of PD-1 and SALL4. In addition to the said above, for WCMP type of EC is peculiar, on the contrary, a decrease in the expression of lymphocytic markers CD8 (protein) and PD-L1 (mRNA). When assessing the role of BMI, its value of &gt;30.0 (characteristic for obesity) was combined with an inclination to the increase of HER-2/neu expression in the case of MMR-D EC type and to the decrease of HER-2 /neu, FOXp3 and ER expression in WCMP type. Conclusions: The accumulated information (mainly describing here hormonal sensitivity of the tumor tissue and its lymphocytic-macrophage infiltration) additionally confirms our earlier expressed opinion that the differences between women with EC are determined by both the affiliation of the neoplasm to one or another molecular biological type (subdivided according to the contemporary classification), as well as by body mass value and (very likely) the associated hormonal and metabolic attributes.

P-53 expression in complex and/or atypical endometrial hyperplasia and endometrial adenocarcinoma

Endometrial cancer holds fourth position after breast, colon and lung cancers. In different parts of the world endometrial carcinoma accounts for 4-8% of all cancers. The Age Standardised Rate (ASR) is approximately 4.3 cases per 1,00,000 women. Endometrial cancers are majorly observed in post menopausal women. The age group for diagnosis of endometrial cancers is around 60 years. The most common symptom in patients of endometrial carcinoma is postmenopausal bleeding. The prominent risk factors for endometrial carcinoma include obesity, nulliparity, early menarche and late menopause, and estrogen therapy. There are two types of endometrial cancers: type I endometrial cancer is associated with unopposed estrogen expression and is more common (80% of cases) whereas type II endometrial malignancies are not related to estrogen and are more aggressive tumor.P53-driven model of carcinogenesis is responsible for the rapid development and progression of type II endometrial lesions. Early stage tumors (low grade) are primarily estrogen and progesterone receptor positive and P-53 negative. In contrast the advanced stage tumors (high grade) tumors show strong positive expression for P-53 and are negative for estrogen and progesterone receptors.

Concordance of preoperative and postoperative histological grades in endometrioid type endometrial cancer

Concordance of preoperative and postoperative histological grades in endometrioid type endometrial cancer

The Role of Insulin, IGF-1 and PRAS40 in the Processes of Oncogenesis in Women with Type 2 Diabetes Mellitus and Endometrial Cancer

The objective of the research was to investigate the content of insulin, insulin-like growth factor-1 and phosphorylated protein kinase proline-rich Akt substrate of 40kDa and to determine their role in the activation of oncogenesis processes in women with type 2 diabetes mellitus and endometrial cancer.&#x0D; Materials and methods. There were examined 46 women who were divided into 4 groups: Group I included healthy women; Group II comprised women with type 2 diabetes mellitus; Group III included women with endometrial cancer; Group IV comprised women with endometrial cancer and co-existent type 2 diabetes mellitus. The levels of insulin, insulin-like growth factor-1, phospho- proline-rich Akt substrate of 40kDa were determined by immune-enzyme analysis. The compensation of diabetes mellitus was evaluated by hemoglobin A1c level using method of ion-exchange chromatography. The results obtained were analyzed using statistical analysis.&#x0D; Results. Women of all study groups had increased levels of insulin and insulin-like growth factor-1 as compared to the control group (p&lt;0.05). The level of phospho-proline-rich Akt substrate of 40kDa increased in the patients of Group II (p&lt;0.05) and the patients of Group III (p&lt;0.05) and decreased in the patients of Group IV (p&lt;0.05). According to correlation analysis, phospho-proline-rich Akt substrate of 40kDa was found to correlate with body mass index, insulin and insulin-like growth factor-1 in Group II, body mass index and insulin-like growth factor-1 in Group III and body mass index in Group IV (p&lt;0.05).&#x0D; Conclusions. There was found an association between type 2 diabetes mellitus and endometrial cancer through obesity, hyperinsulinemia and insulin-like growth factor-1. The increase in phospho- proline-rich Akt substrate of 40kDa level was a sign of activation of mTOR and oncogenesis processes in the patients with type 2 diabetes mellitus. The decrease in phospho-proline-rich Akt substrate of 40kDa in the patients with endometrial cancer and co-existent type 2 diabetes mellitus can be explained by the influence of other intracellular regulatory systems or the effects of antidiabetic drugs, that requires additional study.

Factors predicting recurrence in patients with stage IA endometrioid endometrial cancer: what is the importance of LVSI?

The aim of this study is to define the clinical and pathological prognostic factors for recurrence and to evaluate the recurrence patterns and adjuvant therapies used in this group of patients with stage IA endometrioid type endometrial cancer (FIGO 2009-International Federation of Gynecology and Obstetrics). Among the patients with epithelial endometrial cancer operated between January 1993 and May 2013 in a single institution, 720 patients with stage IA endometrioid endometrial cancer were included. Patients with a tumor type of serous, clear cell, mucinous, undifferentiated, and mixed type and with a tumor containing sarcomatous component and the patients with a secondary primer cancer were excluded from the study. Lympho-vascular space invasion (LVSI) was present in 60 (8.3%) patients. Pelvic and para-aortic lymphadenectomy was performed in 266 (36.9%) patients. Median follow-up time was 48 months (range 3-240). Recurrence occurred in 23 (3.4%) patients and 6 (0.9%) died of disease. The median time-to recurrence (TTR) was 24 months (range 4-52 months) in the patients with recurrence. LVSI was associated with recurrence in the univariate analysis. Five-year disease-free survival (DFS) decreased from 96.8 to 80.1% in the presence of LVSI (p < 0.001). This association could not be shown in patients who had had lymphadenectomy (p = 0.136). Extra-pelvic recurrence occurred in 6.7% and 1% of the patients with and without LVSI, respectively, (p = 0.001). Any independent prognostic factor could not be detected in the multivariate analysis. Only LVSI and tumor grade were associated with DFS and disease-specific survival (DSS), respectively, in the 686 patients with stage IA endometrial cancer in the univariate analysis, since these associations could not be shown in multivariate analysis.