Extent Of Myometrial Invasion Research Articles

Expression of Programmed Cell Death Ligand-1 and Mismatch Repair Status in Endometrial Carcinomas.

Programmed death ligand-1 (PD-L1) is a co-regulatory molecule that suppresses local immunity, and mismatch repair (MMR) deficiency (dMMR) is reported to influence the response to anti-PD-L1-targeted therapy. This study was conducted to find the PD-L1 status, the occurrence of dMMR in endometrial carcinomas, and the association between them. The study included 35 resected specimens of endometrial carcinomas represented on formalin-fixed paraffin-embedded sections from January 2016 to July 2020. The clinicopathologic information including patient age, tumor histologic type, grade, stage, lymphovascular invasion, the extent of myometrial invasion, and the percentage of tumor-infiltrating lymphocytes (TILs) were obtained in all cases. The expression of PD-L1 and MMR antibodies including mutS homolog 2 (MSH-2), MSH-6, mutL homolog 1 (MLH-1) and MLH-3, and postmeiotic segregation 2 were assessed using immunohistochemistry. The statistical analysis was done using the Statistical Package for the Social Sciences (SPSS) version 26. PD-L1 expression was noted in 48.6% of the cases in tumor cells and 65.7% of the cases in TILs and MMR was deficient in 28.6% of endometrial carcinomas. A statistically significant relation was noted between dMMR and TILs, PD-L1 expression in tumor cells and TILs, PD-L1 expression in tumor cells, and extent of myometrial invasion. Although there was no statistically significant association between MMR status and PD-L1 expression in tumor cells or TILs, 60% of patients with dMMR were PD-L1 positive. Sixty percent of dMMR cases showed PD-L1 expression in tumor cells. We conclude, ECs that are MMR deficient might get better response to anti-PD-L1 therapy. This study also revealed the prognostic use of TILs in PD-L1-expressed tumors.

RON, ROR1 and SUSD2 expression in tissues of endometrial carcinoma patients. Clinicopathological and prognostic implications.

IntroductionEndometrial carcinoma is now considered a common female gynecologic cancer with increasing incidence, with 13–25% of patients being still liable to recurrence and metastasis, which needs further studies to detect novel targets and new therapies. The aim of the study was evaluate tissue expression of RON, ROR1 and SUSD2 in endometrial carcinoma and atypical endometrial hyperplasia using immunohistochemistry and correlate their expression with clinical, pathological and prognostic parameters of patients.Material and methodsWe included samples from 100 patients with endometrial carcinoma. Sections from paraffin blocks were stained with RON, ROR1 and SUSD2 using immunohistochemistry. Correlations between marker expression, clinicopathological features and prognostic samples were evaluated.ResultsUpregulation of RON and ROR1 and downregulation of SUSD2 expression were found in endometrial carcinoma more than atypical endometrial hyperplasia (p < 0.001). High RON and ROR1 expression levels were significantly associated with high grade (p < 0.001), presence of lymph node metastases (p = 0.003), distant metastases (p = 0.009), advanced International Federation of Gynecology and Obstetrics stage (p = 0.002), poor response to therapy (p = 0.046), and lower recurrence-free survival (RFS) rate (p = 0.002), progression-free survival (PFS) rate (p = 0.008), distant metastasis-free survival (DMFS) rate (p = 0.019) and overall survival rate (p < 0.001). Low SUSD2 expression was significantly associated with older patient age (p = 0.002), large tumor size (p = 0.003), high grade (p = 0.005), presence of adnexal invasion (p = 0.023), presence of lympho-vascular invasion (p = 0.021), extent of myometrial invasion (p = 0.002), lower RFS rate (p = 0.008), lower PFS rate (p = 0.023), and lower DMFS rate (p < 0.001).ConclusionsUpregulation of RON and ROR1 and downregulation of SUSD2 lead to promotion of endometrial cancer cell proliferation, migration, epithelial-mesenchymal transition, and invasion.

VP66.02: 3D ultrasound for preoperatively staging endometrial cancer

An article was recently published in Obstetrics and Gynecology, comparing available strategies to determine the optimal methodology to employ when deciding on whether to perform a pelvic lymphadenectomy (PL) in conjunction with a hysterectomy for the treatment of Endometrial Carcinoma (EC). Though this investigation was published a few years ago (the citation is listed below), the case series was continued to the present day. All patients in this investigation who were clinically diagnosed with EC were examined sonographically prior to scheduled surgery, using 3DTVS and power Doppler angiography (PDA), and Virtual Organ Computer-Aided Analysis (VOCAL) and Volume Contrast Imaging (VCI) from April, 2015 through March, 2020. All patients underwent a subsequent surgical procedure with the resulting surgical histology obtained within three months after the TVS, to be compared with those pre-operative ultrasound findings. Deep myometrial infiltration was diagnosed when the tumour was equal or more than 50% of the total thickness of the uterine wall. The identified sonographic features of the patients enrolled in this study were compared with the intraoperative and post-operative pathologic findings. With the results of the analysis of 27 patients, the sonographic findings predicted the minimum EC staging 100 % of the time. There may be some benefit to knowing the extent of myometrial invasion at the time of hysterectomy, so as to best decide on whether to perform a PL. In this case series, the authors correctly predicted the pathologic EC staging 100% of the time with pre-operative 3DTVS, which should be strongly considered for its routine pre-surgical use when the diagnosis of EC is being considered. REFERENCE 1. Fernandez CM, Levine EM, Dini M, Bannon K, Butler S, LocherS: Predictive value of three-dimensional transvaginal sonographyfor staging of endometrial carcinoma. J Diagn Med Sonogr2018; 34(5): 496-500.

Evaluation of prevalence and prognostic significance of human epidermal growth factor receptor 2/neu expression in carcinoma endometrium

Context: Endometrial cancer is a frequently encountered gynecological malignancy. An adverse prognostic immunohistochemical marker had not been identified until recently. Recent studies have used human epidermal growth factor receptor 2 (HER2)/neu expression as a marker for adverse outcomes in carcinoma endometrium, as proven in carcinoma breast. Aim: The present study was undertaken to correlate HER2/neu expression with prognostic factors in cases of endometrial carcinoma. Materials and Methods: This was a prospective study on evaluation of HER2/neu expression done on 30 patients with biopsy-proven carcinoma endometrium admitted in the hospital for staging laparotomy. Histopathological examination was performed and HER2/neu expression was assessed by immunohistochemistry and was categorized into (1) Group 1: HER2/neu 0/1+ (negative), (2) Group 2: HER2/neu 2+ (equivocal), and (3) Group 3: HER2/neu 3+ (positive). All the cases were followed up for a period of 1 year. Statistical Analysis: All data analyses were carried out using statistical software SPSS, IBM version 21.0. P&lt; 0.05 was considered as significant. Results: 0/1+ HER2/neu expression (negative) was detected in 19 patients (63.33%), 2+ HER2/neu expression (equivocal) was detected in 4 patients (13.33%), and 3+ HER2/neu expression (positive) was detected in 7 patients (23.33%). HER2/neu 3+ group was significantly associated with non-endometrioid histology (P = 0.003) and high tumor grade (P = 0.005). The association of HER2/neu 3+ group with advanced disease and lymph node involvement showed a trend, but it was not statistically significant. No association was found between HER2/neu overexpression and extent of myometrial invasion. There were two recurrences in 1 year follow-up period. HER2/ neu expression (2+ and 3+) was seen the recurrence cases. Conclusion: HER2/neu overexpression was found to be an adverse prognostic marker in carcinoma endometrium, which could form the basis of targeted chemotherapy.

Expression of CD44 variant 6 and its prognostic value in benign and malignant endometrial tissue.

CD44 expression in both the early and metastatic phases of many epithelial and non-epithelial cancers is strongly prognostic. The objective of the study is to evaluate whether there is any relationship between the expression of CDD44v6 and endometrial cancer (EC) staging and prognosis. This retrospective study included 60 EC patients for whom surgical staging was performed between 2000 and 2006. Twenty-eight randomly selected patients with normal endometria served as the control group. We immunohistochemically evaluated membranous and cytoplasmic CD44v6 staining in tissue paraffin blocks. The results were graded as positive or negative. Membranous staining in both advanced and early stage EC patients was significantly higher than that in the control group (p=0.002). The extent of either membranous or cytoplasmic staining in both advanced- and early stage patients did not differ significantly by age, tumor grade, stage, extent of myometrial invasion, lymph node involvement, cytology, adnexal involvement, or omental spreading. In advanced-stage patients, neither papillary serous not clear cell cancers exhibited cytoplasmic staining. CD44v6 membranous staining can be useful for differentiating malignant from benign endometrial tissue. However, staining is not associated with EC staging or prognosis.

DNA ploidy may be a prognostic marker in stage I and II serous adenocarcinoma of the endometrium

In patients with serous adenocarcinoma (SAC) of the endometrium, we evaluated the prognostic importance of clinicopathological parameters, DNA ploidy, and immunoexpression of p53, estrogen receptor (ER), progesterone receptor (PR), and Ki-67. In a series of 73 stage I and II SAC, DNA ploidy analysis was performed on hysterectomy specimens using DNA image cytometry. Immunohistochemical analysis of p53, ER, PR, and Ki-67 expression was additionally performed. In the review of the histological slides by three gynecologic pathologists, the presence of a serous component was not agreed upon in 17 (23 %) cases. The remaining 56 cases, consisting of pure SAC or SAC mixed with endometrioid adenocarcinoma, were further analyzed. Tumor recurrence was observed in 14 patients, and 28 patients died during the follow-up period. Patients with diploid (n = 19), aneuploid (n = 29), and tetraploid (n = 8) tumor had 5-year recurrence rates of 10, 38, and 53 %, respectively (p = 0.09). A DNA ploidy parameter, 5c exceeding rate, was found to be a prognostic marker for recurrence (p = 0.03), progression-free survival (p < 0.01), and overall survival (p = 0.02). Immunoexpression of p53, ER, PR, and Ki-67 did not have prognostic value, and the same was true for FIGO stage, lymphovascular invasion, the extent of myometrial invasion, and lymphadenectomy. The histological diagnosis of SAC may be difficult in some cases. Established clinicopathological parameters do not seem to be strong prognosticators in stage I and II disease. A DNA ploidy parameter, 5c exceeding rate, may be a prognostic marker in this patient group and should be further validated in larger series.

Uterine adenosarcoma with ovarian sex cord-like differentiation: A case report and review of the literature

Objectives To determine the prognosis of uterine adenosarcoma with ovarian sex cord like-differentiation after treatment and to review the literature. Case Report A 47-year-old premenopausal unmarried woman presented with irregular menstrual bleeding and uterine mass. Sonographic examination, suggested two uterine fibroids located in the uterine fundus and cervix measuring 4 × 3 cm and 3 × 3 cm, respectively. Total abdominal hysterectomy with bilateral salpingo-oopherectomy was performed and the histopathology report confirmed the diagnosis of uterine adenosarcoma with ovarian sex cord like-differentiation. The patient received neither chemotherapy nor other adjuvant therapy because the tumor had low malignant potential, and the extent of myometrial invasion was less than half of the whole myometrium. The patient had an uneventful recovery, and no recurrence was detected for 2 years in the follow-up period. Conclusion Uterine adenosarcomas mostly have relatively low malignant potential. Surgery is the optimal standard treatment for patients. Although there is not enough data in the present literature, benign epithelial differentiations, such as sex cord-like elements may reflect the behaviour of the tumour and shows the tendency to have a benign course in most of cases.

Commentary on: Staging of endometrial carcinomas with MRI using traditional and novel MRI techniques

In their review, Haldorsen and Salvesen1 discuss the role of magnetic resonance imaging (MRI) in the staging of endometrial cancer. They present an evaluation of the published evidence and compare the accuracy, sensitivity, and specificity of the MRI information with the reference standard postoperative pathological assessment. Although MRI (particularly contrast-enhanced MRI) performs well in assessing the depth and extent of myometrial invasion, it appears to be less sensitive in identifying cervical involvement and the presence of metastatic lymph nodes.

Prognostic significance and treatment implications of positive peritoneal cytology in endometrial adenocarcinoma: Unraveling a mystery

ObjectiveReview the literature on positive peritoneal cytology in endometrioid endometrial adenocarcinoma, its prognostic value, proposed treatment strategies, and future avenues of investigation. MethodsPubMed search of articles pertaining to stage IIIA endometrioid endometrial adenocarcinoma identified over 50 articles that were reviewed. Low-risk stage IIIA1 was defined as those with grade 1 or 2 disease, no evidence of cervical involvement, myometrial invasion less than 50% and no lymph vascular space invasion (LVSI). Analysis of available data was completed with weighted averages, Student's-t-test and Chi square statistical analyses. ResultsIncidence of positive washings is approximately 11%. In low-risk stage IIIA1 endometrial carcinoma patients, the rate of recurrence is 4.1%. In contrast, in high-risk stage IIIA1 endometrial carcinoma patients the rate of recurrence is 32%, a statistically significant difference (p <0.001). Positive peritoneal cytology is associated with an increased incidence of extrauterine disease but is not consistently linked to other high-risk factors such as positive lymph node status, extent of myometrial invasion or LVSI. ConclusionsTo date there is no definitive consensus on the prognostic significance of positive peritoneal cytology alone. However, even in the low-risk cohort with stage IIIA1 some patients will recur. Adjuvant therapy for low-risk stage IIIA diseased may or may not be of benefit. High-risk disease should be treated with chemotherapy, radiation or a combination thereof. A prospective, multicenter trial of comprehensively surgically staged patients with stage IIIA endometrial cancer is indicated in order to clearly define prognosis and treatment for these patients.

Extent of cervical involvement in endometrial cancer as a predictor of outcome

e16566 Background: Endometrial cancer will affect 40,000 women this year. Extent of myometrial invasion and presence of cervical stromal disease are risk-factors for metastasis and recurrence. Uterine cervical involvement is often not known in advance of surgery, and superficial involvement may not be seen at frozen section. The objective of this study was to determine if the extent of cervical invasion is a predictor of outcome. Methods: The institutional cancer registry was searched for cases of stage II uterine cancer from 1996–2006. Inclusion criteria were endometrioid histology and clinical data and pathology available for evaluation. Demographics, extent of surgery, tumor grade, depth of myometrial invasion, presence of lymph-vascular space invasion (LVSI), and last follow up were collected. In addition, a gynecologic pathologist evaluated all slides to determine depth of cervical stromal invasion. Statistical analysis to compare predictors of outcome was performed. Results: There were 800 cases of endometrial cancer diagnosed from 1996–2006, 75 (9%) were stage II. Fifty two cases met all inclusion criteria. Mean age at diagnosis was 63.4 years. Mean BMI was 31.6. Ninety four percent were white, 4% black, and 2% Asian. All patients had a hysterectomy, 6 (11.5%) had a radical hysterectomy and 36 (69%) had lymphadenectomy performed. Eighteen (34.6%) were stage IIA and 32 (61.5%) were IIB. LVSI was seen in 15 (28.8%) cases. On pathologic review, 37.5% had no cervical stromal invasion, 42.5% had invasion of less than half and 20% had invasion of more than half of the cervical stroma. Forty patients (77%) received adjuvant radiation. There were 8 recurrences and 6 disease-related deaths. The mean follow up period was 30 months. Extent of cervical invasion did not correlate with recurrence or survival. Factors associated with increased risk of recurrence were: LVSI (p = 0.017), lack of lymph node sampling (p = 0.035), and age &gt;55 years (p = 0.027). Women with and without recurrence were compared and did not significantly differ. Conclusions: In this study with pathologic review, extent of cervical involvement in stage II endometrial cancer was not associated with increased risk of recurrence or death. Age &gt;55 years, lack of node sampling and presence of LVSI were predictors of recurrent disease. No significant financial relationships to disclose.

Promoter Methylation and Differential Expression of π-Class Glutathione S-Transferase in Endometrial Carcinoma

Pi-class glutathione S-transferase (GSTP1), located on chromosome 11q13, codes for a phase II metabolic enzyme that detoxifies reactive electrophilic intermediates. The protein also interacts with steroid hormones in the human body. The role of GSTP1 in endometrial carcinoma has not been reported. In this study, we aimed at determining the expression of GSTP1 in relation to the epigenetic and genetic changes of the gene in endometrial carcinoma. The GSTP1 protein and mRNA expression was assessed by immunohistochemistry on tissue microarray and quantitative real-time reverse transcriptase-polymerase chain reaction, respectively. Its methylation status was studied by methylation-specific polymerase chain reaction and bisulfite sequencing. Possible mutations in coding region of GSTP1 were assessed by cDNA sequencing. Ninety-seven cases of endometrial carcinoma with available tissue blocks and clinical data were studied. Our results showed that 68.0% (66 of 97) of the cases showed reduced protein expression while 64% (16 of 25) showed reduced mRNA expression; 30.9% (30 of 97) of the cases demonstrated methylated alleles in at least one of the six methylation-specific polymerase chain reaction reactions. The methylation status significantly correlated with reduced protein expression (P = 0.008) and reduced mRNA expression (P = 0.003). Methylation at non-CpG sites including CpCpG trinucleotides and CpT dinucleotides were also observed. cDNA sequencing did not reveal genetic alterations in coding region of the gene. The extent of myometrial invasion was found to be significantly correlated with both the methylation status (P = 0.009) and the protein expression (P = 0.036) of the GSTP1 gene. We postulated that hypermethylation of the GSTP1 gene promoter region may act as a dynamic regulation mechanism contributing to reduced GSTP1 expression, which is associated with myometrial invasion potential of the endometrial carcinoma.

IMPROVING THE DIAGNOSIS AND MANAGEMENT OF FETAL GROWTH RESTRICTION: THE RATIONALE FOR A PLACENTA CLINIC

Successful pregnancy outcome depends on a co-coordinated series of events in development designed to attain normal placental function. The critical importance of placental vascular development is appreciated when a wide range of pregnancy complications including preterm labour (PTL), preterm premature rupture of the membranes (PPROM), pre-eclampsia (PE), fetal growth restriction (FGR), fetal demise (FD), and abruptio placenta (ABR) are all associated with restricted maternal and/or fetal blood flow, and secondary pathological lesions in the placental parenchyma. Other developmental defects of the placenta, such as its site (placenta praevia), extent of myometrial invasion (placenta accreta) or cord insertion (vasa praevia), may have major detrimental maternal and/or fetal effects if unrecognized during the antenatal period. In January 1999 we commenced a “Placenta Clinic” within the Fetal Medicine Unit at Mount Sinai Hospital (Toronto, Canada). Our rationale was that the early identification of many of these problems may, by facilitating appropriate multidisciplinary care and an elective delivery plan, reduce the attendant risks of maternal and perinatal morbidity and/or mortality due to placental malfunction.

Association between RCAS1 expression and clinical outcome in uterine endometrial cancer.

RCAS1, which acts as a ligand for a putative receptor on immune cells such as peripheral lymphocytes and natural killer cells, is strongly expressed in human cancers. RCAS1 can induce these cells to undergo apoptotic cell death, which suggests that RCAS1 expression may prohibit the stromal reaction occurring in a tumour. To clarify the clinical significance of RCAS1 expression in uterine endometrial cancer, we analysed the association between RCAS1 expression and clinicopathologic variables by statistical methods. With the use of immunohistochemical techniques, we performed a retrospective study of RCAS1 expression in resected tumour tissue from 147 patients with uterine endometrial cancer. We evaluated the statistical correlation between RCAS1 expression and clinicopathologic variables. RCAS1 was expressed in 106 of 147 patients with uterine endometrial cancer ; 30 of these 147 patients showed RCAS1 overexpression. Overexpression of RCAS1 was significantly correlated with age at surgery, stage, extent of myometrial invasion, and positive peritoneal cytologic results. Multivariate analysis revealed that RCAS1 expression and metastasis were clinically significant prognostic factors for the overall survival. These findings indicated that analysis for RCAS1 expression can provide crucial information about the clinical behaviour of uterine endometrial cancer, which may be valuable for the management of patients with this disease.

Assessment of the Depth and Extent of Myometrial Invasion in Uterine Adenomyosis Using MRI

Purpose: To determine the detection rate of MRI in the diagnosis of adenomyosis and ascertain the accuracy of MRI in assessing the extent and depth of the myometrial invasion. Materials and Methods: By retrospective analysis of MR images of the pelvis in 65 pathologically proven cases of uterine adenomyosis, we investigated the detection rate and differences of in the detection rate when this was based on (a) the extent, and (b) the depth of myometrial invasion. The condition was classified as diffuse or focal according to the extent of invasion, and mild, moderate, or severe according to its depth. Results: Pathologically, there were 35 cases of focal adenomyosis (53.8%), and 30 of diffuse adenomyosis (46.2%). Among patients with the focal variety of this condition, 12 cases were mild, 14 were mild, 14 were moderate, and nine were severe, while among those with the diffuse variety, two were mild, ten were moderate and 18 were severe. A total of 48 cases (73.8 the detection rate of focal adenomyosis was 60.0% (21/35) and that of diffuse adenomyosis was 90.0% (27/30). The detection rates of mild, moderate, and severe adenomyosis were 42.9%(6/14), 79.2%(19/24), and 85.2% (23/27), respectively. Among the 48 cases detected on MR images, the pathologic and MR findings were consistent with regard to both the extent and depth of myometrial invasion in 26(54.2%). For diffuse adenomyosis, the consistency rate was higher than for the focal variety (81.5 compared with 19%, 4/21). The extent of myometrial invasion was correctly evaluated in 32 cases (66.7 the consistency rate for the diffuse form was higher than for the focal form [96.3% (26/27), compared with 28.6% (6/21)]. In 42 cases (87.5%), the depth of invasion was correctly evaluated, though differences in this depth were not significant. Conclusion: MR imaging was a useful imaging modality in the diagnosis of uterine adenomyosis. With regard to the extant of mymetrial invasion, the detection rate was higher among cases of the diffuse form than of the focal form, and with regard to depth, the rate was higher among moderate and severe cases than among mild ones. These findings may be useful for preoperative diagnosis based on clinical symptoms, and provide important yardstick for decisions as to whether hysterectony should be replaced by an alternative therapy.

Altered tenascin expression during spontaneous endometrial carcinogenesis in the bdii/han rat

The BDII/Han rat develops spontaneous endometrial adenocarcinoma, which appears virtually identical histologically to human endometrial adenocarcinoma. The incidence rate of cancer formation in the rat is 90% and the mean lifetime of the animals is 22 months. This animal model therefore, is useful in the study of molecular aspects of spontaneous transformation as well as mammalian neoplastic progression. In this study we address the in-situ expression of tenascin, an extracellular matrix glycoprotein, during normal cyclic growth, during development of proliferative states, and during malignant transformation of the endometrium. Trace amounts of immunocytochemically detectable tenascin were found in 10% of young BDII/Han rats with a normal estrus cycle. In these inbred animals no tenascin was detectable in uteri without neoplastic progressive alterations of the endometrium. Tenascin immunoreactivity first appeared during proliferation in one of three uteri with cystic glandular hyperplasia. Prominent tenascin expression was detectable in all adenomatous hyperplasia, but restricted to the stromal mesenchyme, that surrounded the glands. In all endometrial adenocarcinomas tested, essentially the entire extracellular space of the stromal mesenchyme was immunoreactive with anti-tenascin antibodies while the epithelial glands themselves were negative. This staining pattern was observed independent of the degree of tumor differentiation or extent of myometrial invasion. The tenascin staining pattern was not significantly altered in tumors transplanted into the soft tissues of the neck of female BDII/Han rats. From our studies we conclude that tenascin may be a marker for the early detection of proliferative endometrial states.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic features of endometrial cancer in estrogen users and obese women

In a case-control study to evaluate risk factors for endometrial cancer in Italy, use of noncontraceptive estrogens was associated with a moderately increased risk, whereas obesity appeared to be the most important single risk factor related to cancer of the endometrium. This report considers the estrogen and obesity-related relative risks with regard to various prognostic features of tumors (clinical stage, histologic grade, extent of myometrial invasion, lymph node involvement). In both estrogen users and obese women, the increase in relative risk was greater for earlier than for more advanced tumors. These findings, therefore, provide further support for a specific role of both exogenous and endogenous estrogens in endometrial cancer