A Selective Biomarker Panel Increases the Reproducibility and the Accuracy in Endometrial Biopsy Diagnosis.

Serine proteases HTRA1 and HTRA3 are down-regulated with increasing grades of human endometrial cancer

Mini-resectoscopy Endometrial Biopsy Accuracy Respect Dilatation and Curettage in Endometrial Cancer: A Retrospective Analysis

The role of volumetric ADC histogram analysis in preoperatively evaluating the tumour subtype and grade of endometrial cancer

We aimed to evaluate the correlation between the histological grade of endometrial cancer diagnosed on endometrial biopsy or curettage, with the definitive grade and stage of lesion as determined by surgery and histopathological examination and to make recommendations about the suitability of conservative surgery based on pre-operative determination of the grade of endometrial adenocarcinoma. A retrospective review of all patients with endometrial adenocarcinoma presenting to the Queensland Centre for Gynaecological Cancer from 1 January 1996 to 31 December 1998 was undertaken. Clinical and pathological data was abstracted from medical records and case notes of 460 patients. All histological specimens were prospectively reviewed by a panel consisting of gynaecologic pathologists, gynaecologic oncologists and other doctors involved in the treatment of patients with gynaecological malignancies. The percentage of patients whose management would have been optimised by full surgical staging at the time of initial surgery was calculated. Only 60%, 71%, and 84 % of the patients with a presenting diagnosis of grade 1, 2 and 3 endometrial adenocarcinomas respectively had this confirmed on final histopathology. Furthermore, using established criteria, 30%, 46% and 100% of patients presenting with grade 1, 2 and 3 endometrial adenocarcinoma required full surgical staging at the time of their primary surgery There is poor correlation between the pre-operative grade of endometrial cancer and the grade as determined on analysis of the resected uterus. The correlation is poorest with grade 1 endometrial adenocarcinoma, where strongest consideration is given to conservative surgery and the avoidance of subspecialty referral. There is a strong argument that all patients with a diagnosis of endometrial cancer made on endometrial biopsy or curettage, regardless of grade of malignancy, should be offered surgery where the option to perform concurrent comprehensive surgical staging is available.

Identification of patients with stage I uterine endometrioid adenocarcinoma at high risk of recurrence by DNA ploidy, myometrial invasion, and vascular invasion

Development of endometrial cancer after radiation treatment for cervical carcinoma

Objective The aim of this study was to correlate the level of CA125 in different stages, histopathological types, and grades of endometrial cancer. Patients and methods Prospective study was conducted on 120 endometrial cancer patients who underwent full surgical staging, preoperative measurement of CA125, histopathological examination, and grading of uterus and pelvic lymph nodes. Results Histopathology of the cases revealed the following: 102 cases were endometrioid adenocarcinoma, 17 cases were serous papillary adenocarcinoma, and one case was clear cell carcinoma. All 25 (100%) cases with advanced-stage disease had a CA-125 level of at least 35 U\ml, compared with 52 of 95 (54.7%) cases with early-stage disease (P<0.001). In relation to histopathological type and CA-125 serum level, all the 18 (100%) nonendometrioid-type cases had a CA-125 level of greater than or equal to 35 U\ml in comparison with 59 of 102 (57.8%) endometriod cases (P=0.001). In contrast to histopathological grading, there was no positive correlation (P=0.36). Conclusion Preoperative CA125 serum levels of at least 35 U\ml in uterine adenocarcinoma can predict advanced disease stages (III or IV), regional lymph nodes metastasis, and high risk patients who need regional lymphadenectomy and complete surgical staging.

DNA aneuploidy is associated with increased mortality for stage I endometrial cancer

The objective of this study is to compare the accuracy of tumor grade in endometrial cancer between fractional dilatation and curettage (D&C) and postoperative hysterectomy specimen findings. From January 2000 to November 2002, 52 women with abnormal vaginal bleeding and diagnosed or suspected endometrial cancer were treated in the Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Second Medical University. The comparison of tumor grades was performed on both D&C and hysterectomy specimens, the relationship between the concordance rate of grade, and the depth of tumor invasion into the myometrium. The expression of estrogen receptor (ER), progesterone receptor (PR), p53, Bcl2, and proliferation cell nuclear antigen (PCNA) in tumor samples were analyzed. The concordance rates were 20% in grade 1, 61.5% in grade 2, and 77.8% in grade 3. The concordance rates for grade 2 and grade 3 were higher than grade 1 significantly (grade 2 approximately grade 1, P=0.010; grade 3 approximately grade 1, P=0.005). Fourteen out of 52 (26.9%) patients diagnosed with atypical endometrial hyperplasia by D&C had their diagnosis changed to endometrial cancer after being ascertained by hysterectomy specimen. The accuracy of tumor grade diagnosis by D&C was 50%, and 48% of patients were downgraded after comparison of postoperative specimens. The concordance rate of tumor invasion into the outer half of myometrium was higher than in tumors localized in the endometrium (P= 0.030). No association between high concordance rate and the expression of ER, PR, p53, Bcl-2 and PCNA was found. We concluded that D&C had a high accuracy in the diagnosis of endometrial cancer in grade 3 tumors (77.8%) and tumor invasion into the outer half of the myometrium (75%). Overall, 48% of endometrial cancer patients' tumor grades seemed to be decreased by D&C evaluation; thus, the diagnosis of endometrial disorders by D&C should not be overlooked.

Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1–2 endometrial cancer

The objective of this study was to examine the usefulness of transvaginal color Doppler ultrasound (TV-CDU) in differentiating between endometrial hyperplasia (EH) and endometrial carcinoma (EC) and in predicting tumor spread in patients with EC. Seventy-one postmenopausal patients were enrolled with either EH or EC that had been diagnosed by endometrial biopsy. The presence or absence of intratumoral blood flow was assessed by TV-CDU. The intratumoral blood flow characteristics were analyzed using the resistance index (RI), pulsatility index (PI), and peak systolic velocity (PSV). The endometrial thickness also was measured in all patients by gray-scale sonography. The correlation of these sonographic findings with histologic type, tumor grade, surgical stage, myometrial invasion, or the presence or absence of pelvic lymph node metastasis was then evaluated in patients with EC. Although there were no patients with EC with endometrial thickness measuring < 5 mm, no significant difference was found in the mean value of endometrial thickness between patients with EH (n = 18 patients; 16.2 mm +/- 15.9 mm) and patients with EC (n = 53 patients; 18.7 mm +/- 17.1 mm). Intratumoral blood flow was detected in significant numbers of patients who had EC (71.7%; 38 of 53 patients) compared with patients who had EH (5.6%; 1 of 18 patients; P < 0.0001). Thus, no patients with EH showed any blood flow in the endometrial lesions, except for one patient who had EH complicated by pyometra. In patients with EC, the positive rate of intratumoral blood flow was correlated significantly with myometrial invasion, tumor grade, and pelvic lymph node metastasis (P < 0.05; Cochran-Armitage trend test). No associations were found between RI, PI, or PSV and the clinicopathologic parameters examined, including surgical stage. TV-CDU may be more useful in differentiating between EH and EC than measuring endometrial thickness by transvaginal gray-scale sonography. For patients with EC, the detection of intratumoral blood flow may be helpful in distinguishing between low-grade and high-grade tumors and predicting myometrial invasion. However, intratumoral blood flow analysis using RI, PI, or PSV may not be useful for predicting tumor spread before surgery.

Endometrial carcinoma (EC) is the most common gynecologic cancer in industrialized countries. Traditional prognostic markers include FIGO stage, histologic subtype, and histologic grade. DNA ploidy was introduced as a prognostic marker 30 years ago, and the majority of published literature demonstrates significant associations between tumor aneuploidy and poorer prognosis in EC. However, ploidy analysis is not routinely implemented in the clinic. We reviewed the literature on clinical value of ploidy measured by DNA content as a prognostic marker, and its potential role as a predictive marker in EC. PubMed was searched for papers evaluating the prognostic or predictive role of ploidy in EC. Search criteria were "DNA ploidy prognosis/predictive value endometrial cancer/carcinoma". Only articles written in English, published year 2000 or later were included. The majority of the studies demonstrated highly significant correlation between DNA index (DI) and survival, in univariate analysis including stages I-IV, and in subgroup analysis of stage I and stage I-II EC. Several studies also showed significant association between DI and survival in multivariate analysis. Few studies have evaluated DI as a prognostic marker in a prospective setting. No studies evaluating DI as a predictive marker in EC were identified. In other cancer types, ploidy has been linked to prediction of response to hormonal therapy and chemotherapy. Ploidy assessment in EC by DI is a strong prognostic marker. Still, its clinical applicability needs validation in a routine diagnostic, prospective setting with sufficient number of patients, characterized by state of the art histopathological evaluation and surgical staging.

To assess the diagnostic value of dynamic contrast-enhanced (DCE) perfusion-magnetic resonance imaging (MRI) in detection, characterization and grading of endometrial cancer, using histopathological analysis as the standard of reference. Eighty patients with histologically proven endometrial carcinoma who underwent MRI (1.5 T magnet) of the pelvis for staging purposes were enrolled in the study. Each MR examination consisted of multiplanar T2 and T1-weighted turbo spin echo (TSE) sequences and T1-weighted gradient echo sequences before, during and after the administration of contrast medium. For each patient colour perfusion maps were derived from the dynamic sequences using a dedicated workstation. On the maps a region of interest was manually drawn both on normal myometrium and on the endometrial lesion. Then the following perfusion parameters were automatically calculated: relative enhancement (RE, %), maximum enhancement (ME, %), maximum relative enhancement (MRE, %) and time to peak (TTP, s). All patients underwent total hysterectomy. Histopathological analysis documented: G1 tumour in 21 patients, G2 tumour in 44 patients, G3 tumour in 14 patients and one squamous cell carcinoma. The following mean value perfusion parameters, with corresponding mean standard deviation, were obtained for endometrial cancer: RE (%) = 59.3 ± 36.3; ME (%) = 862.7 ± 475.9; MRE (%) = 75.3 ± 37.6 and TTP (s) = 164.7 ± 78. RE, ME and MRE were lower in tumour lesions than in normal myometrium (p < 0.001) and significantly higher values (p < 0.001) of perfusion parameters were obtained for G1 (well-differentiated) tumours as compared to those in G2 and G3 (moderately and poorly differentiated) lesions. DCE perfusion-MRI can provide quantitative information on tissue vascularity, which may be of help in detecting endometrial cancer and in the assessment of tumour grading.

We aim to compare endometrial cancer survival in women with or without histological proven endometriosis or adenomyosis. We identified all women with endometrial cancer between 1990 and 2015 from the Netherlands Cancer Registry (NCR). Data were linked to the Dutch pathology database (PALGA) to select all women with histological proven endometriosis/adenomyosis. Overall survival was compared between women with endometrial cancer with or without endometriosis/adenomyosis. We used multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs). We included 1701 women with endometrial cancer and endometriosis/adenomyosis, of whom 1236 (72.7%) women had adenomyosis, 320 (18.8%) had endometriosis and 145 (8.5%) had both. We compared these women to 39 139 women with endometrial cancer without endometriosis/adenomyosis. Women in the combined endometriosis/adenomyosis cohort were younger at endometrial cancer diagnosis, had earlier disease stage, more often had endometrioid endometrial cancer and low grade tumors. The 5‐year survival rate in the combined endometriosis/adenomyosis cohort was 84.8% (95% CI 84.6‐88.1) and 71.6% (95% CI 71.1‐72.0) in the nonendometriosis/adenomyosis cohort. Univariable analysis resulted in a crude HR of 0.63 (95% CI 0.59‐0.69). Significant confounding factors were age, stage, cancer subtype, histological grading, surgery and chemotherapy rate. Correction for these confounders resulted in a HR of 0.98 (95% CI 0.90‐1.06). Including endometriosis/adenomyosis status as a categorical factor resulted in similar HRs. In conclusion, women with endometrial cancer and histologically proven endometriosis/adenomyosis have a better overall survival when compared to women with endometrial cancer without endometriosis/adenomyosis. This better survival was correlated to stage, grade, age and histological subtype, but not to the presence of endometriosis/adenomyosis.

Postmenopausal bleeding is a clinically important complaint in general gynecologic practice. The incidence of spontaneous postmenopausal bleeding in the general population is approximately 10 % immediately after menopause, and 5 % in all menopausal women. The study was aimed to reveal the histopathologic diagnosis of postmenopausal uterine bleeding, and to investigate the correlation between various clinical factors and endometrial carcinoma. We also evaluated the role of endometrial volume calculation in the clinical use for the endometrial histopathologic findings. In this prospective observational study, we recruited 163 postmenopausal women with abnormal uterine bleeding from January 2008 through December 2010. Women who had hematologic disease, or had nonuterine pelvic diseases were excluded. Clinical characteristics such as age, body mass index (BMI), associated diseases, and previous postmenopausal hormone therapy were checked. They were evaluated by transvaginal ultrasonography and underwent endometrial biopsy for the endometrial histopathologic examination. Among the endometrial histopathologic findings, atrophic endometrium was the most common finding (32.7 %), followed by hyperplastic endometrium (10.4 %), endometrial carcinoma (10.4 %), and endometrial polyp (9.2 %). The prevalence of endometrial hyperplasia and cancer was not significantly different at the 5 mm cut-off thickness of the endometrium, but significantly higher in women with ≥ 3 mL of endometrial volume. However, the incidence of endometrial cancer and hyperplasia in women with endometrial bleeding was not significantly different with or without previous or current hormone therapy. Endometrial biopsy should be performed to exclude endometrial hyperplasia and carcinoma in postmenopausal women with endometrial bleeding to perform proper and prompt treatment, especially in old aged women (> 60 years) and in patients with endometrial volume ≥ 3 mL.