Heparanase expression in both normal endometrium and endometrial cancer

The aim of this study was to investigate the relationship between heparanase expression and prognostic factors in endometrial cancer, as well as the relationship between heparanase expression during phases of the normal endometrial cycle. Immunohistochemical analysis of 166 endometrial cancers and 34 normal endometria in various phases of growth was performed. The heparanase expression in the late-proliferative phase of normal endometria was found to be significantly higher than in either the early-proliferative or the secretory phases (P = .012 and P = .044, respectively). Heparanase expression was also significantly higher in endometrial cancer patients with tumors of an advanced FIGO stage (P = .0003) and high FIGO grade (P = .004) and with cancers showing either deep myometrial invasion (P = .023), lymph node metastasis (P = .006), lymphvascular space involvement (P = .048), or positive peritoneal cytology (P = .010). The disease-free and overall survival rates of patients with intense heparanase expression were significantly lower than those of patients with absent or moderate heparanase expression (P = .004 and P = .002, respectively). Heparanase may participate in normal endometrial remodeling and can serve as an indicator of the aggressive potential and poor prognosis of endometrial cancers.

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The Relationship of Myometrial Invasion Between Other Prognostic Parameters in Endometrial Cancer

Gynecology Obstetrics and Reproductive Medicine ◽

10.21613/gorm.2016.648 ◽

2017 ◽

Vol 23 (3) ◽

pp. 158

Author(s):

Mehmet Sait Bakır ◽

Ali Emre Tahaoğlu ◽

Emre Erdoğdu ◽

Cem Dane

Keyword(s):

Endometrial Cancer ◽

Lymph Node ◽

Survival Rates ◽

Disease Free Survival ◽

Myometrial Invasion ◽

Recurrence Rates ◽

Free Survival ◽

Aortic Lymph Node ◽

Deep Myometrial Invasion ◽

The Relationship

Objective: The aim of this study is to investigate the relationship between deep myometrial invasion and other prognostic factors in endometrial cancer. Recurrence rates, disease free survival and overall survival rates were evaluated in endometrial cancer patients with MI>50%.Sudy Design: A total of 132 patients with endometrial cancer who underwent surgical treatment between 2001 and 2011 were identified. Demographic, clinicopathological, surgical/adjuvant treatment and follow-up data were extracted. Results: Pelvic lymph node invasion ratio was 28,9% and para-aortic lymph node invasion ratio was 15,5% in patients with myometrial invasion is greater than 50%. Other prognostic factors especially lympho-vascular space invasion and pelvic/para-aortic lymph node metastasis were significantly higher when myometrial invasion is above 50% and also there was significant difference in recurrence rates, overall survival and disease free survival rates between patients with superficial and deep myometrial invasion (p<0.05).Conclusion: Myometrial invasion is an important prognostic parameter and can be determined intraoperatively to decide whether to perform pelvic and para-aortic lymph node dissection.

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Tumoral volume measured preoperatively by magnetic resonance imaging is related to survival in endometrial cancer

Radiology and Oncology ◽

10.2478/raon-2020-0064 ◽

2021 ◽

Vol 55 (1) ◽

pp. 35-41

Author(s):

Pluvio J. Coronado ◽

Javier de Santiago-López ◽

Javier de Santiago-García ◽

Ramiro Méndez ◽

Maria Fasero ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Endometrial Cancer ◽

Magnetic Resonance ◽

Auxiliary Information ◽

Myometrial Invasion ◽

Figo Stage ◽

Mri Imaging ◽

Resonance Imaging ◽

Deep Myometrial Invasion ◽

Grade 3

AbstractBackgroundThe aim of the study was to determine if the endometrial tumor volume (TV) measured by magnetic resonance imaging (MRI-TV) is associated with survival in endometrial cancer and lymph nodes metastases (LN+).Patients and methodsWe evaluated the MRI imaging and records of 341 women with endometrial cancer and preoperative MRI from 2008 to 2018. The MRI-TV was calculated using the ellipsoid formula measuring three perpendicular tumor diameters. Tumor myometrial invasion was also analyzed.ResultsHigher MRI-TV was associated with age ≥ 65y, non-endometrioid tumors, grade-3, deep-myometrial invasion, LN+ and advanced FIGO stage. There were 37 patients with LN+ (8.8%). Non-endometrioid tumors, deep-myometrial invasion, grade-3 and MRI-TV ≥ 10 cm3 were the factors associated with LN+. Using a receiver operating characteristic [ROC] curve, the MRI-TV cut-off for survival was 10 cm3 (area under curve [AUC] = 0.70; 95% CI: 0.61–0.73). 5 years disease-free (DFS) and overall survival (OS) was significantly lower in MRI-TV ≥ 10 cm3 (69.3% vs. 84.5%, and 75.4% vs. 96.1%, respectively). MRI-TV was considered an independent factor of DFS (HR: 2.20, 95% CI: 1.09–4.45, p = 0.029) and OS (HR: 3.88, 95% CI: 1.34–11.24, p = 0.012) in multivariate analysis.ConclusionsMRI-TV was associated with LN+, and MRI-TV ≥ 10 cm3 was an independent prognostic factor of lower DFS and OS. The MRI-TV can be auxiliary information to plan the surgery strategy and predict the adjuvant treatment in women with endometrial cancer.

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Sonographic and histopathologic characteristics of MMR-deficient endometrial cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17111 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17111-e17111

Author(s):

Daniel Arnold Smith ◽

Raj M Paspulati ◽

Nami R Azar ◽

Kai Laukamp ◽

Elias Kikano ◽

...

Keyword(s):

Endometrial Cancer ◽

Endometrial Thickness ◽

Color Doppler ◽

Transvaginal Ultrasound ◽

Myometrial Invasion ◽

Figo Stage ◽

Initial Presentation ◽

Chi Square ◽

Ultrasound Findings ◽

Endometrial Cancers

e17111 Background: Mismatch repair (MMR) deficiency has emerged as a key biomarker in endometrial cancer with roles in prognosis and guiding therapy. However, the differences of sonographic features between MMR-deficient and MMR-proficient endometrial cancers at initial presentation have not been established. Methods: Transvaginal ultrasound studies of 103 endometrial cancers (60 MMR-deficient, 43 MMR-proficient) at initial presentation were retrospectively analyzed by two experienced radiologists. Histopathologic findings and sonographic features of endometrial morphology recorded according to IETA terminology were compared using Likelihood Ratio Chi-Square and Mann–Whitney U tests. Results: The MMR-deficient group comprised of 90% and the MMR-proficient group of 100% endometrioid subtypes. The following sonographic features were statistically different between MMR-deficient (age 45-95) and MMR-proficient (age 45-83) groups: uniform endometrial echogenicity/pattern, non-uniform endometrial echogenicity/pattern, endometrial midline morphology, presence of a bright edge, and endomyometrial junction morphology. Ultrasound findings of endometrial thickness, synechiae, intracavitary fluid, color Doppler score, and vascular pattern were not significantly different. Statistically significant differences in pathology features included FIGO grade, myometrial invasion, and lymphovascular invasion, while FIGO stage showed no difference. Conclusions: MMR-deficient endometrial cancer is characterized by several statistically different ultrasound and histopathologic features on initial presentation compared to MMR-proficient endometrial cancer.[Table: see text]

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Ultrastaging of ‘negative’ pelvic lymph nodes in patients with low- and intermediate-risk endometrioid endometrial cancer who developed non-vaginal recurrences

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2021-002924 ◽

2021 ◽

pp. ijgc-2021-002924

Author(s):

Sarah E Gill ◽

Simone Garzon ◽

Francesco Multinu ◽

Alexis N Hokenstad ◽

Jvan Casarin ◽

...

Keyword(s):

Endometrial Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Myometrial Invasion ◽

Figo Stage ◽

Peritoneal Cytology ◽

Intermediate Risk ◽

Pelvic Lymph Nodes ◽

Vaginal Recurrence ◽

Lymphovascular Space Invasion

ObjectiveEvidence on micrometastases and isolated tumor cells as factors associated with non-vaginal recurrence in low- and intermediate-risk endometrial cancer is limited. The goal of our study was to investigate risk factors for non-vaginal recurrence in low- and intermediate-risk endometrial cancer.MethodsRecords of all patients with endometrial cancer surgically managed at the Mayo Clinic before sentinel lymph node implementation (1999–2008) were reviewed. We identified all patients with endometrioid low-risk (International Federation of Gynecology and Obstetrics (FIGO) stage I, grade 1 or 2 with myometrial invasion <50% and negative peritoneal cytology) or intermediate-risk (FIGO stage I, grade 1 or 2 with myometrial invasion ≥50% or grade 3 with myometrial invasion <50% and negative peritoneal cytology) endometrial cancer at definitive pathology after pelvic and para-aortic lymph node assessment. All pelvic lymph nodes of patients with non-vaginal recurrence (any recurrence excluding isolated vaginal cuff recurrences) underwent ultrastaging.ResultsAmong 1303 women, we identified 321 patients with low-risk (n=236) or intermediate-risk (n=85) endometrial cancer (median age 65.4 years; 266 (82.9%) stage IA; 55 (17.1%) stage IB). Of the total of 321, 13 patients developed non-vaginal recurrence (Kaplan–Meier rate 4.7% by 60 months; 95% CI 2.1% to 7.2%): 11 hematogenous/peritoneal and two para-aortic and distant lymphatic. Myometrial invasion and lymphovascular space invasion were univariately associated with non-vaginal recurrence. In these patients, the original hematoxylin/eosin slides review confirmed all 646 pelvic and para-aortic removed lymph nodes as negative. The ultrastaging of 463 pelvic lymph nodes did not identify any occult metastases (prevalence 0%; 95% CI 0% to 22.8% considering 13 patients; 95% CI 0% to 0.8% considering 463 pelvic lymph nodes).ConclusionThere were no occult metastases in pelvic lymph nodes of patients with low- or intermediate-risk endometrial cancer with non-vaginal recurrence. Myometrial invasion and lymphovascular space invasion appear to be associated with non-vaginal recurrence.

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Heparanase expression and angiogenesis in endometrial cancer: Analyses of RT-PCR and immunohistochemistry

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5535 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5535-5535

Author(s):

Y. Aoki ◽

M. Inamine ◽

M. Hirakawa ◽

W. Kudaka ◽

Y. Nagai

Keyword(s):

Endometrial Cancer ◽

Tumor Angiogenesis ◽

Microvessel Density ◽

Myometrial Invasion ◽

Tumor Grade ◽

Figo Stage ◽

Clinicopathological Parameters ◽

Strong Positive Correlation ◽

Stage Iiic ◽

Endometrial Cancers

5535 Background: The human heparanase has been shown to function in tumor progression, metastatic spread, and tumor angiogenesis. The aim of the present study was to assess heparanase expression in endometrial cancer in correlation with neovascularization and clinicopathological factors.Methods: Fifty-two endometrial cancers were obtained from previously untreated patients (median age, 56 years; range, 35–80 years). The expression of heparanase mRNA was evaluated using a semi-quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical staining (IHC) with anti-heparanase polyclonal antibody. This antibody was raised by immunizing a rabbit with a peptide containing the amino acid residues from 238 to 250 of the Heparanase. Tumor angiogenesis was assessed using microvessel counting. The Mann-Whitney U test, one factor ANOVA test, and Spearman's test were used to determine the relationship between heparanase expression, microvessel density, and clinicopathological parameters. Results: The expression of heparanase mRNA was detected in 26 of 52 (50%) endometrial cancers, and was significantly correlated with FIGO stage IIIc (p = 0.0075), the presence of lymph-vascular space involvement (LVSI) (p = 0.0041), lymph node metastasis (LNM) (p = 0.0049), and histological tumor grade (p = 0.003). IHC showed that the heparanase was expressed in 23 of 52 (44.2%) endometrial cancers, which was significantly related to LVSI (p = 0.0028), depth of myometrial invasion (p = 0.0026), and histological tumor grade (p = 0.0135). Microvessel density was also associated with FIGO stage IIIc (p = 0.027), LVSI (p = 0.001), LNM (p = 0.038), ovarian metastasis (p = 0.03) and histological tumor grade (p = 0.003). Moreover, we found a strong positive correlation between heparanase expression and microvessel density (r2 = 0.475, p = 0.0001). Conclusions: These results suggest that the expression of heparanase can promote tumor angiogenesis and develop metastasis in endometrial cancer. No significant financial relationships to disclose.

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An immunohistochemical study of estrogen and progesterone receptors in adenocarcinoma of the endometrium and in the adjacent mucosa

International Journal of Gynecological Cancer ◽

10.1046/j.1525-1438.1995.05040275.x ◽

1995 ◽

Vol 5 (4) ◽

pp. 275-281 ◽

Cited By ~ 6

Author(s):

H. Kerner ◽

E. Sabo ◽

M. Friedman ◽

D. Beck ◽

O. Samare ◽

...

Keyword(s):

Estrogen Receptor ◽

Endometrial Cancer ◽

Progesterone Receptor ◽

Estrogen Receptor Status ◽

Endometrial Adenocarcinoma ◽

Progesterone Receptors ◽

Myometrial Invasion ◽

Inverse Correlation ◽

Immunohistochemical Analysis ◽

Receptor Status

The immunoperoxidase stain for estrogen and progesterone receptor content in endometrial adenocarcinoma was correlated with the grade and stage, level of myometrial invasion, age and survival of the patients. Anti-estrogen and anti-progesteone receptor monoclonal antibodies were applied to paraffin-embedded tissue from hysterectomy specimens of 100 patients with adenocarcinoma of the endometrium. In 34 of the cases the receptors were studied in the endometrium adjacent to the tumor and compared to the nuclear receptor content in the carcinoma. There was a high inverse correlation between the estrogen receptor status and the grade of tumor (R= − 0.45,P= 0.006). The estrogen receptor measured in the endometrium near the tumor showed a negative correlation with the grade of the tumor (R= −0.42,P= 0.013). The estrogen, but not the progesterone, receptor content, was positively related to the age of the patient (P< 0.05). No significant correlation of the receptor status with the depth of myometrial invasion was found, despite the obvious interdependence between the grade and myometrial invasion. The progesterone receptor staining index appeared to be a distinct independent prognostic factor in endometrial cancer. The immunohistochemical analysis of the steroid hormone status in endometrial cancer therefore offers an alternative to the quantitative ligand-binding assay.

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Intraoperative Gross Examination and Intraoperative Frozen Section in Patients With Endometrial Cancer for Detecting Deep Myometrial Invasion

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000618 ◽

2016 ◽

Vol 26 (2) ◽

pp. 407-415 ◽

Cited By ~ 14

Author(s):

Juan Luis Alcazar ◽

Jaime Dominguez-Piriz ◽

Leire Juez ◽

Maria Caparros ◽

Matias Jurado

Keyword(s):

Endometrial Cancer ◽

Frozen Section ◽

Myometrial Invasion ◽

Intraoperative Frozen Section ◽

Deep Myometrial Invasion ◽

Gross Examination

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Radiomic machine learning for pretreatment assessment of prognostic risk factors for endometrial cancer and its effects on radiologists' decisions of deep myometrial invasion

Magnetic Resonance Imaging ◽

10.1016/j.mri.2021.10.024 ◽

2021 ◽

Author(s):

Satoshi Otani ◽

Yuki Himoto ◽

Mizuho Nishio ◽

Koji Fujimoto ◽

Yusaku Moribata ◽

...

Keyword(s):

Machine Learning ◽

Risk Factors ◽

Endometrial Cancer ◽

Myometrial Invasion ◽

Pretreatment Assessment ◽

Deep Myometrial Invasion ◽

Prognostic Risk Factors

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Lymph Node Metastasis in Patients With Endometrioid Endometrial Cancer: Overtreatment Is the Main Issue

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000937 ◽

2017 ◽

Vol 27 (4) ◽

pp. 748-753 ◽

Cited By ~ 8

Author(s):

Alper Karalok ◽

Taner Turan ◽

Derman Basaran ◽

Osman Turkmen ◽

Gunsu Comert Kimyon ◽

...

Keyword(s):

Endometrial Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Histological Grade ◽

Myometrial Invasion ◽

Lymph Node Involvement ◽

Node Metastasis ◽

Deep Myometrial Invasion ◽

Endometrioid Endometrial Cancer ◽

Grade 3

ObjectiveThe aim of this study was to evaluate the effectiveness of histological grade, depth of myometrial invasion, and tumor size to identify lymph node metastasis (LNM) in patients with endometrioid endometrial cancer (EC).MethodsA retrospective computerized database search was performed to identify patients who underwent comprehensive surgical staging for EC between January 1993 and December 2015. The inclusion criterion was endometrioid type EC limited to the uterine corpus. The associations between LNM and surgicopathological factors were evaluated by univariate and multivariate analyses.ResultsIn total, 368 patients were included. Fifty-five patients (14.9%) had LNM. Median tumor sizes were 4.5 cm (range, 0.7–13 cm) and 3.5 cm (range, 0.4–33.5 cm) in patients with and without LNM, respectively (P = 0.005). No LMN was detected in patients without myometrial invasion, whereas nodal spread was observed in 7.7% of patients with superficial myometrial invasion and in 22.6% of patients with deep myometrial invasion (P < 0.0001). Lymph node metastasis tended to be more frequent in patients with grade 3 disease compared with those with grade 1 or 2 disease (P = 0.131).ConclusionsThe risk of lymph node involvement was 30%, even in patients with the highest-risk uterine factors, that is, those who had tumors of greater than 2 cm, deep myometrial invasion, and grade 3 disease, indicating that 70% of these patients underwent unnecessary lymphatic dissection. A precise balance must be achieved between the desire to prevent unnecessary lymphadenectomy and the ability to diagnose LNM.

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