scholarly journals Redefining Stage I Endometrial Cancer: Incorporating Histology, a Binary Grading System, Myometrial Invasion, and Lymph Node Assessment

2013 ◽  
Vol 23 (9) ◽  
pp. 1620-1628 ◽  
Author(s):  
Joyce N. Barlin ◽  
Robert A. Soslow ◽  
Megan Lutz ◽  
Qin C. Zhou ◽  
Caryn M. St. Clair ◽  
...  

ObjectiveWe propose a new staging system for stage I endometrial cancer and compare its performance to the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) systems.MethodsWe analyzed patients with 1988 FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas (serous, clear cell, and carcinosarcoma). The proposed system is as follows:IA. Low-grade carcinoma with less than half myometrial invasionIA1: Negative nodesIA2: No nodes removedIB. High-grade carcinoma with no myometrial invasionIB1: Negative nodesIB2: No nodes removedIC. Low-grade carcinoma with half or greater myometrial invasionIC1: Negative nodesIC2: No nodes removedID. High-grade carcinoma with any myometrial invasionID1: Negative nodesID2: No nodes removedResultsData from 1843 patients were analyzed. When patients were restaged with our proposed system, the 5-year overall survival significantly differed (P < 0.001): IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1, 81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate for the proposed system was 0.627 (95% confidence interval, 0.590–0.664) and was superior to the concordance probability estimate of 0.530 (95% confidence interval, 0.516–0.544) for the 2009 FIGO system.ConclusionsBy incorporating histological subtype, grade, myometrial invasion, and whether lymph nodes were removed, our proposed system for stage I endometrial cancer has a superior predictive ability over the 2009 FIGO staging system and provides a novel binary grading system (low-grade including endometrioid grade 1–2 lesions; high-grade carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid carcinomas).

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 274
Author(s):  
Miłosz Pietrus ◽  
Michał Seweryn ◽  
Przemysław Kapusta ◽  
Paweł Wołkow ◽  
Kazimierz Pityński ◽  
...  

Endometrial cancer (EC) is treated according to the stage and prognostic risk factors. Most EC patients are in the early stages and they are treated surgically. However some of them, including those with high grade (grade 3) are in the intermediate and high intermediate prognostic risk groups and may require adjuvant therapy. The goal of the study was to find differences between grades based on an miRNA gene expression profile. Tumor samples from 24 patients with grade 1 (n = 10), 2 (n = 7), and 3 (n = 7) EC were subjected to miRNA profiling using next generation sequencing. The results obtained were validated using the miRNA profile of 407 EC tumors from the external Cancer Genome Atlas (TCGA) cohort. We obtained sets of differentially expressed (DE) miRNAs with the largest amount between G2 to G1 (50 transcripts) and G3 to G1 (40 transcripts) patients. Validation of our results with external data (TCGA) gave us a reasonable gene overlap of which we selected two miRNAs (miR-375 and miR190b) that distinguish the high grade best from the low grade EC. Unsupervised clustering showed a high degree of heterogeneity within grade 2 samples. MiR-375 as well as 190b might be useful to create grading verification test for high grade EC. One of the possible mechanisms that is responsible for the high grade is modulation by virus of host morphology or physiology.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5009-5009
Author(s):  
Emily Meichun Ko ◽  
Jason Franasiak ◽  
Leslie Horn Clark ◽  
Paola A. Gehrig ◽  
Victoria Lin Bae-Jump

5009 Background: Obesity and diabetes (DM) have been linked to increased recurrence rates and worse survival in endometrial cancer. Metformin is widely used as the first line treatment for type II DM. Recent epidemiological evidence suggests that metformin may lower cancer risk and reduce cancer-related deaths among DM patients. However, no studies have assessed the effect of metformin use on endometrial cancer outcomes. Methods: A retrospective cohort analysis was conducted of all grade 3 endometrial cancer patients with DM at a single institution from 2005-2010. Clinical-pathologic data was abstracted, including metformin, insulin, sulfonamide and thiazolidinedione use at the time of cancer diagnosis. Statistical analysis were performed using summary statistics and multivariate cox analysis, with two tailed p-values <0.05 considered significant. Results: 55/329 patients with grade 3 cancer had DM. Mean age was 68.3 (sd 8.4), and BMI 35.7 (sd 9.4). Stage distribution consisted of 58.2% stage I, 7.3% stage II, 27.3% stage III, and 7.3% stage IV. Histology included 41.8% endometrioid, and 58.2% serous or clear cell. 56.4% of diabetics used metformin and 43.6% did not. Mean follow-up was 21.6 months (sd 15.0). After adjusting for BMI, myometrial invasion, stage, histology, adjuvant treatment, and non-metformin DM medications, metformin use was significantly associated with decreased cancer recurrence (HR 0.06, 95CI 0.01, 0.40; p<0.004). Conclusions: Metformin use was associated with a decreased risk of recurrence in high-grade endometrial cancer, suggesting that it may have a role as adjuvant and maintenance therapy for this obesity-driven disease. [Table: see text]


2011 ◽  
Vol 71 (05) ◽  
Author(s):  
AH Brunner ◽  
P Riss ◽  
G Heinze ◽  
E Meltzow ◽  
H Brustmann

2020 ◽  
Author(s):  
Adnan Budak ◽  
Emrah Beyan ◽  
Abdurrahman Hamdi Inan ◽  
Ahkam Göksel Kanmaz ◽  
Onur Suleyman Aldemir ◽  
...  

Abstract Aim We investigate the role of preoperative PET parameters to determine risk classes and prognosis of endometrial cancer (EC). Methods We enrolled 81 patients with EC who underwent preoperative F-18 FDG PET/CT. PET parameters (SUVmax, SUVmean, MTV, TLG), grade, histology and size of the primary tumor, stage of the disease, the degree of myometrial invasion (MI), and the presence of lymphovascular invasion (LVI), cervical invasion (CI), distant metastasis (DM) and lymph node metastasis (LNM) were recorded. The relationship between PET parameters, clinicopathological risk factors and overall survival (OS) was evaluated. Results The present study included 81 patients with EC (mean age 60). Of the total sample, 21 patients were considered low risk (endometrioid histology, stage 1A, grade 1 or 2, tumor diameter < 4 cm, and LVI negative) and 60 were deemed high risk. All of the PET parameters were higher in the presence of a high-risk state, greater tumor size, deep MI, LVI and stage 1B-4B. MTV and TLG values were higher in the patients with non-endometrioid histology, CI, grade 3 and LNM. The optimum cut-off levels for differentiating between the high and low risk patients were: 11.1 for SUVmax (AUC = 0.757), 6 for SUVmean (AUC = 0.750), 6.6 for MTV(AUC = 0.838) and 56.2 for TLG(AUC = 0.835). MTV and TLG values were found as independent prognostic factors for OS, whereas SUVmax and SUVmean values were not predictive. Conclusions The PET parameters are useful in noninvasively differentiating between risk groups of EC. Furthermore, volumetric PET parameters can be predictive for OS of EC.


2017 ◽  
Vol 27 (4) ◽  
pp. 748-753 ◽  
Author(s):  
Alper Karalok ◽  
Taner Turan ◽  
Derman Basaran ◽  
Osman Turkmen ◽  
Gunsu Comert Kimyon ◽  
...  

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.


2010 ◽  
Vol 4 (1) ◽  
pp. 34-43
Author(s):  
Zainab M. T. Jafer ◽  
Esmail K. Shubber

The study has been done on 36 samples of biopsies which drawn from patients suffered from ulcerative colitis, the samples were taken from female & male of different ages. The goal was to observe the gene expression of the suppresser tumor gene P53, & the suppresser apoptosis gene Bcl-2, by using in situ hybridization technique. The results showed that there were relationships between both genes (P53 & Bcl-2) in patients suffered from ulcerative colitis compared with healthy individuals. The suppresser gene P53 gave 63% in the high grade(3) , 29 % in the intermediate stage (2) & 8% in the low grade (1) .While for the suppresser apoptosis gene Bcl-2 , the results showed increasing in the activity of this gene , which gave 66% in the high grade(3) , 27% in the intermediate stage (2) , & 7% in the low grade (1) . These results indicate accumulated mutations in the gene P53 & increase in the activity of gene Bcl-2 in inflamed colonic tissue of chronic ulcerative colitis. This gave an indication of early detection for diagnostic, therapeutic and monitoring purposes.


2019 ◽  
Vol 14 ◽  
pp. 117727191986489
Author(s):  
Cao Jin ◽  
Sean Hacking ◽  
Miglena K Komforti ◽  
Mansoor Nasim

Background: Death domain-associated protein 6 (DAXX) is involved in regulating apoptosis via subcellular localization. The presence of DAXX point mutations correlates well with loss of nuclear expression on immunohistochemistry (IHC). In this study, we sought to determine (1) whether DAXX expression pattern is the same across different uterine carcinoma subtypes, and (2) which uterine carcinomas show loss of nuclear DAXX IHC. Design: We studied 65 uterine carcinomas of the following histologic types: 30 endometrioid (12 FIGO [The International Federation of Gynecology and Obstetrics] grade 1, 12 FIGO grade 2, and 6 FIGO grade 3), 8 serous, 14 clear cell, and 13 undifferentiated/dedifferentiated type (UEC/DDEC). Nuclear DAXX IHC was assessed in each tumor and was graded semi-quantitatively as follows: 0% to 50%, 50% to 75%, and greater than 75% of lesional cells react. Results: A total of 61% (25/41) of high-grade carcinomas (FIGO grade 3, serous, clear cell, and UEC/DDEC]) showed retained DAXX nuclear staining in >75% of lesional cells, compared with only 4.2% (1/24) of the low-grade carcinomas (FIGO grades 1 and 2) ( P = .0001), where DAXX expression was cytoplasmic. In addition, in the 11 DDEC cases, all the differentiated components showed loss of nuclear DAXX compared with the undifferentiated components which retained nuclear DAXX expression. Conclusions: We demonstrate that loss of nuclear DAXX is present in low-grade endometrial carcinomas and the differentiated components in UEC/DDEC, but not in high-grade ones, suggesting DAXX’s role in tumor progression and its potential as a therapeutic target in high-grade endometrial carcinomas.


Author(s):  
John M. Anderson ◽  
Tam Nguyen ◽  
Joel Childers ◽  
Alton V. Hallum ◽  
Earl Surwitt ◽  
...  

2017 ◽  
Vol 59 (3) ◽  
pp. 363-370 ◽  
Author(s):  
Bin Yan ◽  
Tingting Zhao ◽  
Xiufen Liang ◽  
Chen Niu ◽  
Caixia Ding

Background Diffusion-weighted imaging (DWI) provides useful information for the identification of benign and malignant uterine lesions. However, the use of the apparent diffusion coefficient (ADC) for histopathological grading of endometrial cancer is controversial. Purpose To explore the use of ADC values in differentiating the preoperative tumor grading of endometrioid adenocarcinomas and investigate the relationship between the ADC values of endometrial cancer and the histological tumor subtype. Material and Methods We retrospectively evaluated 98 patients with endometrial cancers, including both endometrioid adenocarcinomas (n = 80) and non-endometrioid adenocarcinomas (n = 18). All patients underwent DWI procedures and ADC values were calculated. The Kruskal–Wallis test and the independent samples Mann–Whitney U test were used to compare differences in the ADC values between different tumor grades and different histological subtypes. Results The mean ADC values (ADCmean) for high-grade endometrioid adenocarcinomas were significantly lower than the values for low-grade tumors (0.800 versus 0.962 × 10–3 mm2/s) ( P = 0.002). However, no significant differences in ADCmean and minimum ADC values (ADCmin) were found between tumor grades (G1, G2, and G3) of endometrial cancer. Compared with endometrioid adenocarcinomas, the adenocarcinoma with squamous differentiation showed lower ADC values (mean/minimum = 0.863/0.636 versus 0.962/0.689 × 10–3 mm2/s), but the differences were not significant ( Pmean = 0.074, Pmin = 0.441). Moreover, ADCmean for carcinosarcomas was significantly higher than the value for G3 non-carcinosarcoma endometrial cancers (1.047 versus 0.823 × 10–3 mm2/s) ( P = 0.001). Conclusion The ADCmean was useful for identifying high-grade and low-grade endometrioid adenocarcinomas. Additionally, squamous differentiation may decrease ADCmean and ADCmin of endometrioid adenocarcinoma, and carcinosarcomas showed relatively high ADCmean.


2004 ◽  
Vol 14 (4) ◽  
pp. 665-672 ◽  
Author(s):  
F. Alexander-Sefre ◽  
N. Singh ◽  
A. Ayhan ◽  
J. M. Thomas ◽  
I. J. Jacobs

BackgroundThere is a strong correlation between disease mortality and the depth of myometrial invasion in stage I endometrial cancer (EC). Current assessment of the depth of invasion relies on light microscopy. Tumor cells can evade detection by light microscopy if they are vastly outnumbered by myometrial cells. Immunohistochemical (IHC) techniques against pancytokeratins (PCKs) have a great potential in the detection of such isolated cells.ObjectivesTo investigate the application of IHC techniques in the identification of isolated infiltrating tumor cells within myometrium and assess its significance in clinically stage I EC.MethodsA single representative tissue block containing the deepest myometrial invasion by the tumor was selected for 90 patients with stage I EC. Sections from each block were immunostained in accordance with established streptavidin–biotin peroxidase method using a mouse monoclonal antikeratin clone AE1/AE3. Myometrium was re-examined to identify deeper myometrial invasion that had escaped detection on hematoxylin and eosin (H&E) section. The clinical records were reviewed, and following data were collected: age, race, parity, presentation, associated medical disorders (obesity, diabetes, and hypertension), use of tamoxifen or hormone replacement therapy, menopausal state, recurrence, and survival.ResultsOf 90 cases, deeper myometrial invasion was detected on IHC sections in seven cases (7.7%). In five of these seven cases, isolated tumor cells surrounded by inflammatory cells were noted 0.2–1.2 mm deeper within the myometrium than that detected by H&E staining. In the remaining two cases, the deeper extension seen was the result of examining serial levels through the tumor block; in these cases, deeper infiltration should have been apparent on H&E sections. Follow-up data was available in 72 of the 90 cases. A trend was noted between the presence of isolated tumor cells deeper within myometrium on IHC and tumor recurrence (P = 0.056). The 2-year recurrence-free survival was 40% for the group with IHC evidence of deeper invasion compared with 89% for the group without (P = 0.005). Similarly, analysis of cause-specific and overall survival revealed significant differences between the two groups (P = 0.038 and P = 0.026, respectively).ConclusionsIn this study, we have shown that it is possible to identify deeper level of myometrial invasion by tumor cells using an IHC technique. IHC-detected deeper invasion is an uncommon event and may be a feature of more aggressive tumors with greater potential for recurrence and lower survival.


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