Substantial lymph-vascular space invasion (LVSI) as predictor of distant relapse and poor prognosis in low-risk early-stage endometrial cancer

ObjectiveThe aim of this study is to analyze the prognostic role of lymph-vascular space invasion (LVSI), evaluated in a semi-quantitative fashion on prognosis of early stage, low risk endometrial cancer (EC).MethodsWe enrolled patients who underwent surgery for endometrial cancer between 2003 and 2018 in two referral cancer center. All patients had endometrioid EC, G1–G2, with myometrial invasion <50%, and no lymph-node involvement. LVSI was analyzed in a semi-quantitative way, according to a 3-tiered scoring system in absent, focal and substantial.ResultsAmong 524 patients, any positive LVSI was found in 57 patients (10.9%) with focal LVSI (n=35, 6.7%) and substantial LVSI (n=22, 4.2%). Substantial LVSI was associated to higher rate of G2 (p<0.001), myometrial infiltration (p=0.002) and greater tumor dimensions (p=0.014). Patients with substantial LVSI were more likely to receive adjuvant treatment (6.6% vs. 52.6%, p<0.001). The 5-year OS was 99.5% in patients with absent LVSI and 70.6% in those with substantial LVSI (p<0.001). The 5-year disease free survival (DFS) was 93.6% in patients with absent LVSI and 56.5% in those with substantial LVSI (p<0.001). The rate of distant failures increased from 1.8% for absent LVSI to 22.7% for substantial LVSI (p=0.002). In univariate analysis substantial LVSI was the strongest predictor of poor overall survival (hazard ratio [HR]=11.9, p=0.001). Multivariate analysis showed that substantial LVSI was an independent predictive factor of both recurrence (HR=5.88, p=0.001) and distant failure (HR=10.6, p=0.006).ConclusionsSubstantial LVSI represents the strongest independent risk factor for decreased survival and distant relapse, indicating a role for potential hematogenous dissemination.     

Predicting Factors for Pelvic Lymph Node Metastasis in Patients with Apparently Early-Stage Endometrial Cancer

Background: Performing lymphadenectomy in all patients with early-stage endometrial cancer (EC) is debatable because the procedure may expose patients to unnecessary risks of postoperative complications. Aim of this study was to evaluate the prevalence and risk factors of pelvic lymph node metastasis (PLNM) in patients with apparently early-stage EC. Materials and methods: Two hundred and two patients with apparently early-stage EC who underwent surgical staging at Thammasat University Hospital between the years 2013 and 2020 were included in this retrospective study. Clinicopathological data and preoperative laboratory results were obtained from computer-based medical records. All data were statistically analyzed to determine the prevalence of PLNM and risk factors for developing PLNM. Results: PLNM was detected in 22 (10.9%) patients. Univariate analysis demonstrated that having grade 3 tumor, myometrial invasion of 50% or greater, vaginal involvement, cervical involvement, adnexal involvement, lower uterine segment involvement, lymphovascular space invasion (LVSI), and positive peritoneal cytology were associated with higher risk for developing PLNM. In addition, lower preoperative hemoglobin level and higher preoperative white blood cell count were significantly associated with PLNM. Multivariate analysis demonstrated that myometrial invasion of 50% or greater and LVSI were independent risk factors for developing PLNM (odds ratio (OR) 9.31, 95% confidence interval (CI) 2.58-33.55, p = 0.001, and OR 3.73, 95%CI 1.39-10.02, p = 0.009, respectively). Conclusions: Myometrial invasion of 50% or greater and LVSI were independent risk factors for developing PLNM in patients with apparently early-stage EC and thus lymphadenectomy in these patients should be provided.     

Lymphovascular space invasion as a prognostic determinant in uterine cancer.

The objective of this study was to evaluate the clinical significance of lymphovascular space invasion (LVSI) in patients with uterine cancer in terms of lymph node metastasis, recurrence and survival rate. A total of 190 patients with newly diagnosed uterine cancer who underwent total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), omentectomy, peritoneal washing or ascitic fluid collection, and pelvic/paraaortic lymph node sampling at Chiang Mai University Hospital between January 1999 and December 2004 were evaluated. All medical records and histopathologic slides were retrospectively reviewed to determine the relationship between LVSI and clinicopathological characteristics. LVSI was present in 79 patients (42%) and significantly correlated with lymph node metastasis (p0.001), BMI 25 kg/m2 (p0.001), advanced FIGO stage (p 0.001), poor histologic grade (p0.001), and deep uterine invasion (p0.001). Patients with LVSI, when stratified by FIGO stage, also had a significant lower 5-year survival rate. For those who had disease recurrence, LVSI and histologic grade were found to be independent prognostic factors in a multivariate analysis. LVSI was one of the prognostic determinants for disease recurrence and associated with poor survival in patients with uterine cancer.     

Lymphovascular space invasion in endometrial carcinoma: Tumor size and location matter

ObjectiveTo analyze histological factors possibly associated with lymphovascular space invasion (LVSI) and to determine which of those can act as independent surrogate markers.MethodsRetrospective cohort study performed between January 2001 and December 2014. LVSI was defined as the presence of tumor cells inside a space completely surrounded by endothelial cells. Risk factors evaluated included myometrial invasion, tumor grade, size, location, and cervical invasion. Univariate logistical regression models were applied to study any possible association of LVSI with these factors. Values were adjusted by multivariate logistic regression analysis.ResultsA total of 327 patients with endometrial carcinoma treated in our Centre were included. LVSI was observed in 120 patients (36.7%). Lower uterine segment involvement (OR 5.21, 95% CI:2.6–10.4, p < 0.001) and size ≥2 cm (OR 2.62, 95% CI: 1.14–6.1, p < 0.001) were independent factors for LSVI in multivariate analysis. In univariate analysis, LVSI was a surrogate marker in type 1 tumors with deep myometrial invasion (IB, 51.9% vs. IA, 16.0%; p < 0.001), grade 3 (G3 55.8% vs. G1 16.2%; p < 0.001), size ≥2 cm (37.9% vs. 16.1%, p = 0.005), those with involving the lower segment of the uterus (58.9% vs. 22.5%, p < 0.001) and/or with cervical stromal invasion (65.4% vs. 26.1%, p < 0.001), and in type 2 tumors (61.5% vs. 30.5%, p < 0.001). The use of uterine manipulator did not increase the rate of LVSI (35.5% vs. 40.5%, p = 0.612) as compared to no manipulator use.ConclusionsSize ≥2 cm and involvement of the lower uterine segment are independent factors for LSVI, in type 1 tumors, which can be used for surgical planning. LVSI is also more common in type 1 tumors with deep myometrial invasion, grade 3 and/or cervical stromal invasion, and also in type 2 tumors. The use of a uterine manipulator does not increase LVSI.     

The grading of lymphovascular space invasion in endometrial carcinoma

BACKGROUND: This study was conducted to elucidate the prognostic significance of a three-grade system for lymphovascular space invasion (LVSI). METHODS: The prognostic significance of the grading of LVSI as compared with other pathologic variables was evaluated in a study of 303 Japanese women with endometrial carcinoma. The criteria for determining the grade of LVSI were as follows: none (no LVSI), mild (a focus of LVSI was recognized around a tumor), and severe (diffuse or multifocal LVSI were recognized around the tumor or in the myometrium regardless of the degree of myometrial invasion). Both univariate and multivariate regression analyses were performed. The effects of different surgical methods and adjuvant therapies on survival were also examined. RESULTS: A univariate survival analysis showed that survival significantly correlated with surgical stage, histologic grade, depth of myometrial invasion, LVSI, cervical invasion, ovarian metastasis, and tubal metastasis. Of the three grades of LVSI, survival showed the most difference between the mild and severe groups. In multivariate analysis, the highest correlation with survival was observed for LVSI (P = 0.0008). Lymph node metastasis was also significantly associated with LVSI (P = 0. 0001). The correlation between histologic variables and survival was only slightly influenced by the differences in surgical methods and adjuvant therapies. CONCLUSIONS: The grading of LVSI was found to be an important histologic prognostic variable. The severe degree of LVSI also was found to be a good indicator of lymph node metastasis. It is therefore important to evaluate the grade of LVSI based on a histologic examination of at least one cut surface of the hysterectomy specimen that macroscopically shows the deepest myometrial invasion.     

Ploidy and S-phase fraction are correlated with lymphovascular space invasion that is predictive of outcomes in endometrial cancer

Background

Pathological detection of lymphovascular space invasion (LVSI) is a useful prognostic marker for patients with endometrial cancer. However, LVSI is criticized for its subjectivity and poor reproducibility. To improve the outcomes of patients with endometrial cancer, we evaluated objective parameters associated with LVSI to generate more accurate LVSI assessments and to identify patients with high-risk disease.

Methods

We reviewed the medical records of 137 patients with endometrial cancer. Flow cytometry was used to determine DNA ploidy and S-phase fraction. Estrogen and progesterone receptor (ER and PR) levels and p53 and k-ras mutational status were tested.

Results

LVSI was found in 36 patients (26.3%). Patients with LVSI had significantly decreased recurrence-free survival and overall survival compared to those without LVSI. Aneuploid tumors were significantly more frequent in LVSI-positive patients compared with LVSI-negative patients (odds ratio?=?5.208, P?<?0.001). With the exception of p53 mutational status, there was a statistically significant relationship between LVSI and other parameters tested. However, by multivariate analysis, DNA ploidy and S-phase fraction were significantly correlated with LVSI (P?=?0.034 and 0.001, respectively).

Conclusion

Ploidy and S-phase fraction correlate with LVSI, which is a significant independent predictor of clinical outcome in patients with endometrial cancer.     

Expression of cyclooxygenase-2 and inducible nitric oxide synthase correlates with tumor angiogenesis in endometrial carcinoma

The present study evaluated the significance of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in 30 patients with endometrial carcinoma and the relationship of those molecular markers to tumor characteristics and microvessel density (MVD). Immunohistochemical expression of COX-2, iNOS, and CD34 was analyzed on paraffin-embedded tissue sections. The COX-2 and iNOS positive rates were 66.7% and 73.3%, respectively. The level of COX-2 expression was higher in grade II tumors than in grade III tumors (p < 0.05). The percentage of iNOS positivity was higher in patients with deep myometrial invasion than in patients without or less than 50% myometrial invasion (p < 0.05). There was significant correlation between positive COX-2 and positive iNOS expression (r = 0.601, p < 0.001). Both COX-2 and iNOS were significantly correlated with MVD (r = 0.02 p < 0.05; r = 0.599 p < 0.0001, respectively). The present findings suggest that combined expression of COX-2 and iNOS may play an important role in development and invasion of endometrial cancer and that this could be partially attributable to modulation of angiogenesis by COX-2 and iNOS.     

Preoperative Monocyte Count as a Mirror of Tumor Characteristics and Likelihood of Recurrence in Endometrial Carcinoma Cases

Background: Recently preoperative hematologic parameters have attracted attention for their capacity to predicttumor characteristics and recurrence. Considering the established role of tumor-associated macrophages (TAM) in thetumor microenvironment, we evaluated the role of the preoperative monocyte count as a surrogate for TAM. Methods:We retrospectively reviewed 166 patients with histopathologically proven endometrial cancers from January 2011 toMarch 2015 and assessed any association of preoperative monocyte count with tumor characteristics and recurrence.Results: The majority of patients had tumors with the following characteristics: endometrioid histology (83.1%), lowgrade (grade I-II, 71.7%) and stage I disease (68.1%). The mean ± SD monocyte, neutrophil and platelet counts were 8.23x 109/L ± 3.56 x 109/L, 64.0 x 109/L ± 11.3 x 109/L and 261.6 x 109/L ± 74.6 x 109. Statistically significant associationswere noted with between preoperative monocyte count and tumor stage (p value=0.044), recurrence (p value<0.001) andomentum involvement (p value< 0.001) but not with tumor grade (p value=0.897), depth of myometrium involvement(p value=0.479), lymphovascular space invasion (p value=0.269) and lymph node involvement (p value=0.377).Conclusion: An elevated preoperative monocyte count is related to more aggressive tumors and a higher recurrencerate in patients with endometrial cancer.     

Cyclooxygenase-2 Expression in Cervical Squamous Cell Carcinoma: the Significance of Expression in Neoplastic Cells within the Lymphovascular Space

Background: Cyclooxygenase-2 (COX-2) activity is related to the development and progression of cervicalcancer. Previous studies have shown that COX-2 expression in early stage (stage IB-IIA) cervical squamous cellcarcinoma is associated with lymph node metastasis in tumors with lymphovascular space invasion (LVSI), andthat COX-2 expression may facilitate lymph node metastasis after LVSI occurs. In this study, we evaluatedwhether COX-2 expression of neoplastic cells within lymphovascular spaces (tumor emboli) would provideadditional prognostic information. Methods: Immunohistochemical stained slides for COX-2 on 150 cases ofstage IB-IIA cervical squamous cell carcinoma with LVSI were evaluated for expression of COX-2 in tumoremboli. Results were correlated with overall COX-2 expression of tumor and clinicopathologic features usingstatistical analysis. Results: Expression of COX-2 was detected in 49.3% of cases. Expression of COX-2 intumor emboli (LV-COX-2 expression) was identified in 61 cases (40.7%). LV-COX-2 expression was associatedwith high LVSI count (p<0.001) and had a marginal association with tumor COX-2 expression (p=0.050) andlymph node metastasis (p=0.063). In tumors showing high LVSI count, LV-COX-2 expression was an independentpredictor for lymph node metastasis (p=0.038, 95% CI=1.030-2.725) whereas tumor COX-2 expression (p=0.550)was not. Conclusion: Evaluation of COX-2 expression in tumor emboli may provide additional prognostic valuefor lymph node metastasis in cervical squamous cell carcinomas with a high LVSI count.     

Is Substantial Lymphovascular Space Invasion Prognostic for Clinical Outcomes in Type II Endometrial Cancer?

AimsSubstantial lymphovascular space invasion (LVSI) compared with none or focal LVSI is predictive of lymph node involvement and worse clinical outcomes in endometrioid-type endometrial carcinoma. We aimed to quantify the incidence of substantial LVSI in type II (clear cell and serous) endometrial cancer and correlate the extent of LVSI with clinical outcomes.Materials and methodsA retrospective review was conducted on type II endometrial cancer patients who underwent surgical management from July 2017 to December 2019 using the three-tier LVSI scoring system. Binary logistic regression and Cox regression were used to analyse predictors of lymph node involvement or survival outcomes, respectively. The Kaplan–Meier method and Log-rank test were used to analyse differences in locoregional disease-free survival (LR-DFS), distant metastasis disease-free survival (DM-DFS) and overall survival between patients with substantial versus none/focal LVSI.ResultsIn 79 patients with type II endometrial carcinoma, no LVSI, focal LVSI and substantial LVSI was present in 48.1%, 15.2% and 36.7% of patients, respectively. Lymph nodes were involved in 0.0% with no LVSI, 20.0% with focal LVSI and 60.0% with substantial LVSI (P < 0.001). The median follow-up was 22.2 months. In patients with none/focal versus substantial LVSI, the 2-year LR-DFS and DM-DFS rates were 91.5% versus 71.4% (P = 0.01) and 90.2% versus 63.8% (P = 0.005), respectively. On univariate analysis, myometrial invasion ≥50%, tumour size ≥3.6 cm, substantial versus none/focal LVSI, lymph node involvement and omission of adjuvant radiotherapy were significant predictors for worse LR-DFS and DM-DFS (P < 0.05).DiscussionSubstantial LVSI has a high incidence in type II pathology at our institution and predicts for lymph node involvement and worse clinical outcomes.     

Tumor Diameter for Prediction of Recurrence,Disease Free and Overall Survival in Endometrial Cancer Cases

Aims: To analyse the predictors of recurrence, disease free survival and overall survival in cases with endometrial cancer. Materials and Methods: A total of 152 women diagnosed with endometrial cancer were screened using a prospectively collected database including age, smoking history, menopausal status, body mass index, CA125, systemic disorders, tumor histology, tumor grade, lymphovascular space invasion, tumor diameter, cervical involvement, myometrial invasion, adnexal metastases, positive cytology, serosal involvement, other pelvic metastases, type of surgery, fertility sparing approach to assess their ability to predict recurrence, disease free survival and overall survival. Results: In ROC analyses tumor diameter was a significant predictor of recurrence (AUC:0.771, P<0.001). The optimal cut off value was 3.75 with 82% sensitivity and 63% specificity. In correlation analyses tumor grade (r=0.267, p=0.001), tumor diameter (r=0.297, p<0.001) and the serosal involvement (r=0.464, p<0.001) were found to significantly correlate with the recurrence. In Cox regression analyses when some different combinations of variables included in the model which are found to be significantly associated with the presence of recurrence, tumor diameter was found to be a significant confounder for disease free survival (OR=1.2(95 CI,1.016-1.394, P=0.031). On Cox regression for overall survival only serosal involvement was found to be a significant predictor (OR=20.8 (95 % CI 2.4-179.2, P=0.006). In univariate analysis of tumor diameter > 3.75 cm and the recurrence, there was 14 (21.9 %) cases with recurrence in group with high tumor diameter where as only 3 (3.4 %) cases group with smaller tumor size (Odds ratio:7.9 (95 %CI 2.2-28.9, p<0.001). Conclusions: Although most of the significantly correlated variables are part of the FIGO staging, tumor diameter was also found to be predictor for recurrence with higher values than generally accepted.     

Lipocalin 2 expression is associated with aggressive features of endometrial cancer

ABSTRACT: BACKGROUND: Increased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinicopathologic phenotype, angiogenesis, markers of epithelial-mesenchymal transition (EMT), and patient survival. METHODS: Immunohistochemical staining was performed using a human LCN2 antibody on a population-based series of endometrial cancer patients collected in Hordaland County (Norway) during 1981-1990 (n = 256). Patients were followed from the time of primary surgery until death or last follow-up in 2007. The median follow-up time for survivors was 17 years. Gene expression data from a prospectively collected endometrial cancer series (n = 76) and a publicly available endometrial cancer series (n = 111) was used for gene correlation studies. RESULTS: Expression of LCN2 protein, found in 49% of the cases, was associated with nonendometrioid histologic type (p = 0.001), nuclear grade 3 (p = 0.001), >50% solid tumor growth (p = 0.001), ER and PR negativity (p = 0.028 and 0.006), and positive EZH2 expression (p < 0.001). LCN2 expression was significantly associated with expression of VEGF-A (p = 0.021), although not with other angiogenesis markers examined (vascular proliferation index, glomeruloid microvascular proliferation, VEGF-C, VEGF-D or bFGF2 expression). Further, LCN2 was not associated with several EMT-related markers (Ecadherin, N-cadherin, P-cadherin, beta-catenin), nor with vascular invasion (tumor cells invading lymphatic or blood vessels). Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes. Patients with tumors showing no LCN2 expression had the best outcome with 81% 5-year survival, compared to 73% for intermediate and 38% for the small subgroup with strong LCN2 staining (p = 0.007). In multivariate analysis, LCN2 expression was an independent prognostic factor in addition to histologic grade and FIGO stage. CONCLUSION: Increased LCN2 expression is associated with aggressive features and poor prognosis in endometrial cancer.     

Clinical usefulness of color Doppler ultrasound in patients with endometrial hyperplasia and carcinoma

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Cyclooxygenase-2 and p53 expressions in endometrial cancer.

Cyclooxygenase-2 (COX-2) has been known to be related with various types of carcinoma, but we have insufficient knowledge about the association between COX-2 and endometrial cancer. Many have reported a close relationship between p53 expression and a poor prognosis in endometrial cancer, but it is unclear whether p53 is an independent prognostic factor. To clarify these uncertainties, we examined the expressions of COX-2 and p53 in endometrial cancer tissues. The study was carried on 152 endometrial cancer patients who had operation at Seoul National University Hospital. Paraffin-embedded tissue blocks were sectioned and immunostained using monoclonal anti-COX-2 and anti-p53 antibodies. Twenty-seven (17.8%) specimens stained as COX-2 positive. COX-2 positivity was more frequently observed in postmenopausal patients than in premenopausal patients (8.8% versus 25.0%; P = 0.009). However, COX-2 positivity did not show a statistically significant association with any other clinicopathologic characteristic (parity, body mass index, histotype, International Federation of Gynecology and Obstetrics stage, grade, lymph node metastasis, deep myometrial invasion, or p53 overexpression). Thirty-one (20.4%) specimens showed p53 overexpression and this was significantly correlated with an advanced stage (P = 0.001), poor differentiation (P < 0.001), lymph node metastasis (P = 0.012), and deep myometrial invasion (P < 0.001). Multivariate Cox regression analysis showed that advanced stage was an independent prognostic factor of survival, but p53 overexpression was not. COX-2 may be associated with endometrial cancer carcinogenesis during the postmenopausal period but not with tumor aggressiveness and p53 overexpression. The p53 overexpression was found to be strongly associated with endometrial cancer aggressiveness.     

Liquid‐based preparation for endometrial cytology—Usefulness for predicting the prognosis of endometrial carcinoma preoperatively

BACKGROUND:

The authors evaluated the applicability and usefulness of immunocytochemical staining for cyclin A, p53, estrogen receptor α (ER‐α), and progesterone receptor B (PR‐B) as a preoperative prognostic indicators for endometrial carcinoma using endometrial cytology with the liquid‐based cytology (LBC) method.

METHODS:

Cytologic specimens from 44 patients who had endometrial carcinoma were prepared with the LBC method. The results of immunocytochemical and immunohistochemical staining for cyclin A, p53, ER‐α, and PR‐B were compared with clinicopathologic parameters and prognosis.

RESULTS:

Patients who had positive results for cyclin A and p53 and negative results for ER‐α and PR‐B appeared to have unfavorable clinicopathologic characteristics, such as high‐grade histology, advanced clinical stage, lymphovascular space involvement (LVSI), and deeper myometrial invasion (MI), and had a poor prognosis. In contrast, patients who had positive results for ER‐α and PR‐B, and negative results for cyclin A and p53 had favorable characteristics, such well differentiated tumor, early clinical stage, negative LVSI, and less MI, and had a good prognosis. Immunostaining results from cytologic specimens obtained in the clinic and at surgery and from histologic specimens obtained at surgery were correlated positively.

CONCLUSIONS:

Consistent specimens that were prepared using the LBC method facilitated multiple immunocytochemical analyses. Endometrial cytology with the LBC method was useful for predicting the prognosis of patients with endometrial carcinoma before therapy. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Is frozen-section diagnosis a reliable guide in surgical treatment of stage I endometrial carcinoma?

Frozen-section diagnoses and paraffin-section diagnoses were compared in 154 patients in stage I endometrial adenocarcinoma. In 134 (87%) of the 154 patients (p < 0.001), a corresponding depth of myometrial invasion was found, and in 132 (85.7%) patients the same tumor grade was established (p < 0.001). Frozen-section diagnosis of stage I endometrial adenocarcinoma is reliable for estimation of the extent of disease and accurately identifies patients who require surgical staging.     

Lymph node metastasis and pattern of recurrence in clinically early stage endometrial cancer with positive lymphovascular space invasion

ObjectiveTo investigate the rate, predictors of lymph node metastasis (LNM) and pattern of recurrence in clinically early stage endometrial cancer (EC) with positive lymphovascular space invasion (LVSI).MethodsWomen with clinically early stage EC and positive LVSI 2005 to 2012 were identified. Kaplan-Meier curves and logistic regression models were used.ResultsOne hundred forty-eight women were identified. Of them, 25.7% had LNM (21.7% pelvic LNM, 18.5% para-aortic LNM). Among patients with LNM who had both pelvic and para-aortic lymphadenectomy, isolated pelvic, para-aortic and both LNM were noted in 51.4%, 17.1%, and 31.4% respectively. Age and depth of myometrial invasion were significant predictors of LNM in LVSI positive EC. Node positive patients had high recurrence rate (47% vs. 11.8%, p<0.05) especially distant (60.9% vs. 7.9%, p<0.001) and para-aortic (13.2% vs. 1.8%, p=0.017) recurrences compared to node negative EC. LNM was associated with lower progression-free survival (p=0.002) but not overall survival (p=0.73).ConclusionEC with positive LVSI is associated with high risk of LNM. LNM is associated with high recurrence rate especially distant and para-aortic recurrences. Adjuvant treatments should target prevention of recurrences in these areas.     

Survival and failure analysis in stage II endometrial cancer using the revised 1988 FIGO staging system

Fifty-one patients with Stage II endometrial carcinoma diagnosed between 1974 and 1987 were restaged according to the FIGO 1988 revisions for endometrial carcinoma. Patients were divided into Stage IIA, those patients with cervical glandular involvement without stromal invasion, and Stage IIB, those patients having stromal invasion of the cervix. Tumor grade was also assessed. Patients were treated with radiation therapy alone, pre-operative radiation therapy followed by a simple hysterectomy, or a simple hysterectomy followed by postoperative radiation therapy. The 5-year actuarial survival for Stage IIA was 86% and the 5-year actuarial survival for Stage IIB was 46% (p = 0.06). The 5-year local recurrence rate in each group was 9%. Stage IIA had a distant metastases rate of 14% whereas 44% of the patients in Stage IIB developed distant disease (p = 0.06) at 5 years. The grade of the tumor did not play a role in local recurrence. However, when tumor grade was analyzed with respect to distant disease, 14% of patients with grade 1 tumors developed distant metastases, 31% of patients with grade 2 tumors developed distant metastases, and most significantly, 63% of patients with grade 3 tumors developed distant metastases (p = 0.004). There was no statistically significant relationship between stromal invasion and tumor grade. This study concludes that grade is the greatest predictor of survival, with only 37% of grade 3 patients surviving at 5 years. As a predictor of survival, stromal invasion is of less significance than grade (p = 0.06 vs. p = 0.004). Death most often occurs because of distant metastases, and local failure is rare and is not dependent on the degree of cervical involvement or grade.     

Lymphvascular space involvement compromises the survival of patients with stage I endometrial cancer: results of a multicenter study.

AIMS: To quantify the relative risk associated with lymphvascular space involvement (LVSI) on outcome measures in patients with apparent stage I endometrial cancer. METHODS: Six hundred and ninety nine consecutive patients with endometrial carcinoma apparent stage I, who underwent surgery in one of four gynecological oncology centers in Israel, comprised the study population. Forty cases with and 659 without LVSI were followed for a median time of 39 months. Recurrence free, disease specific and overall survival was compared between the two groups. The effect of LVSI, adjusted for other clinical and histo-pathological prognostic factors, was assessed by multivariate analysis. RESULTS: The univariate Kaplan-Meier procedure for survival analysis showed that patients with LVSI had lower recurrence free survival (p=0.0003), worse disease specific (p=0.0007) and overall survival (p<0.0001). Cox proportional hazards model demonstrated a trend toward shorter recurrence free survival (HR=2.0, 95% CI 0.9, 4.5; p=0.08), a worse disease specific survival (HR=2.8, 95% CI 1.1, 7.4; p=0.04) and decreased overall survival (HR=2.0, 95% CI 1.1, 3.8; p=0.03) in cases with LVSI. CONCLUSIONS: In patients with apparent stage I endometrial cancer the presence of LVSI, an independent poor prognostic factor, is associated with a two fold increased risk of death. The presence of LVSI warrants consideration when deciding upon post operative management.     

Long-term outcome in endometrial carcinoma favors a two- instead of a three-tiered grading system

PURPOSE: Endometrial carcinoma is the most common malignancy of the female genital tract. Recognized prognostic factors include FIGO stage, histologic grade, depth of myometrial invasion, and age. Although determination of these factors may seem clear and reproducible, the histologic grade has recently been the subject of debate. A retrospective analysis of long-term outcome and predictive factors in endometrial carcinoma was conducted, focusing on the prognostic value of tumor grade. MATERIALS AND METHODS: The study included 253 patients with endometrial carcinoma Stages I to III, who were treated between 1984 and 1993. The histologic slides were reviewed and the prognostic value of stage, age, myometrial invasion (depth and pattern), tumor grade, and histologic subtype was analyzed. The end point was cancer-specific death; the median follow-up time was 11.7 years. RESULTS: The actuarial 5- and 10-year cancer-specific survival rates (CSS) were 85% and 82%, respectively. Five-year vaginal and/or pelvic recurrence and distant relapse rates were 7% and 15%. In multivariate analysis, stage, pattern of myometrial invasion, tumor grade, and age were independent prognostic factors. At pathology review, a shift from Grade 2 to Grade 1 was seen in 112 of the original 144 Grade 2 (78%). There was no difference in CSS between Grade 1 and Grade 2 (94 vs. 90% for original grade and 92 vs. 95% for grade after review), whereas Grade 3 was found to be a significant adverse prognostic factor (p < 0.001). CONCLUSIONS: The independent prognostic factors for patients with endometrial cancer were stage, pattern of myometrial invasion, tumor grade, and age. Systematic grading led to a considerable shift from Grade 2 to Grade 1. However, there was no difference in prognostic significance between Grade 1 and 2, whereas Grade 3 was a major adverse prognostic factor. A two-tiered grading system, instead of the currently used three-tiered system seems preferable, because it has a better correlation with clinical outcome and is expected to have less interobserver variability.