Prognostic Factor In Endometrial Cancer Research Articles

Cleaved caspase-3 expression is a potential prognostic factor for endometrial cancer with positive peritoneal cytology.

Positive peritoneal cytology (PPC) in endometrial cancer remains a controversial topic. Cleaved caspase-3 (CC3) and Ki-67 are excellent markers of apoptotic and proliferating cells, respectively. The objective of this study was to determine the significance of CC3 and Ki-67 expression in peritoneal cytology samples as prognostic factors for endometrial cancer with PPC. Sixty endometrial cancer specimens with PPC alone were divided into 51 endometrioid tumours (43 endometrioid carcinomas and eight carcinomas with squamous differentiation) and nine non-endometrioid tumours (two serous carcinomas, three clear cell carcinomas and four carcinosarcomas). CC3 and Ki-67 expression in peritoneal cytology samples were immunocytochemically assessed and correlated with disease-free survival (DFS) and overall survival (OS). Expression levels of CC3 and Ki-67 were not associated with any clinicopathological parameter. Patients with non-endometrioid tumours had significantly shorter DFS (P=.001) and OS (P=.001). Low CC3 expression (CC3Low ) was significantly associated with shorter OS (P=.02), but not DFS (P=.13). Multivariate analysis showed that non-endometrioid histology and CC3Low were independent prognostic factors. However, Ki-67 expression was not associated with survival. When endometrioid and non-endometrioid tumours were assessed separately, CC3Low was significantly associated with shorter DFS (P=.002) and OS (P=.002) in patients with non-endometrioid tumours. Our results suggest that CC3Low in peritoneal cytology samples is a poor prognostic factor in patients with endometrial cancers, especially non-endometrioid tumours. Immunocytochemical analysis of CC3 expression could potentially facilitate identification of patients with high-risk endometrial cancer with PPC.

Loss of RUNX3 is significantly associated with advanced tumor grade and stage in endometrial cancers.

Loss of runt-related transcription factor 3 (RUNX3) has been reported in various cancers, and one of the mechanisms mediating loss of RUNX3 expression is DNA methylation. However, the role of RUNX3 expression and its DNA methylation status as prognostic factors in endometrial cancer remain unclear. In the present study, the expression and promoter methylation of RUNX3 was examined in endometrial cancer tissues and cell lines, as well as their association with endometrial cancer prognosis. Fifty-five endometrial cancer tissues and two endometrial cancer cell lines (HEC1-α and Ishikawa) were studied. RUNX3 expression and promoter methylation were examined using reverse transcription-polymerase chain reaction (RT-PCR), methylation specific PCR (MS-PCR), and immunohistochemical staining. The demethylating agent 5-aza-2′-deoxycytidine (ADC) was used to reverse the methylation of the RUNX3 promoter. Loss of RUNX3 expression was observed in 50.9% (27/53) of endometrial cancer tissues and in the HEC1-α cell line by immunohistochemistry and RT-PCR, respectively. Methylation of the RUNX3 promoter was observed in 62.2% (33/53) of endometrial cancer tissues, 12.5% (1/8) of normal endometrial tissues, and the HEC1-α cell line by MS-PCR. Tumor grade and stage were significantly correlated with loss of RUNX3 expression. The expression of RUNX3 was restored by treatment with ADC and resulted in growth inhibition in HEC1-α cells. The present results suggested that methylation may serve a critical role in the silencing of RUNX3 and loss of RUNX3 expression may serve as a prognostic marker in endometrial cancer.

Significance of calreticulin as a prognostic factor in endometrial cancer.

In patients with endometrial cancer, the expression and prognostic significance of calreticulin (CRT) remains to be fully elucidated. To investigate the role of CRT in endometrial cancer, the present study compared its expression status with clinicopathological characteristics and evaluated its prognostic significance. The expression of CRT, PKR-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), and Ki67 were assessed by immunohistochemistry and/or western blotting in endometrial cancer patients. The association of the expression of CRT, p-eIF2α and Ki67 with patient survival rate was assessed by Kaplan-Meier and Cox regression analyses. Low levels of CRT and an overexpression of Ki67 were significantly associated with the stage, histology, and differentiation of the primary surgery without doxorubicin (DOX) neoadjuvant chemotherapy (NAC) patient group and were significantly correlated with a short progression-free survival and the overall survival. A multivariate analysis revealed that CRT and Ki67 expression were independent prognostic indicators for endometrioid endometrial cancer. Low CRT expression and an overexpression of Ki67 were significantly associated with DOX-NAC and the histology (P<0.05) pre-NAC and post-NAC in the DOX-NAC patient group. Upon treatment of DOX-NAC, CRT, PERK and p-eIF2α protein content were overexpressed in DOX-sensitive endometrial cancer (P<0.05), whereas there was no significant difference in the DOX-resistant group. Low CRT expression in endometrial cancer is significantly associated with aggressive progression and poor prognosis. CRT may therefore serve as a molecular marker for predicting the progression and prognosis in DOX-resistant endometrial cancer patients.

Preoperative Prediction of Lymph Nodal Metastases in Endometrial Carcinoma: Is it Possible?: A Literature Review.

Lymph node status is one of the most important prognostic factors in endometrial cancer and crucial for deciding adjuvant therapy. The aim of the study was to assess the different models used to predict lymphatic nodal disease. A literature search was conducted to detect the relevant studies. Relevant papers comparing the preoperative modality with the final histopathological results including randomized clinical trials, case-control studies, and any publications with a minimum of 50 patients in the report. Molecular-based predictors are still far from a practical application. Preoperative radiological scans (positron emission tomography, computed tomography, magnetic resonance imaging, and ultrasound) have shown the best predictor of lymphatic dissemination. However, there is currently no ideal model available, which can be used within standard clinical care. Surgical staging still remains the criterion standard in the determination of lymph node status in endometrial cancer.

The Effect of Adenomyosis in Myometrial Invasion and Overall Survival in Endometrial Cancer.

The aim of this study was to evaluate whether adenomyosis had an effect on myometrial tumor invasion, stage of the disease, and survival in endometrial cancer. Endometrial cancer patients encountered between 2007 and 2016 were identified from pathology records. Patients who underwent suboptimal surgical or medical treatment or with insufficient clinical or surgical data were excluded. Patients diagnosed as having concurrent adenomyosis constituted the study group. Control group patients were randomly selected in a paired design according to the tumor grades in the study group, and for each tumor grade, 4 times as many as patients were included. Tumor stage, histologic type and grade, myometrial invasion, lymphovascular space invasion, presence and location of the adenomyosis in myometrial wall, distance from endometrial line, tumor in adenomyosis, adjuvant treatment, and relapse were primary outcomes.Age, body mass index, medical comorbidities, and type of operation were also recorded. Univariate and multivariate Cox proportional hazards regression models were performed for overall survival. Of those 1242 endometrial cancer patients, 80 with concurrent adenomyosis were identified and compared with 320 patients without adenomyosis following a paired selection based on tumor grade. Higher rates of myometrial invasion, lymphovascular space invasion, tumor diameter, and adjuvant treatments were found in the nonadenomyosis group compared with adenomyosis group (P ≤ 0.001). In patients with adenomyosis, rates of early-stage disease and overall survival were significantly higher compared with the control group (P = 0.001 and 0.01, respectively). Our results showed that adenomyosis is significantly associated with lower stage in endometrial cancer that may suggest a possible limiting effect on endometrial cancer spread. In addition, despite similar rates in disease-free survival and endometrial cancer-related death, overall survival rate was significantly higher in the presence of adenomyosis and might be considered as a good prognostic factor for endometrial cancer.

Lymphatic vessel involvement is predictive for lymph node metastasis and an important prognostic factor in endometrial cancer.

Lymphovascular space involvement is reported to be an important risk factor in endometrial cancer. This study was conducted to evaluate the separate prognostic effects of lymphatic invasion and venous invasion on the outcomes of patients with endometrial cancer. From 2006 to 2013, 189 histologically confirmed endometrial cancer patients were examined. To study the venous invasion (v) of the endometrial cancer, Victoria blue-H&E staining-which positively stains the elastic fibers of vessels-was performed. Immunohistochemical staining with D2-40 was used to study the lymphatic invasion (ly) of the endometrial cancer. The median age of the patients was 57 (range 25-84) years. ly(+) and/or v(+) patients were significantly more likely to present an advanced cancer stage, G3 tumor, and deep myometrial invasion than ly(-)/v(-) patients. The incidence of lymph node metastasis was high in ly(+) patients, and that of ovarian metastasis was high in v(+) patients. Lymphatic vessel invasion was significantly correlated with regional lymph node metastasis. We found a significantly higher incidence of distant metastasis in ly(+) patients. Most recurrences in ly(+)/v(-) patients occurred in lymph nodes, while those in ly(+)/v(+) patients occurred mainly at distant organs. Finally, the prognosis was significantly poorer for ly(+) patients, in whom lymphatic invasion was an independent prognostic factor along with distant metastasis. Our study suggests that by separately evaluating lymphatic invasion and blood vessel invasion in endometrial cancer cases, useful information for predicting lymph node metastasis and recurrence sites as well as prognostic information can be obtained.

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

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&gt;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&lt;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.

Expression of neurotensin receptor 1 in endometrial adenocarcinoma is correlated with histological grade and clinical outcome.

The promalignant effects of neurotensin (NTS) are sustained in many solid tumors, including hormone-dependent cancers. As the endometrium is also subjected to hormonal regulation, we evaluated the contribution of NTS to endometrial carcinogenesis. Neurotensin receptor 1 (NTSR1) expression and NTSR1 promoter methylation (HM450) were analyzed in 385 cases of endometrial carcinoma from The Cancer Genome Atlas (TCGA). Additionally, from a series of 100 endometrial carcinomas, and 66 benign endometrium samples, NTS and NTSR1 labeling was evaluated by immunohistochemistry. Using TCGA series, NTSR1 messenger RNA (mRNA) level was negatively correlated with overall survival (OS) and progression-free survival (PFS) (p=0.0012 and p=0.0116, respectively), and positively correlated with the grade (p=0.0008). When including only endometrioid carcinomas, NTSR1 mRNA level continued to be negatively correlated with OS (log-rank: p<0.0001) and PFS (log-rank: p=0.002). A higher NTSR1 mRNA level was significantly associated with a loss of NTSR1 promoter methylation. Immunohistochemical expression of NTS and NTSR1 was significantly increased in adenocarcinoma (n=100), as compared to benign endometrium (p<0.001). NTSR1 expression was positively correlated with grade (p=0.004). High immunohistochemical expression of cytoplasmic NTSR1 was significantly correlated with a shorter OS and PFS (p<0.001 and p=0.001, respectively). This correlation remained significant when excluding non-endometrioid subtypes (p=0.04 and p=0.02, respectively). In multivariate analysis, the expression of NTSR1 was an independent prognostic factor (p=0.004). NTSR1 overexpression is a poor prognostic factor in endometrial cancer, highlighting the contribution of NTS in endometrial cancer progression and its uses as a prognostic marker, and as a potential therapeutic target.

Utility of Adult Comorbidity Evaluation 27 (ACE-27) in predicting survival of stage I endometrial cancer patients

Objective: Adult Comorbidity Evaluation 27 (ACE-27) is a validated tool that reflects the number and severity of medical comorbidity. ACE-27 is an independent prognostic factor for endometrial cancer (EC) patients after adjusting for stage, grade, histology, and adjuvant therapy. Our objective was to evaluate the impact of ACE-27 score on disease-specific survival (DSS) and overall survival (OS) in stage I EC patients.

Clinical importance of serum HE4 and MMP2 levels in endometrial cancer patients

IntroductionEndometrial cancer is the one of the most common cancers of the genital organ. HE4 and MMP2 are both proteins whose serum levels increase in endometrial cancer.AimTo explore the diagnostic potential of the serum levels of HE4 and MMP2 in patients with endometrial cancer and benign endometrial diseases. To assess the relationship between the serum levels of HE4 and MMP2 and the typical prognostic factors in patients with endometrial cancer.Materials and methodsIncluded in the study was a group of 112 patients presenting with bleeding abnormalities at the Pomeranian Medical University in years 2012–2016. Serum HE4 concentrations were measured using the Elecsys Electrochemiluminescence Immunoassay (ECLIA). MMP2 concentrations were quantified in the serum using multiplex immunoassays.ResultsWe observed statistically significant differences in mean serum levels of HE4 and MMP2 between the group of endometrial cancer patients and the group of patients with no changes in the endometrium (P=0.002/0.003). The diagnostic potential of HE4 and MMP2 in differentiation of high (International Federation of Gynecology and Obstetrics [FIGO] III and IV) vs low (FIGO I and II) clinical stage of tumor and prediction of cellular differentiation grade (G1 vs G3) on the basis of the analysis of the area under the curve is, respectively, 0.86 and 0.82 for HE4 and 0.82 and 0.74 for MMP2. The HE4 marker was significantly more specific than MMP2 in every study group and amounted to 93% vs 86% in all patients included in the analysis, 94% vs 84% in pre-menopausal patients and 84% vs 79% in post-menopausal patients.ConclusionHE4 and MMP2 are characterized by high specificity and may be useful as biomarkers in the diagnostics of endometrial cancer. When determined preoperatively, HE4 is correlated with the prognostic factors of endometrial cancer and may be helpful in the planning of individual treatment of endometrial cancer patients.

Sentinel Lymph Node Technique in Endometrial Cancer.

Endometrial cancer (EMCA) is the most common gynecologic malignancy, with an estimated 54,000 new cases and 10,000 deaths in the United States in 2015. Lymph node metastasis is the most significant prognostic factor in EMCA. Sentinel lymph node (SLN) mapping has become a well-accepted procedure in surgical oncology and may strike a balance between the risks and benefits of lymphadenectomy. The aim of this study was to review the current literature regarding the history, techniques, and clinical application of SLN mapping in EMCA. Evidence was obtained through systematic literature review through PubMed and ClinicalTrials.gov. Sentinel lymph node biopsy for EMCA is an accepted approach to the staging of this cancer; however, a consensus approach to the SLN biopsy technique and pathologic assessment is needed. Surgeons newly adopting the technique should proceed with caution and care to monitor outcomes.

Is lower uterine segment involvement a prognostic factor in endometrial cancer?

The purpose of this study is to investigate the prognostic significance of lower uterine segment (LUS) involvement in endometrial cancer (EC). We reviewed the patients who were operated at our institution between July 2007 and March 2015 with the diagnosis of EC. Tumors localized in the corpus and involving the LUS or localized entirely in the LUS formed Group A, while tumors in the uterine corpus without LUS involvement formed Group B. Clinicopathological characteristics and survival of the patients were compared in both groups. A total of 500 patients were included in the study. There were 139 patients who had tumors involving the LUS and formed Group A, while 361 patients with endometrial tumors in the uterine corpus without LUS involvement formed Group B. We did not detect a significant difference between survival of the patients in group A and group B (78 months vs. 87 months, respectively; P > 0.05). We found that LUS involvement was not an independent prognostic factor for poor survival, but it is associated with other poor prognostic factors such as deep myometrial invasion, uterine serosal involvement, lymphovascular space invasion, lymph node metastasis and higher FIGO grade.

Nucleophosmin/B23 is a negative regulator of estrogen receptor α expression via AP2γ in endometrial cancer cells.

Endometrial cancers expressing estrogen and progesterone receptors respond to hormonal therapy. The disappearance of steroid hormone receptor expression is common in patients with recurrent disease, ultimately hampering the clinical utility of hormonal therapy. Here, we demonstrate for the first time that nucleophosmin (NPM1/B23) suppression can restore the expression of estrogen receptor α (ESR1/ERα) in endometrial cancer cells. Mechanistically, B23 and activator protein-2γ (TFAP2C/AP2γ) form a complex that acts as a transcriptional repressor of ERα. Our results indicate that B23 or AP2γ knockdown can restore ERα levels and activate ERα-regulated genes (e.g., cathepsin D, EBAG9, and TFF1/pS2). Moreover, AP2γ knockdown in a xenograft model sensitizes endometrial cancer cells to megesterol acetate through the upregulation of ERα expression. An increased immunohistochemical expression of AP2γ is an adverse prognostic factor in endometrial cancer. In summary, B23 and AP2γ may act in combination to suppress ERα expression in endometrial cancer cells. The inhibition of B23 or AP2γ can restore ERα expression and can serve as a potential strategy for sensitizing hormone-refractory endometrial cancers to endocrine therapy.

HOTAIR in relation to epithelial-mesenchymal transition and cancer stem cells in molecular subtypes of endometrial cancer.

Endometrial cancer (EC) is a hormone-related disease, showing highly diverse features of ER/PR/HER2 status-based molecular subtypes. Long noncoding RNA (lncRNA) HOX antisense intergenic RNA (HOTAIR) has recently emerged as a key molecule in many cancers, triggering epithelial-mesenchymal transition (EMT)-mediated cancer stem cell (CSC) formation, but little is known about its significance in EC. Thus, we aimed to investigate the clinical significance of HOTAIR itself in different molecular subtypes of EC and possible links between HOTAIR, EMT and CSC-related markers. The study group included 156 consecutive, stage I-IV EC patients treated between 2000 and 2010. ER, PR and HER2 protein expression were examined by immunohistochemistry (IHC) on tissue microarrays. RT-qPCR was used to analyze the expression levels of HOTAIR, EMT-related genes - SNAIL and SLUG - and the CSCs marker CD133. Molecular subtypes, defined as ER/PR+HER2+, ER/PR+HER2-, ER-PR-HER2+ and ER-PR-HER2-, occurred in 40.2%, 52.3%, 4.7% and 1.9% of cases, respectively. The expression of HOTAIR did not differ between the subtypes, but high HOTAIR expression correlated with shorter overall survival (p = 0.04) in the entire group. The expression levels of HOTAIR, SNAIL, SLUG and CD133 were similar in defined EC molecular subtypes. Our data do not confirm the role of HOTAIR in EMT-mediated CSC formation in EC. Neither does the diversity of EC molecular subtypes influence these processes. But HOTAIR expression could serve as an independent prognostic factor in EC. The clinical importance of the above discoveries requires further studies.

Association of Serum HE4 with Primary Tumor Diameter and Depth of Myometrial Invasion in Endometrial Cancer Patients at Rajavithi Hospital.

Although there are no biomarkers that are routinely used in endometrial cancer (EC) management, many studies have found that serum human epididymis protein 4 (HE4) is superior to cancer antigen 125 (CA125) in the detection of EC. The correlation of HE4 with two prognostic factors for EC, primary tumor diameter (PTD) and depth of myometrial invasion (DMI) may be useful in identifying EC patients at high risk of lymphatic dissemination. To evaluate the correlation of serum HE4 with PTD and DMI in patients with EC. A cross-sectional study was conducted on 70 EC patients who were scheduled for elective surgery at Rajavithi Hospital between 1st September 2013 and 30th May 2014. Preoperative serum levels of HE4 and CA125 were investigated, and then gross measurement of PTD was taken and postoperative pathologic slides were reviewed for DMI including histologic types, grading and staging. Preoperative serum HE4 levels were strongly correlated with PTD (r=0.65, p<0.001) and moderately correlated with DMI (r=0.46, p<0.001). Moreover, serum HE4 levels were significantly elevated in EC patients with PTD >2 cm (p<0.001) and DMI > 50% (p=0.004). The performance of serum HE4 in identifying EC patients at low risk and high risk of lymph node metastasis was significantly better than that of CA125 (AUC 0.88 vs. 0.65, p=0.003). At an optimal cut-off value of 70 pM/L, serum HE4 had a sensitivity of 83.3% and a specificity of 80.0%. In EC patients, preoperative serum HE4 is significantly correlated with PTD and DMI. Serum HE4 levels could be useful in identifying endometrial cancer patients at high risk of lymphatic spread who would benefit from systemic lymphadenectomy at the cut-off value of 70 pM/L.

Multiple multiparity is a negative prognostic factor for endometrial cancer in Poland.

Nulliparity is one of the most important reproductive risk factors for endometrial cancer. It is still discussed whether multiparity implies a more favorable course of the disease and higher overall survival rates. The aim of the study was to analyze the effect of parity on the overall survival of endometrial cancer patients in Poland. A retrospective analysis of parity on survival rates was performed in 810 women treated surgically for endometrial cancer in a single referential center of gynecological oncology. Higher parity was shown to be associated with significantly lower survival rates (p=0.03). Parity turned out to be an independent prognostic factor of survival (HR 1.9). Multiple multiparous women were older at the time of surgery, more often presented with deep myometrial infiltration and with involvement of the cervical stroma and had higher clinical stages of the cancer (only according to FIGO 1988 classification). The group of multiple multiparous women was characterized by significantly lower recurrence rates. Multiple multiparous women significantly more often presented with lower educational level, more often were diagnosed with comorbidities and a history of other malignancies, while breast cancer and colon cancer were of lesser evidence in multiple multiparous endometrial cancer patients. Multiparity turns out to be an unfavorable prognostic factor of survival in Polish women. Unfavorable prognosis in endometrial cancer patients in this group is associated with interactions between risk factors and negative prognostic factors, i.e. the conditions of tumor growth, rather than with the nulliparity itself.

Clinic, pathologicand biologic prognostic factors in endometrial cancer. A literature review.

Endometrial cancer (EC) is the most common gynecological malignancy in western countries which primarily affects postmenopausal women. The aim of this review is to outline the most important clinic, pathologic and biologic prognostic parameters in order to obtain the treatment outcomes in EC. Medline and Pubmed were searched for English language articles using keywords (i.e. “endometrial cancer”, “prognostic factors”). systematic reviews, retro-prospective studies, controlled and randomized clinical trials focused on prognostic information were selected. Bibliographies of articles found were searched for further relevant titles. The most significant reported prognostic factors are age, International Federation of Obstetrics and Gynecology stage, the histological subtype and grade of the tumor, peritoneal cytology, lymphovascular space involvement, invasion of the myometrum, tumors that extend to the cervical stroma,extra-uterine disease,tumor size,as well as the presence and extent of lymph node metastasis. Molecular biomarkers such as mutations in tumor suppressor genes, deoxyribonucleic acid mismatch repair, and the presence of a triple negative phenotype are considered worse prognostic factors, and may lead to a poor survival.

Do Leukocyte and Platelet Counts Have Benefit for \Preoperative Evaluation of Endometrial Cancer?

The aim of this study was to investigate the association between preoperative leukocyte and platelet counts and the stage of the disease in patients with endometrial cancer. Data for 100 patients undergoing total abdominal hysterectomy and bilateral salpingoophorectomy for benign uterine diseases and 177 patients surgically staged for endometrial cancer at Ondokuz Mayis University, Department of Gynecology and Obstetrics between 2005 and 2013, with preoperative complete blood count in the week prior to surgery including WBC, platelet count, pathologic evaluation for both benign and malign endometrium lesions, tumor stage and presence of lymphovascular space invasion (LVI), were retrospectively analyzed. The preoperative leukocyte count was significantly higher in patients with endometrial cancer when compared to the patients with benign diseases. However, there were no significant differences in platelet counts between the groups. Patients with advanced stage endometrial cancer had higher preoperative leukocyte counts when compared to the early stage disease whereas there was no difference in platelet count. Multivariate regression analysis identified preoperative leukocytosis as an independent prognostic factor for endometrial cancer. The optimal cut-off point for WBC was calculated as 10,500 to differentiate stage 1-2-3 and 4 with 88.9% sensitivity and 86.3% specificity (AUC: 0.901, 95% CI: 0.829-0.973, p<0.001, PPV: 25.8%, NPV: 99.3%). Preoperative leukocytosis is independently associated with advanced endometrial cancer.

Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer – A pooled analysis of PORTEC 1 and 2 trials

BackgroundLymph-vascular space invasion (LVSI) is an important adverse prognostic factor in endometrial cancer (EC). However, its role in relation to type of recurrence and adjuvant treatment is not well defined, and there is significant interobserver variation. This study aimed to quantify LVSI and correlate this to risk and type of recurrence. MethodsIn the post operative radiation therapy in endometrial carcinoma (PORTEC)-trials stage I EC patients were randomised to receive external beam radiotherapy (EBRT) versus no additional treatment after surgery (PORTEC-1, n=714), or to EBRT versus vaginal brachytherapy (PORTEC-2, n=427). In tumour samples of 926 (81.2%) patients with endometrioid tumours LVSI was quantified using 2-, 3- and 4-tiered scoring systems. Cox proportional hazard models were used for time-to-event analysis. ResultsAny degree of LVSI was identified in 129 cases (13.9%). Substantial LVSI (n=44, 4.8%) using the 3-tiered approach had the strongest impact on the risk of distant metastasis (hazard ratio (HR) 4.5 confidence interval (CI) 2.4–8.5). In multivariate analysis (including: age, depth of myometrial invasion, grade, treatment) substantial LVSI remained the strongest independent prognostic factor for pelvic regional recurrence (HR 6.2 CI 2.4–16), distant metastasis (HR 3.6 CI 1.9–6.8) and overall survival (HR 2.0 CI 1.3–3.1). Only EBRT (HR 0.3 CI 0.1–0.8) reduced the risk of pelvic regional recurrence. ConclusionsSubstantial LVSI, in contrast to focal or no LVSI, was the strongest independent prognostic factor for pelvic regional recurrence, distant metastasis and overall survival. Therapeutic decisions should be based on the presence of substantial, not ‘any’ LVSI. Adjuvant EBRT and/or chemotherapy should be considered for stage I EC with substantial LVSI.

Utility of tumor marker HE4 as prognostic factor in endometrial cancer: a single-center controlled study.

This study aims to investigate the correlation between preoperative human epididymis protein 4 (HE4) levels, endometrial cancer (EC) staging, and ideal cutoff for stage prediction. All EC patients, treated within January 2009 and February 2014 at the Division of Gynaecologic Oncology of the University Campus Bio-Medico of Rome, were considered for the study. For the first part of the study, we consider an HE4 cutoff of 70 pmol/L. Histotypes (endometrioid versus non-endometrioid), grading (G1, G2, G3), and stage were correlated with HE4 levels. In the second part of the study, the logistic regression was performed in stepwise mood to identify the ideal HE4 cutoff for stage prediction. Two hundred thirty-two patients with surgically staged EC and preoperative HE4 dosage were included in the study. We found that higher HE4 levels correlate with undifferentiated grading (p < 0.05). Moreover, we found that 42, 77, 90, 93 and 100 % of patients classified as International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, II, III, and IV, respectively, presented HE4 levels above the standard cutoff of 70 pmol/L. Based on receiver operating characteristic (ROC) curves, we found the ideal HE4 cutoff as follows: 61.3 pmol/L for FIGO stage IA (sensitivity = 82.3 % and specificity = 96 %), 89.2 pmol/L for FIGO stage IB (sensitivity = 83.3 % and specificity = 96 %), 104.3 pmol/L for FIGO stage II (sensitivity = 80.9 % and specificity = 98.6 %), 152.6 pmol/L for FIGO stage III (sensitivity = 92.5 % and specificity = 98.6 %), and 203.8 pmol/L for FIGO stage IV (sensitivity = 81.8 % and specificity = 99.3 %). Our results suggest a potential role of HE4 in EC stage prediction.