Prognostic Indicator For Endometrial Cancer Research Articles

TOMM40 Correlates with Cholesterol and is Predictive of a Favorable Prognosis in Endometrial Carcinoma.

A link between cholesterol and endometrial cancer has been established, but current studies have been limited in their findings. We aimed to elucidate the causal relationship between cholesterol and endometrial cancer and to find prognostic genes for endometrial cancer. We first explored the causal relationship between total cholesterol and endometrial cancer using two-sample Mendelian randomization and then obtained differential genes to screen for prognosis-related genes in endometrial cancer. Then, we utilized pan-cancer analysis based on RNA sequencing data to evaluate the expression pattern and immunological role of the Translocase of Outer Mitochondrial Membrane 40 (TOMM40). Through multiple transcriptome datasets and multi-omics in-depth analysis, we comprehensively explore the relationship of TOMM40 expression with clinicopathologic characteristics, clinical outcomes and mutations in endometrial cancer. Lastly, we systematically associated the TOMM40 with different cancers from immunological properties from numerous perspectives, such as immune cell infiltration, immune checkpoint inhibitors, immunotherapy, gene mutation load and microsatellite instability. We found a negative association between cholesterol and endometrial cancer. A total of 78 genes were enriched by relevant single nucleotide polymorphisms (SNPs), of which 12 upregulated genes and 5 downregulated genes in endometrial cancer. TOMM40 was found to be a prognostic gene associated with endometrial cancer by prognostic analysis. TOMM40 was found to be positively correlated with the infiltration of most immune cells and immunization checkpoints in a subsequent study. Meanwhile, TOMM40 also was an oncogene in many cancer types. High TOMM40 was associated with lower genome stability. The findings of our study indicate that the maintenance of normal total cholesterol metabolism is associated with a decreased risk of developing endometrial cancer. Moreover, TOMM40 may have potential as a prognostic indicator for endometrial cancer.

Prognostic values of human epididymis protein 4 expression in patients with endometrial cancer: A systematic review and meta-analysis.

There is no consensus on the correlation between human epididymis protein 4 (HE4) and prognosis of endometrial cancer (EC). Therefore, we performed a meta-analysis to assess the relationship between HE4 and prognosis of EC. In this systematic review and meta-analysis, the databases were searched. Correlation of serum or tissue HE4 with clinicopathological characteristics was determined by odds ratio (OR) or standardized mean difference (SMD) with 95% confidence interval (CI), respectively. The hazard ratio (HR) with 95% CI was calculated to evaluate the correlation between HE4 and survival outcome. A total of 38 published studies were eligible. We found that high levels of serum HE4 were associated with FIGO III-IV stage (SMD=1.58, 95%CI: 1.18-1.98, p < 0.001), grade 3 (SMD=0.66, 95%CI: 0.39-0.93, p=0.001), ≥50% myometrial invasion (SMD=0.78, 95%CI: 0.58-0.99, p < 0.001), lymphovascular space invasion (SMD=0.82, 95%CI: 0.54-1.11, p=0.001), lymph node metastasis (SMD=1.27, 95%CI: 0.84-1.69, p < 0.001), cervical involvement (SMD=0.71, 95%CI: 0.43-0.98, p=0.003), parametrial involvement (SMD=1.03, 95%CI: 0.71-1.35, p < 0.001) and peritoneal cytology (SMD=0.49, 95%CI: 0.22-0.75, p < 0.001). High expression of tissue HE4 was only significantly associated with lymph node metastasis (OR=6.19, 95%CI: 2.07-18.50, p=0.001). High levels of serum HE4 were significantly associated with poor overall survival (univariate: HR=3.77, 95%CI: 1.94-7.32, p < 0.001; multivariate: HR=2.15, 95%CI: 1.65-2.80, p < 0.001) and disease-free survival (univariate: HR=2.89, 95%CI: 2.14-3.88, p < 0.001; multivariate: HR=2.31, 95%CI:1.20-2.67, p < 0.001) in EC. Compared with cancer antigen 125, serum HE4 may be a better prognostic indicator for EC. High HE4 expression is associated with poor prognosis of EC and may be a potential prognostic biomarker for EC.

Intraepithelial lymphocytes are indicators of better prognosis in surgically resected endometrioid-type endometrial carcinomas at early and advanced stages

BackgroundTumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) may be useful prognostic indicators in endometrial cancer. However, standardized assessment methods and the prognostic roles of these cells in different stage groups are unclear.MethodsFormalin-fixed paraffin-embedded tissue samples of 107 endometrioid-type endometrial carcinomas (EECs) comprising 60 stage IB and 47 stage IIIC or IVB cases were evaluated. CD3+ TILs, CD8+ TILs, CD68+ TAMs, and CD163+ TAMs were detected by immunohistochemistry, and their densities were evaluated by semiquantitative and quantitative methods. TILs within tumor epithelial cell nests (E-TILs) and those within the stroma at the invasive front (S-TILs) were evaluated separately for CD3+ and CD8+ cells. The “TIL score” was defined as the sum of semiquantitative scores of CD3+ E-TILs, CD3+ S-TILs, CD8+ E-TILs, and CD8+ S-TILs. For TAMs, the area of CD68+ and CD163+ cells in the invasive margin were semiquantitatively and quantitatively evaluated. Clinicopathological and prognostic implications of TILs and TAMs in stage IB and IIIC/IVB EECs were examined by Cox univariate and multivariate analyses.ResultsBy Cox univariate analyses, semiquantitatively low CD3+ E-TILs, low CD8+ E-TILs, and low “TIL score” were significantly correlated with worse prognosis in stage IB patients (P = 0.011, 0.040, and 0.039, respectively). Likewise, low CD3+ E-TILs and low CD8+ E-TILs, by both semiquantitative (P = 0.011 and 0.0051) and quantitative evaluations (P < 0.0001, and P = 0.0015) and low “TIL score” (P = 0.020) were significantly correlated with worse prognosis in stage IIIC/IVB patients. By Cox multivariate analyses, semiquantitatively low CD3+ E-TILs and low CD8+ E-TILs, low “TIL score”, and quantitatively low CD3+ E-TILs and low CD8+ E-TILs were independent worse prognostic factors in stage IIIC/IVB (P = 0.0011, 0.0053, 0.012, < 0.0001, and < 0.0001, respectively). CD68+ or CD163+ TAMs were not correlated with prognosis in any patients.ConclusionsBoth semiquantitatively and quantitatively low E-TILs, are correlated with worse prognosis in both early and advanced stage patients with EECs. In particular, CD3+ E-TILs and CD8+ E-TILs are potentially useful prognostic markers in patients with EEC regardless of the stage.

Markers of Lymphocytic-Macrophagal Infiltration and Their Association With the Receptor Phenotype and Proliferative Activity of Tumor Tissue in Various Molecular-Biological Types of Endometrial Cancer

Background and Aims: The last years were characterized by a shift from the former subdivision of endometrial cancer (EC) into two main types [1, 2] to modern molecular biological classifications of this disease [3-5]. The purpose of this investigation was an attempt to compare such prognostic indicators for EC as features of lymphocytic [6] and macrophage infiltration of tumor tissue with markers of its hormonal sensitivity (receptor phenotype) and the proliferation index Ki-67 [7], taking into account the molecular biological type of the disease. Materials and Methods: The study involved material from untreated patients with endometrial cancer (a total of 219 people). The average age of patients was close to 55-60 years. Using classification of Talhouk et al. [5] allowed to perform a search for POLE mutations, evaluate by IHC the expression of the oncoprotein p53 and MMR (mismatch-repair) proteins /MLH1, MSH2, MSH6 and PMS2/, and also identify the type of disease without a characteristic molecular profile (WCMP). The IHC method was also used to study the rate of estrogen (ER) and progesterone (PR) receptors, Ki-67 proliferative activity index, as well as the severity of macrophage-lymphocytic tissue infiltration of EC based on the analysis of the macrophage (CD68) and lymphocytic cells (cytotoxic CD8 and regulatory FoxP3) markers using reagents from Ventana and Dako. Statistical assessment of the relationships of the studied indicators was carried out by the Spearman rank correlation coefficient. Results: FoxP3 (in contrast to CD8 and CD68) positively and significantly correlates (ρ varies from 0.2895 to 0.3477) more often with ER, but not with PR. Ki-67 index in EC tissue positively and reliably correlates with FoxP3 both in the MMR-D and WCMP groups and in the combined cohort of EC patients. In the latter case, a similar relationship with Ki-67 extends to other studied markers of lymphocytic-macrophage infiltration, namely CD8 and CD68 (ρ 0,1746-0,3294). Only in the entire group of EC patients there is a positive rank correlation (0.4119!) between ER and PR expression. Conclusions: In patients with certain types of EC the connection between the estrogenic signal and PR induction is lost; it is especially noticeable in the MMR-D group, as exemplified by the negative correlation (-0.2951) of FoxP3 and PR expression. Taken together with existing data this indicates an important role of the endocrine component for differentiating separate groups of patients with EC, that may also be of practical importance.

Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Markers in Endometrial Cancer.

Background: Endometrial cancer (EC) is a major gynecologic adenocarcinoma that arises from the endometrium. While the incidence of EC is on the rise worldwide, survivorship and clinical advancement have considerably lagged compared to other cancers. Given the sensitive nature of the endometrium and its high expression of hormone receptors, hormonal therapy has become a favorable alternative treatment compared to highly toxic chemotherapeutics and radiation therapy.Methods: Clinical samples from patients diagnosed with EC were obtained. ER and PR staining were performed according to the S-P kit, and HER2 staining was carried out according to the UltrasensitiveTM S-P immunohistochemistry kit protocol. Chi-square analysis was conducted using the SPSS. P-values of less than 0.05 were taken as an a priori value for statistical significance.Results: Immunohistochemical (IHC) analysis showed the overall positive expression rates of ER, PR, and HER2 to be 59.8%, 75.0%, and 71.1%, respectively. Significant co-expression was found among all three receptors, suggesting a cooperative, synergistic effect. More importantly, we found that ER expression was correlated with FIGO staging and cervical invasion, whereas PR expression was associated with histologic type. No clinicopathologic features were correlated with HER2 expression, but HER2 positivity was inversely associated with the degree of HER2 overexpression.Conclusions: These results suggest that EC is a heterogeneous disease that may not conform to traditional, prototypically defined subtypes. The status of ER, PR, and HER2 receptors may have the potential to serve as prognostic indicators for EC, but further analysis is needed to ascertain their prognostic significance.

Serum carcinoembryonic antigen as a tumour marker in patients with endometrial cancer.

No potential tumour markers have been validated for prognosis in endometrial cancer. However, carcinoembryonic antigen (cea) is one of the most widely used tumour markers in various types of cancer. Although cea expression in endometrial cancer has been investigated, its prognostic value remains controversial, and no studies have investigated serum cea levels in large case series. In the present study, we investigated diagnostic and prognostic applications of serum cea for endometrial cancer. This prospective study was approved by our Institutional Review Board. Between January 2006 and December 2012, serum cea was measured prospectively in 215 patients with endometrial cancer and was subsequently measured during treatment and at scheduled follow-up examinations in patients with elevated baseline serum cea. During the study period, 215 patients (142 stage i, 19 stage ii, 32 stage iii, 22 stage iv) were treated for endometrial cancer. By the time of last follow-up, 52 had relapsed (24.2%), and the median follow-up duration was 45 months (range: 1-95 months). Elevated serum cea was identified in 25 patients (11.6%) and was associated with histologic type (p = 0.04), histologic grade (p = 0.03), and myometrial invasion depth (p = 0.01). Elevated serum cea was not related to clinical stage, lymph node metastasis, distant metastasis, age, menopausal status, or body mass index. Relapse of disease was related to elevated serum cea (p = 0.006). Serum cea is a potential prognostic indicator for endometrial cancer.

Serum Sialyl-Tn (STN) as a Tumor Marker in Patients with Endometrial Cancer.

There are no potential tumor markers validated for prognosis of endometrial cancer. However, sialyl Tn (STN) is a carbohydrate antigen that is associated with the production of mucin, which reportedly plays important roles in carcinogenesis. Although STN expression in endometrial cancer has been investigated, its prognostic value remains controversial and no studies have investigated serum STN levels in large case series. In this study, we investigated diagnostic and prognostic applications of serum STN for endometrial cancer. Between January 2006 and December 2012, serum STN levels were examined prospectively in patients with endometrial cancer. A total of 146 patients (stage I, 98; stage II, 15; stage III, 17; stage IV, 16) were treated for endometrial cancer. The median age was 60years (28-83). Subsequently 29 patients (19.9%) relapsed at the time of the last follow-up and the median follow-up time was 44months (1-83). Elevated serum STN levels were identified in 36 patients (24.7%) and were associated with histological grade (p = 0.02) and lymph node metastasis (p = 0.006). Elevated serum STN levels were not related to histological types, clinical stages, myometrial invasions, distant metastases, age, menopausal status, body mass index, or relapse. Among the 36 patients with elevated serum STN levels, 33 (91.7%) achieved remission and serum STN levels returned to the normal range. Seven patients (21.2%) with elevated serum STN levels at baseline relapsed and their serum STN levels were again elevated. Serum STN levels are a potential prognostic indicator for endometrial cancer.

The prognostic significance of tumour-stroma ratio in endometrial carcinoma.

BackgroundHigh tumour stromal content has been found to predict adverse clinical outcome in a range of epithelial tumours. The aim of this study was to assess the prognostic significance of tumour-stroma ratio (TSR) in endometrial adenocarcinomas and investigate its relationship with other clinicopathological parameters.MethodsClinicopathological and 5-year follow-up data were obtained for a retrospective series of endometrial adenocarcinoma patients (n = 400). TSR was measured using a morphometric approach (point counting) on digitised histologic hysterectomy specimens. Inter-observer agreement was determined using Cohen’s Kappa statistic. TSR cut-offs were optimised using log-rank functions and prognostic significance of TSR on overall survival (OS) and disease-free survival (DFS) were determined using Cox Proportional Hazards regression analysis and Kaplan-Meier curves generated. Associations of TSR with other clinicopathological parameters were determined using non-parametric tests followed by Holm-Bonferroni correction for multiple comparisons.ResultsTSR as a continuous variable associated with worse OS (P = 0.034) in univariable Cox-regression analysis. Using the optimal cut-off TSR value of 1.3, TSR-high (i.e. low stroma) was associated with worse OS (HR = 2.51; 95 % CI = 1.22–5.12; P = 0.021) and DFS (HR = 2.19; 95 % CI = 1.15–4.17; P = 0.017) in univariable analysis. However, TSR did not have independent prognostic significance in multivariable analysis, when adjusted for known prognostic variables. A highly significant association was found between TSR and tumour grade (P < 0.001) and lymphovascular space invasion (P < 0.001), both of which had independent prognostic significance in this study population.ConclusionsLow tumour stromal content associates with both poor outcome and with other adverse prognostic indicators in endometrial cancer, although it is not independently prognostic. These findings contrast with studies on many - although not all - cancers and suggest that the biology of tumour-stroma interactions may differ amongst cancer types.

Preoperative neutrophil:lymphocyte and platelet:lymphocyte ratios predict endometrial cancer survival

Background:Variations in systemic inflammatory response biomarker levels have been associated with adverse clinical outcome in various malignancies. This study determined the prognostic significance of preoperative neutrophil:lymphocyte (NLR), platelet:lymphocyte (PLR) and monocyte:lymphocyte (MLR) ratios in endometrial cancer.Methods:Clinicopathological and 5-year follow-up data were obtained for a retrospective series of surgically treated endometrial cancer patients (n=605). Prognostic significance was determined for overall (OS) and cancer-specific survival (CSS) using Cox proportional hazards models and Kaplan–Meier analysis. Receiver–operator characteristic and log-rank functions were used to optimise cut-offs. NLR, PLR and MLR associations with clinicopathological variables were determined using non-parametric tests.Results:Applying cut-offs of ⩾2.4 (NLR), ⩾240 (PLR) and ⩾0.19 (MLR), NLR and PLR (but not MLR) had independent prognostic significance. Combining NLR and PLR scores stratified patients into low (NLR-low and PLR-low), intermediate (NLR-high or PLR-high) and high risk (NLR-high and PLR-high) groups: multivariable hazard ratio (HR) 2.51; P<0.001 (OS); HR 2.26; P<0.01 (CSS) for high vs low risk patients. Increased NLR and PLR were most strongly associated with advanced stage (P<0.001), whereas increased MLR was strongly associated with older age (P<0.001).Conclusion:Both NLR and PLR are independent prognostic indicators for endometrial cancer, which can be combined to provide additional patient stratification.

929P - Serum Sialyl-Tn (Stn) As a Tumor Marker in Patients with Endometrial Cancer

There are no potential tumor markers validated for prognosis of endometrial cancer. However, sialyl Tn (STN) is a carbohydrate antigen that is associated with the production of mucin, which reportedly plays important roles in carcinogenesis. Although STN expression in endometrial cancer has been investigated, its prognostic value remains controversial and no studies have investigated serum STN levels in large case series. In this study, we investigated diagnostic and prognostic applications of serum STN for endometrial cancer. Between January 2006 and December 2012, serum STN levels were examined prospectively in patients with endometrial cancer. A total of 146 patients (stage I, 98; stage II, 15; stage III, 17; stage IV, 16) were treated for endometrial cancer. The median age was 60 years (28–83). Subsequently 29 patients (19.9%) relapsed at the time of the last follow-up and the median follow-up time was 44 months (1–83). Elevated serum STN levels were identified in 36 patients (24.7%) and were associated with histological grade (p = 0.02) and lymph node metastasis (p = 0.006). Elevated serum STN levels were not related to histological types, clinical stages, myometrial invasions, distant metastases, age, menopausal status, body mass index, or relapse. Among the 36 patients with elevated serum STN levels, 33 (91.7%) achieved remission and serum STN levels returned to the normal range. Seven patients (21.2%) with elevated serum STN levels at baseline relapsed and their serum STN levels were again elevated. Serum STN levels are a potential prognostic indicator for endometrial cancer.

Inverse Correlation between Tumoral Indoleamine 2,3-Dioxygenase Expression and Tumor-Infiltrating Lymphocytes in Endometrial Cancer: Its Association with Disease Progression and Survival

Tumor escape from host immune systems is a crucial mechanism for disease progression. We recently showed that the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) is a prognostic indicator for endometrial cancer. The purpose of the present study was to investigate the relationship between IDO expression and tumor-infiltrating lymphocytes (TIL) or natural killer (NK) cells and to clarify their prognostic effect in endometrial cancer. Immunohistochemical staining for IDO expression in endometrial cancer tissues (n = 65) was done. Tumor-infiltrating CD3+ and CD8+ lymphocytes, as well as CD57+ NK cells, were counted in serial tissue sections. High IDO expression in tumor cells was found in 32 of 65 cases and was positively correlated with myometrial invasion, nodal metastasis, and lymph-vascular space involvement. We also found a significant correlation between high IDO expression and reduced numbers of CD3+, CD8+, and CD57+ cells infiltrating into both the tumor epithelium and stroma. Patients with high IDO expression, a low number of stromal CD3 (<60), low intraepithelial CD8 (<25), or low stromal CD8 (<40) had significantly impaired progression-free survival. On multivariate analysis, IDO expression and the number of stromal CD3+ TILs were independent prognostic factors for impaired progression-free survival. Tumoral IDO expression correlated with a reduced number of TILs and NK cells in endometrial cancer, possibly contributing to disease progression and impaired clinical outcome. These findings suggest that targeting IDO to restore host antitumor immunity may be a therapeutic strategy for endometrial cancer.

Indoleamine 2,3-dioxygenase is a novel prognostic indicator for endometrial cancer

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolising enzyme inducing immune tolerance. The present study aimed to investigate IDO expression and its prognostic significance in endometrial cancer. Indoleamine 2,3-dioxygenase expression in endometrial cancer tissues (n=80) was immunohistochemically scored as four groups (IDO−, 1+, 2+, and 3+). The high IDO expression (IDO2+ or 3+) in tumour cells was found in 37 (46.3%) of the 80 cases, and was positively correlated with surgical stage, myometrial invasion, lymph-vascular space involvement, and lymph node metastasis, but not with the histological grade. Patients with high IDO expression had significantly impaired overall survival and progression-free survival (PFS) (P=0.002 and P=0.001, respectively) compared to patients with no or weak expression of IDO (IDO− or 1+). The 5-year PFS for IDO−/1+, 2+, and 3+ were 97.7, 72.9, and 36.4%, respectively. Even in patients with early-stage disease (International Federation of Gynecology and Obstetrics I/II, n=64), the PFS for IDO2+/3+ was significantly poor (P=0.001) compared to that for IDO−/1+. On multivariate analysis, IDO expression was an independent prognostic factor for PFS (P=0.020). These results indicated that the high IDO expression was involved in the progression of endometrial cancer and correlated with the impaired clinical outcome, suggesting that IDO is a novel and reliable prognostic indicator for endometrial cancer.

Correlation of presenting symptoms and patient characteristics with endometrial cancer prognosis in Japanese women

Objective To determine whether patient characteristics and presenting symptoms could be prognostic indicators for endometrial cancer in Japanese women. Methods Review of the medical charts, which included presenting symptoms and other patient characteristics, of 242 women who underwent surgical treatment for FIGO stage I–IV endometrial cancer. Results FIGO stage, histologic grade, and lower abdominal pain were found to be significant independent factors for progression-free and overall survival. In contrast, abnormal uterine bleeding, comorbidities, and prior malignancy were not found to be prognostic factors. Conclusion Lower abdominal pain was found to be an independent prognostic factor in endometrial cancer among Japanese women.

Positive Peritoneal Cytology in Endometrial Cancer: Enhancement of Other Prognostic Indicators

Objective. The goal of this study was to investigate the prognostic significance of positive peritoneal cytology in endometrial cancer.Methods. A clinicocytopathological study was performed in 534 patients with endometrial cancer to assess the prognostic value of positive peritoneal cytology. The study population was divided into three groups: a low-risk group (disease limited to the uterus, grade 1, and depth of invasion ≦1/2), a moderate-risk group (disease limited to the uterus, grade 2 or 3, and/or depth of invasion >1/2), and a high-risk group (extrauterine disease). In each group, disease-free survival was compared in the patients who were positive or negative for malignant cells.Results. The overall incidence of positive peritoneal cytology was 22.3% (119/534). The 5-year disease-free survival of patients positive or negative for malignant cells was 98.1% versus 100% in the low-risk group (n = 250), 77.5% versus 91.3% in the moderate-risk group (n = 211), and 42.9% versus 72.1% in the high-risk group (n = 73). A significant difference was noted in the moderate-risk (P = 0.044) and high-risk (P = 0.015) groups, but not in the low-risk group (P = 0.56).Conclusions. Positive peritoneal cytology is not a negative prognostic indicator itself, but it potentiates other prognostic indicators for endometrial cancer. Our findings also suggest that patients with positive peritoneal cytology in the absence of other adverse prognostic factors do not need upstaging.

Pretreatment assessment of prognostic indicators in endometrial cancer

Objective: The object of this study was to assess the association of histologic, cytokinetic, and molecular variables in preoperative endometrial samples with extrauterine disease, recurrence, and survival among patients with endometrial cancer. Study Design: In a case-cohort study of 125 women, ploidy, S-phase fraction, proliferative index, deoxyribonucleic acid index, proliferating cell nuclear antigen, MIB-1 proliferation marker, p53 tumor suppressor gene, and cytoplasmic HER-2/neu oncogene and bcl-2 expressions were quantitated. Results: A model with only one independent term predicted progression-free survival; that variable was p53 (P <.0001; relative risk, 5.60). A model with two independent terms predicted disease-related survival; these variables were p53 (P =.0002; relative risk, 7.39) and MIB-1 (P =.03; relative risk, 3.27). Among patients with tumors with both p53 and MIB-1 expression exceeding 33%, a total of 32% had died of disease by 2 years. A model for predicting extrauterine disease selected two independent variables: p53 (odds ratio, 3.20; P =.01) and ploidy (odds ratio, 2.16; P =.04). An advanced surgical stage was encountered in 26% to 35% of cases in which either the p53 expression exceeded 33% or the deoxyribonucleic acid content was nondiploid and in 53% of cases in which both variables were unfavorable. Conclusions: Preoperative evaluation of quantifiable cytokinetic and molecular variables can assist in identifying tumor types that are predisposed toward a more aggressive clinical course. (Am J Obstet Gynecol 2000;182:1535-44.)

Nuclear size, shape and summed optical density in endometrial cancer

Endometrial carcinoma is the most common gynecologic malignancy in developed countries affecting an estimated 140 000 women worldwide. Image analysis involves the integration of an optical microscope with a computer to describe cellular and nuclear features which may not otherwise be quantifiable. The authors, using image analysis, prospectively investigated three optical nuclear parameters to determine their relevance as prognostic indicators in endometrial cancer. Seventy-four consecutive patients with endometrial cancer, and who were being surgically treated, were evaluated for their DNA index (DI), time to recurrence, peritoneal cytology, depth of invasion, lymphovascular space invasion, FIGO stage, grade, histology, as well as nuclear size (NUSZ), shape (NUSH), and summed optical density (NUSD). DNA index, nuclear size, shape and density were quantified using image analysis. Fifteen patients had a recurrence of disease and 12 patients died from disease during the observation period of the study. Median follow-up was 31 months with a range from 1–44 months. Fifty patients had stage I cancers, five had stage II, 16 had stage III, and three had stage IV. Nuclear summed optical density correlated well with traditional prognostic indicators: depth of myometrial invasion (P = 0.003), histologic grade (P = 0.01), DNA index (P<0.001) and FIGO stage (P = 0.004). Nuclear size also correlated well with traditional prognostic indicators: depth of myometrial invasion (P = 0.002), histologic grade (P<0.001), progesterone receptor level (P = 0.005), DNA index (P<0.001), and FIGO stage (P = 0.001). Nuclear shape showed significant correlation only with FIGO stage (P = 0.002). The mean NUSD in patients with a recurrence of disease was 151.53 while the mean NUSD in patients without recurrence was 103.48 (P = 0.002). The mean NUSZ in patients with a recurrence of disease was 156.62 μm2 (P = 0.043). Multivariate analysis showed both NUSZ (P<0.0001) and NUSD (P<0.0001) to be independent prognostic variables. Image analysis is able to quantify cellular and nuclear parameters not otherwise quantifiable. Nuclear summed optical density and NUSZ correlated well with traditional prognostic indicators and were demonstrated to be significantly different in patients with recurrence of disease vs patients without recurrence.

Markov Texture Parameters as Prognostic Indicators in Endometrial Cancer

Background: Texture is a descriptive property of a surface distinct from color and shape. Image analysis allows gray-scale images to have their optical texture measured and analyzed. The authors, utilizing image analysis, prospectively studied Markov texture parameters to determine their relevance as prognostic indicators of disease recurrence in endometrial cancer. Methods: Seventy-four consecutive patients, surgically treated, with endometrial cancer, were evaluated for their DNA index (DI), time to recurrence, peritoneal cytology, depth of invasion, lymphovascular space invasion, FIGO stage, grade, histology, as well as 21 Markov parameters. DI and the Markov parameters were quantified using image analysis. Results: Median follow-up for the study population was 31 months with a range from 1 to 44 months. Fifteen patients had recurrence of their cancer and 12 patients died from disease during the observation period of the study. Eleven Markov parameters showed significant correlation with increasing FIGO stage (P< 0.05), while 14 Markov parameters showed significant correlation with survival (P< 0.05). Three Markov parameters, difference entropy (P= 0.025), information measure B (P= 0.01), and diagonal moment (P= 0.046), were demonstrated to be independent prognostic indicators along with the more traditional prognostic indicators, stage (P= 0.006), grade (P= 0.029), and depth of myometrial invasion (P= 0.03). Conclusion: Image analysis is able to quantify optical texture. Utilizing bivariate correlations and multivariate analysis, three of these parameters were demonstrated to be independent prognostic indicators in endometrial cancer, specifically difference entropy, information measure B, and diagonal moment.

Flow cytometric studies of ploidy and proliferative indices in the Yorkshire trial of adjuvant progestogen treatment of endometrial cancer

To estimate whether flow cytometric indices provide independent measures of prognosis or predict response to prophylactic progestogens in endometrial cancer. Endometrial tumour specimens were retrieved and analysed by flow cytometry from 257 women who had been randomly allocated in a previous trial to receive prophylactic progestogen in addition to conventional therapy for endometrial carcinoma. Fourteen district and two teaching hospitals in West Yorkshire. Women developing primary endometrial cancer between 1975 and 1983. Tumour ploidy status and proliferative indices and the relation of these to tumour stage and grade, to prognosis and to response to progestogens. Ploidy status and proliferative indices were related to tumour stage, grade and patient survival but were not independent predictors of survival. They did not predict patients who would respond to progestogens although there was a nonsignificant trend towards patients with diploid tumours surviving longer after progestogen treatment. Flow cytometry adds little to established prognostic indicators for endometrial cancer.

Oestrogen and progestin receptors as prognostic indicators in endometrial cancer. A review of the literature.

The history of research on oestrogen and progestin receptors in endometrial cancer goes back about 20 years. Summarized data from several clinical studies demonstrate that cytosol oestrogen (ERC) and progestin receptors (PRC) are clinically useful indicators of prognosis. Absence of receptor or its low concentration is indicative of an increased risk of recurrent malignancy. In this respect PRC tends to be more sensitive than ERC. In some studies PRC assay appeared to be more strongly correlated to prognosis than any of the conventional clinico-pathological parameters. In addition, the information obtained by ERC and/or PRC assay is independent of and additional to the classical prognostic indicators. The value of ERC and PRC assay in predicting the sensitivity of endometrial cancer to progestin therapy is of clinical interest. The accumulated data for many clinical trials show that in detecting the non-responders to progestin therapy negative results of ERC and PRC give similar information with an accuracy of about 90%. In identifying responders to progestin therapy, a positive PRC result appeared to give more precise information than a positive ERC, the accuracy being about 75% for PRC. The use of the combination of ERC and PRC determination as a prognostic indicator or predictor of sensitivity to progestin therapy does not significantly increase the information available by PRC measurement alone. Hence, whatever used--a biochemical ligand binding technique or immunohistochemical staining--PRC determination alone seems recommendable for clinical purposes.