Factors In Endometrial Cancer Research Articles

Prognostic factors in endometrial cancer

Prognostic factors in endometrial cancer

Prognostic factors in endometrial cancer

Introduction: Endometrial cancer (EC) is the most common malignancy of the female genital tract. It is now the fourth most common gynecological cancer among women and the sixth worldwide cancer in Western countries. It is the most curable of the 10 most common cancers in women and the most frequent and curable of the gynecologic cancers. The incidence is increasing when life expectancy rise. This study was carried out to evaluate the prognostic factors of Endometrial Cancer. Methods: Clinico-pathological characteristics and follow-up cases of endometrial cancer were analysed retrospectively between January 2000 to December 2007 with its prognostic factors influence were statistically analysed. Results: During the study period total 180 patients were taken. Univariate model revealed that the menopausal status, the FIGO stage, grade, histological type, myometrial invasion, ER, PR, peritoneal cytology, lymph node metastases, adjuvant therapy, and the method of operation were related with the prognosis significantly. The multivariate analysis Cox proportion hazards regression model showed that the ER (P=0.004), PR (P=0.000), myometrial invasion (P=0.006) and lymph node metastases (P=0.049) were related with the prognosis significantly. Conclusion: The clinico-pathological character of endometrial cancer is responsible for patient’s better survival. If the patients had early detection and treated in proper modalities, this might improve the good prognosis. DOI: http://dx.doi.org/10.2126/joim.v35i1.8891 Journal of Institute of Medicine, April, 2013; 35:9-17

The role of cytology and other prognostic factors in endometrial cancer

The clinical and prognostic value of positive cytology in women with endometrial cancer remains uncertain. The aim of our retrospective observational study was to determine whether in women with disease confined to the uterus, positive peritoneal cytology adversely affects disease-free (DFS) or overall survival (OS); to assess whether positive or negative cytology affects survival in women irrespective of stage and to assess whether the use of hysteroscopy or Pipelle for diagnosis affected cytology positivity rates. We have shown that median DFS and OS were almost identical for tumours confined to the uterus with and without positive peritoneal cytology. Women with tumours extending to the serosa or adnexa had a non-statistically significant shorter survival in comparison with women with stage I disease and negative cytology. Out of 59 women that had their cancer diagnosis based on a Pipelle biopsy of the endometrium, five had positive peritoneal washings. A total of 150 women had pre-treatment hysteroscopy; seven of these had positive peritoneal washings. There was no significant difference in the rates of positive cytology between these groups (4.6% vs 8.4%). In our cohort of un-staged women, positive peritoneal cytology did not adversely affect prognosis when disease was confined to the uterus.

Evaluation of Expression of the PTEN Gene, Oestrogen and Progesterone Receptors as Diagnostic and Predictive Factors in Endometrial Cancer

Endometrial cancer belongs to the commonest malignancy in females after breast cancer, malignant neoplasm of female genitals in Europe and North America but there is still not significant improvement as far as the curability of this neoplasm is concerned, especially its advanced forms. That is why there is need to define new factors that could be not only diagnostic but also predictve factors. In present study we analyzed the mRNA PTEN expression by quantitative real-time polymerase chain reaction (Q-PCR) in 123 women of endometrial carcinoma and 14 women of control group. Moreover we assessed oestrogen (ER) and progesterone receptors (PgR) in all cases. We defined the correlation between expression of PTEN gene and receptors and between PTEN expression and maturity grade of cancer. Neoplasm advancement grade G1 was diagnosed in 82.11 % of patients (n = 101), G2 in 9.76 % of patients (n = 12) and G3 in 8.13 % of patients (n = 10). Presence of ER and PgR and decreased expression of PTEN gene was found in majority of patients with endometrial cancer (79.12 % and 59.34 % respectively) and the most numerous group was with weak expression of ER and strong expression of PgR. There was no statistically significant difference in gene expression depending on receptors expression nor maturity grade of cancer (p > 0.05). Evaluation of expression of PTEN gene may turn out to be a very useful tool aimed at qualifying patients for different therapies of endometrial cancer and at searching of new diagnostic and therapeutic methods of this cancer independently on its receptor status nor maturity grade of cancer.

High-grade endometrial cancer: Revisiting tumor size and the lower uterine segment.

5589 Background: Tumor size is an independent poor prognostic factor in endometrial cancer, while tumor location has shown mixed results, with few studies addressing high-grade disease. We aim to determine if tumor size (TS) or lower uterine segment involvement (LUS) is associated with nodal disease and recurrence in high-grade endometrial cancer. Methods: In an IRB-approved, multi-institutional cohort study of patients with clinically early-stage, high-grade endometrial cancer (grade 3 and all non-endometrioid histologies), records were reviewed for demographic, pathologic, and treatment data. Recurrence as a function of tumor size and location were analyzed using logistic regression and exact tests for significance. Hazard ratios were calculated. Results: 208 patients with high-grade histology were identified from Jan 2005 to Jan 2012 with 188 patients having tumor location identified and 183 having tumor size reported. Both pelvic and para-aortic lymphadenectomy were completed in 100% of patients. There were 75 endometrioid (36.1%), 35 papillary serous (16.8%), 12 clear cell (5.8%), 26 carcinosarcoma (12.5%), and 60 (28.8%) with undifferentiated or mixed histology. Median follow up time was 17.2 months (0.2 – 67.6 mo) with 55 recurrences. LUS tumors were more likely to have pelvic and para-aortic nodal disease (OR 3.83, 95%CI 1.70 – 8.60, OR 5.13, 95% CI 1.96 – 13.45) and increased recurrence rates (HR 2.21, 95% CI 1.16-4.20) on univariate analysis. Tumors size ≥2cm was associated with pelvic nodal disease (27.4% vs. 0%, p = 0.01; OR 10.00, p = 0.01). TS was not independently associated with recurrence and patterns of failure did not significantly differ with LUS involvement. Conclusions: In patients with clinically early stage, high-grade endometrial cancers, TS and LUS tumor location are significantly associated with lymph node metastasis and advanced stage disease at the time of comprehensive surgical staging. Tumor location in particular is strongly associated with distant nodal disease and is a poor prognostic indicator for recurrence. Studies evaluating the role of adjuvant therapy based on tumor size and tumor location would be helpful in improving patient related outcomes.

L1-CAM as a predictor of survival in endometrial cancer: An analysis of The Cancer Genome Atlas (TCGA).

5599 Background: Despite a good survival rate for early-stage endometrial cancers (ECs), the prognosis for advanced-stage ECs remains poor, with no biomarkers and few therapeutic options currently in existence. L1-cell adhesion molecule (L1-CAM), a glycoprotein which functions in adhesion and migration of tumor cells, has been associated with a poor prognosis in Type I endometrial cancer (ASCO 2011 Abstract #5091). We evaluated the role of L1-CAM among both Type I and II ECs in TCGA. Methods: Partek Genomics Suit was used to define differentially expressed genes with p-values for clinical associations (ANOVA with linear contrast for discrete variables and linear regression for continuous variables). Differences in survival between “high” and “low” expression groups (defined by median expression) were compared using Cox regression analysis, with p-values calculated via log-rank test, using the ‘survival’ package in R. Results: Of 451 downloadable tumor samples, 335 tumors with both clinical and gene expression data were analyzed. Median age was 63 yrs. (range 31-90 yrs.). Stage I, II, III, and IV comprised 65%, 7%, 23%, and 5%, respectively. 82% were endometrioid; 16% (n = 52) serous. Grade 1, 2, and 3 comprised 24%, 27%, and 49%, respectively. Median follow-up was 19.5 months. High L1-CAM expression was found in older (p = 0.0005), suboptimally debulked (p=0.002), and African-American patients (p = 0.0003), and those with high grade (p = 0.008), serous histology (p <0.00001), higher stage (p = 0.0004), positive peritoneal cytology (p = 0.007), deep myometrial invasion (p = 0.02), and positive pelvic (p = 0.003) and para-aortic lymph nodes (p = 0.002). High L1-CAM expression was associated with poor survival with a median overall survival of 17.2 months compared to 21.3 months for low L1-expressing endometrial tumors (HR= 3.1, CI=1.3 -7.3, p = 0.007). Conclusions: L1-CAM expression is associated with poorer survival and high-risk clinicopathologic factors in endometrial cancer. Its prevalence in Type II ECs, such as high-grade, serous ECs, makes it a particularly attractive target for both novel biomarker discovery and therapeutic targeting.

The impact of diabetes and obesity on endometrial cancer outcomes.

5523 Background: Diabetes (DM) is a known risk factor for endometrial cancer (EC), yet its effect on cancer outcomes remains unclear. We sought to investigate of the relationship between DM, obesity, and anti-diabetic medication on EC recurrence and survival. Methods: An IRB approved multi-institution retrospective study included all EC patients diagnosed with carcinosarcoma as well as endometrioid, serous, and clear cell cancers between January 2005 to December 2010. Demographics, comorbidities, and medications were captured at the time of cancer diagnosis. Cohorts for comparison included women with and without DM; and diabetics treated with metformin-only (METFO) were compared to those not treated with METFO. Cox regression models were used to evaluate the effect of selected covariates on PFS and OS. Results: Of 1495 EC patients, 364 (24%) had DM. Diabetics were more likely to be African American (30 v 16%, p<0.0001) and have higher BMIs (median 37.0 v 31.2, p < 0.001). After adjusting for age, race, stage, and BMI, women with DM had a worse OS (HR 1.40, 95CI 1.03-1.79), but similar recurrence risk (HR 1.16, 95CI 0.91-1.48) to non-diabetics. In a subset analysis of women with endometrioid EC (n = 1144), those with DM were 1.6 times more likely to recur (95CI 1.01-1.89, p = 0.04) and 2.4 times more likely to die (95CI 1.6-3.46, p < 0.0001). METFO use was associated with a decreased risk of recurrence (PFS HR 0.54, 95CI 0.3-0.96, p = 0.04), and death (OS HR 0.43, 95CI 0.22-0.83, p = 0.01) compared to no METFO use. METFO users had a similar clinical outcome compared to non-diabetics (PFS HR 1.05, p = 0.82; OS HR 1.3, p = 0.46). Obese women with DM who were treated with non-METFO regimens had a 1.8-fold increased risk of recurrence (95CI 0.94-3.7, p = 0.07) and 2.7-fold increased risk of death (95CI 1.2-5.9, p = 0.01). No survival differences were seen in women with serous, clear cell, or carcinosarcoma. Conclusions: Our data demonstrates worse clinical outcomes for EC patients with DM and improved outcomes for METFO users, suggesting a link between tumor pathogenesis and insulin growth factor and mTOR pathways. Future investigation is required to elucidate the complex relationship between diabetes, anti-hyperglycemic agents, and cancer outcomes.

Relationship between the expression levels of PAPP-A metalloproteinase and growth and transcriptional factors in endometrial cancer

We have examined for the first time the relationship between the expression of PAPP-A metalloproteinase and insulin-like growth factors (IGF-I, IGF-II, VEGF) and transcription factors (NF-kappaB, HIF-1) playing an important role in pathogenesis of cancer. We also demonstrated a positive association between the level of PAPP-A metalloproteinase and the level of growth (VEGF and IGF-I) and transcription factors (NF-kappaB p50, NF-kappaB p65, HIF-1alpha). The current findings suggest an important role of PAPP-A in regulation of bioavailability of IGF-I, VEGF, activated forms of NF-kappaB, and alpha-subunits of HIF-1 in endometrial tumors.

Prognostic factors in endometrial cancer

Prognostic factors in endometrial cancer

Abstract 151: Obesity is independently associated with mTORC1 pathway activation in the progression of endometrial cancer.

Abstract Background: Obesity is a major risk factor for endometrial cancer (EC) yet, with the exception of estrogen, the mechanisms underlying this association remain unclear. The mammalian target of rapamycin complex 1 (mTORC1) cascade links energy balance to cell proliferation via the PI3K/Akt pathway. Phosphorylation of Akt by hormone and growth factor signaling activates mTORC1 and results in the downstream phosphorylation of 4EBP1. Activated 4EBP1 positively regulates cap-dependent translation and cell growth, and correlates with EC progression. Thus, we explored the associations between obesity and pAkt and p4EBP1 expression, and cell proliferation rates (Ki67) in benign and malignant endometrial tissues. Methods: Medical records were reviewed to identify women who underwent endometrial biopsy at UAB Hospital from 2008-2010. Women who had recurrent EC or diagnoses of any other cancer were excluded. Data on diagnosis, height, weight, race, age, menopausal status, number of children, medications, and comorbid conditions were extracted from medical records. Height and weight were used to calculate body mass index (BMI: kg/m2). A gynecologic pathologist reviewed H&E slides for concordance with the pathology report, and additional sections were obtained from formalin-fixed paraffin-embedded tissue blocks. Immunohistochemistry was used to assess p4EBP1, pAkt, and Ki67. The pathologist employed a semiquantitative scoring system based on percent positive and staining intensity for p4EBP1 and pAkt, and scored on percent positive for Ki67. Wilcoxon rank-sum tests were used to compare marker activity between women with and without EC in the overall and BMI-stratified sample. Results: Immunohistochemical data were available for 18 benign and 25 type 1 endometrioid EC cases, of which 29 were obese (BMI > 29.9) and 14 were non-obese (BMI ≤ 29.9); the overall mean BMI was 35.5 (SD=11.6). Mean age was 56.7 (12.2). Women with vs. without EC had significantly elevated median [interquartile range] expression of cytoplasmic p4EBP1 (95 [30-180] vs. 0 [0-20], p=0.001), nuclear p4EBP1 (170 [95-195] vs. 70 [20-100], p=0.003), and Ki67 (50 [40-80] vs. 10 [5-20], p<0.0001). EC was not associated with pAKT activity. While obese women with vs. without EC had significantly higher expression of cytoplasmic p4EBP1 (100 [80-180] vs. 0 [0-10], p=0.002) and nuclear p4EBP1 (180 [100-200] vs. 65 [20-100], p=0.002), neither cytoplasmic nor nuclear p4EBP1 activity differed by EC status among non-obese women. No associations between obesity and Ki67 or pAKT were detected. Conclusions: Results from this exploratory study suggest that p4EBP1 expression is elevated in obese women with EC. These preliminary findings suggest that obesity may play a role in EC-related activation of the mTORC1 pathway and 4EBP1, a biomarker for EC outcomes. Citation Format: Emily Falk Libby, Maria Azrad, Lea Novak, Wendy Demark-Wahnefried. Obesity is independently associated with mTORC1 pathway activation in the progression of endometrial cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 151. doi:10.1158/1538-7445.AM2013-151

Abstract 2285: Risk factors for endometrial cancer in black and white women: A pooled analysis from the Epidemiology of Endometrial Cancer Consortium (E2C2).

Abstract Introduction: More than 47,000 women will be diagnosed with endometrial cancer in 2012, making it the most common gynecologic cancer among women in the United States. Data from the SEER registry from 1975-2009 report the incidence rate of endometrial cancer is lower among black women than white women (19.2 and 27.5 cases per 100,000 women, respectively). Tumor histology also varies by racial group, with a larger proportion of black women diagnosed with non-endometrioid tumors compared to their white counterparts. It is possible that risk factors for endometrial cancer may differ between black and white women; the small number of black women in individual studies has precluded these analyses. The aim of this study was to investigate risk factors for endometrial cancer in blacks using a pooled analysis. For comparison, we pooled data on risk factors among non-Hispanic white women in the same studies. Methods: We have data from eleven studies that included >10 black cases and >10 black controls (7 cohort studies and 4 case-control studies). The following information was collected from each study: age at diagnosis/study entry, education, body mass index (BMI), smoking status, reproductive variables, hormone use, and self-reported diabetes and hypertension. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals for each risk factor in blacks and whites separately. Estimates for endometrioid tumors will also be presented. Results: Data were pooled for 2,011 black women (516 cases and 1,495 controls) and 19,297 white women (5,693 cases and 13,604 controls). In univariate analyses, the following variables were associated with endometrial cancer in both black and white women: BMI, smoking, oral contraceptive use for 10 years or more, and diabetes. In models adjusted for these variables, along with age and study site, obesity (BMI ≥ 30) was associated with an approximate 3-fold increase in risk for both black and white women (OR=2.80, 95% CI: 2.00, 3.92 and OR=3.26, 95% CI: 2.96, 3.59, respectively). Diabetes was also associated with a 30-40% increase in risk among both groups. Cigarette smoking was associated with reduced risk of endometrial cancer among both blacks and whites (OR=0.66, 95%CI: 0.47, 0.94 and OR=0.62, 95% CI: 0.54, 0.71, respectively). Increasing parity was more strongly associated with decreased risk in whites (p-trend <0.001) than blacks (p-trend = 0.09). Similarly, age at first birth was also more protective in whites (p-trend<0.001) than blacks (p-trend=0.76). Conclusions: Overall, risk factors for endometrial cancer are similar in black and white women, with the exception of some of the reproductive factors, which do not appear to afford protection in blacks to the same extent as in whites. Citation Format: Michele L. Cote, Tala Alhajj, Julie J. Ruterbusch, Louise A. Brinton, William J. Blot, Chu Chen, Brian E. Henderson, Pamela L. Horn-Ross, Laurence N. Kolonel, Timothy R. Rebbeck, Veronica W. Setiawan, Lisa B. Signorello, Michael S. Simon, Noel S. Weiss, Nico Wentzensen, Hannah P. Yang, Sara H. Olson. Risk factors for endometrial cancer in black and white women: A pooled analysis from the Epidemiology of Endometrial Cancer Consortium (E2C2). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2285. doi:10.1158/1538-7445.AM2013-2285

Abdominal adiposity through adipocyte secretion products, a risk factor for endometrial cancer

Background and aim: The adipose cell has been considered an inert cell from a secretory point of view. Studies over the past years have confirmed the capacity of the adipocyte to synthesize many substances including: adiponectin, leptin, which integrate multiple metabolic and endocrine signals. In the context of endometrial cancer, abdominal obesity as a risk factor is associated with a chronic inflammatory process, confirmed by the increase of inflammatory markers. The study aimed to identify a correlation between abdominal obesity, plasma adipokine levels and endometrial cancer.Material and method: Two groups of patients were included in the study: group I – 44 patients diagnosed with endometrial cancer, group II – 44 patients without gynecological pathology or inflammatory disorders. After the performance of clinical examination and anthropometric measurements, abdominal fat was determined by dual X-ray absorptiometry and plasma adiponectin and leptin levels were measured.Results: A significantly higher abdominal fat and leptin value was found in the group of patients in with endometrial cancer (p < 0.0001), while the plasma adiponectin level was significantly lower, compared to the control group (p < 0.0001). Abdominal fat was in a negative linear correlation with the plasma adiponectin level and in a positive linear correlation with the plasma leptin level.Conclusions: The measurement of adiponectin and leptin levels associated with the determination of abdominal adipose tissue can be a useful predictor factor for endometrial cancer.

Combination analysis of Bub1 and Mad2 expression in endometrial cancer: act as a prognostic factor in endometrial cancer

This study aimed to evaluate the diagnostic value of Bub1 and Mad2 together in endometrial cancer. Sixty-three patients with endometrial cancer, including EECs and NEECs, were examined statistically. Bub1 and Mad2 in patient tissues were detected by indirect streptavidin-biotin-peroxidase complex method. 39 cases (61.9 %) were in clinical stage I, 17 cases (27 %) in stage II, 5 (7.9 %) in stage III and 2 cases (3.2 %) in stage IV. Bub1 positive and Mad2 positive rate were identified in 18 and 54 patients. The lower positive of Bub1 and higher positive rate of Mad2 were related to clinical stage and histological grade of endometrial cancer (P = 0.009, 0.002, respectively), especially in NEECs. The expression of Bub1 was negatively correlated with Mad2 and Mtp53 (both P < 0.05). The expression of Mad2 with Mtp53 was positively correlated (P < 0.05). Statistically significant difference between Bub1/Mad2 expression and survival was discovered in endometrial cancer. Specificity and sensitivity of combination between Bub1 negative and Mad2 positive cases were higher than those alone in NEEC subtype. Bub1 and Mad2 are associated with histological differentiation, clinical stage and decreased postoperative survival in endometrial cancer. The combination analysis of Bub1 and Mad2 might be the valuable prognostic, even diagnostic clinicopathologic factor which can be applicable in routine examination.

Abstract 14: Body mass index and type 2 diabetes genetic risk scores and endometrial cancer risk among women of European ancestry.

Abstract Obesity and type 2 diabetes mellitus (T2D) are independent risk factors for endometrial cancer. While they are mainly considered a consequence of modifiable lifestyle choices, increasingly, genetic determinants are discovered. Genome-wide association studies (GWAS) have identified common variants that predispose individuals to a higher body mass index (BMI) or T2D. One study found that summing the number of BMI-increasing alleles from 26 unique loci into a genetic risk score (GRS) was associated with increased endometrial cancer risk among Chinese women. Since the majority of BMI and T2D variants were identified in populations of European descent, we explored whether the respective GRSs are associated with endometrial cancer risk among women of European ancestry. We used data from an ongoing GWAS conducted by the Epidemiology of Endometrial Cancer Consortium. Samples were genotyped on the Illumina HumanOmniExpress, HumanOmni2.5, or Human660W chip. Over 2.5 million markers were imputed separately for each study using MACH software (r2 &amp;gt;0.80) and NCBI build 36 of Phase II HapMap CEU (release 22) as the reference panel. We selected all 32 independent variants validated and/or identified at P&amp;lt;5x10^-8 from a recent genome-wide meta-analysis for the BMI GRS. Similarly, we selected 36 independent polymorphisms near 35 loci that replicated in GWAS of T2D. Exported counts of each risk allele were used to calculate the BMI and T2D GRSs. Data were available for 2,656 Type I endometrial cancer cases and 2,730 control participants of European ancestry. Unconditional logistic regression examined the association of individual variants and GRSs with endometrial cancer risk or diabetes. Linear regression assessed genetic associations with BMI. All analyses were adjusted for age and study. BMI, diabetes, menopausal hormone therapy (HT) use were also considered. Binomial tests assessed whether the number of risk alleles associated with elevated endometrial cancer risk was more than expected by chance. Likelihood ratio tests assessed heterogeneity by age, BMI, and HT use strata. Women with endometrial cancer were slightly older and more likely to have used HT. Cases also had a higher mean BMI and were more likely to have a personal history of diabetes. Among controls, the BMI GRS was strongly associated with BMI (beta=0.23; P=5.50x10^-16). Twenty-four of 32 obesity risk alleles displayed estimates consistent with increased endometrial cancer risk (binomial test, P=0.001). The BMI GRS was significantly associated with endometrial cancer risk. Per risk allele, a woman had a 2% increased risk of endometrial cancer (95% CI=1%-4%; P=0.004). After adjusting for BMI, the BMI GRS was no longer associated with endometrial cancer risk (per-allele OR=1.00; 95% CI=0.98-1.02; P=0.97). Heterogeneity was not noted by age, BMI, or HT use (P&amp;gt;=0.25). Of 36 T2D risk alleles, the number associated with elevated endometrial cancer risk (N=12) was not more than expected by chance (binomial test, P=0.97). The T2D GRS was not associated with a personal history of diabetes among controls (P=0.25) or with endometrial cancer risk (P=0.06). Heterogeneity was not observed by age, BMI, or HT use (P&amp;gt;=0.10). In summary, possessing a greater number of obesity risk alleles increases endometrial cancer risk among women of European ancestry. However, this risk can be eliminated by maintaining a healthy body weight. We did not find an association with the T2D GRS, with 65% power to detect a per-allele OR of 1.02. Citation Format: Jennifer Prescott, Veronica W. Setiawan, Nicolas Wentzensen, Fredrick Schumacher, Herbert Yu, Ryan Delahanty, Stephen Chanock, Chu Chen, Monserrat Garcia-Closas, Christopher A. Haiman, Patricia Hartge, Pamela Horn-Ross, Loic Le Marchand, Jolanta Lissowska, Lingeng Lu, Harvey A. Risch, Xiao-Ou Shu, Giske Ursin, Noel S. Weiss, Hanna Yang, Peter Kraft, Immaculata De Vivo. Body mass index and type 2 diabetes genetic risk scores and endometrial cancer risk among women of European ancestry. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 14.

M304 ANDROID FAT EVALUATED TROUGH DUAL X-RAY ABSIORPTIOMETRY, CORRELATED WITH SYSTEMIC INFLAMMATORY STATUS, A RISK FACTOR FOR ENDOMETRIAL CANCER

International Journal of Gynecology & ObstetricsVolume 119, Issue S3 p. S629-S629 Poster presentations M304 ANDROID FAT EVALUATED TROUGH DUAL X-RAY ABSIORPTIOMETRY, CORRELATED WITH SYSTEMIC INFLAMMATORY STATUS, A RISK FACTOR FOR ENDOMETRIAL CANCER R. Ciortea, R. CiorteaSearch for more papers by this authorN. Costin, N. CostinSearch for more papers by this authorO. Mihaela, O. MihaelaSearch for more papers by this authorP. Ciprian, P. CiprianSearch for more papers by this authorA. Malutan, A. MalutanSearch for more papers by this authorM. Radu, M. RaduSearch for more papers by this authorD. Haragas, D. HaragasSearch for more papers by this authorO. Buta, O. ButaSearch for more papers by this authorD. Mihu, D. MihuSearch for more papers by this author R. Ciortea, R. CiorteaSearch for more papers by this authorN. Costin, N. CostinSearch for more papers by this authorO. Mihaela, O. MihaelaSearch for more papers by this authorP. Ciprian, P. CiprianSearch for more papers by this authorA. Malutan, A. MalutanSearch for more papers by this authorM. Radu, M. RaduSearch for more papers by this authorD. Haragas, D. HaragasSearch for more papers by this authorO. Buta, O. ButaSearch for more papers by this authorD. Mihu, D. MihuSearch for more papers by this author First published: 22 October 2012 https://doi.org/10.1016/S0020-7292(12)61495-7AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume119, IssueS3Abstracts of XX FIGO World Congress of Gynecology and ObstetricsOctober 2012Pages S629-S629 RelatedInformation

Life-style and metformin for the prevention of endometrial pathology in postmenopausal women

In western women, the endometrium is frequently exposed, even after menopause, to the endogenous hormonal stimulation. Such a stimulation increases the risk of pathologic conditions such as endometrial hyperplasia and type I (endometrioid) endometrial adenocarcinoma. Metabolic syndrome, obesity, insulin resistance and type II diabetes promote the endometrial stimulation, and are recognized risk factors for endometrial cancer. Furthermore, chronic hyperinsulinemia linked both to obesity and metabolic syndrome influences endometrial proliferation through direct and indirect actions. Intentional weight loss, calorie restriction and physical activity are associated with a reduced risk of the endometrial pathology. Biological mechanisms include reduction in insulin and sex steroid hormone levels. In addition to life-style modifications, the antidiabetic metformin may be proposed as preventive agent. Metformin reduces the metabolic syndrome, lowers insulin and testosterone levels in postmenopausal women, and it is a potent inhibitor of endometrial cancer cell proliferation.

Etiology and Fertility Preservation Treatment for Young Women with Endometrial Cancer

Abstract Objective: The purpose of this review is to evaluate the risk factors for endometrial cancer in young women as well as fertility preservation options. Design: A literature search using the key words fertility preservation, endometrial cancer, uterine cancer, and risk factors was conducted in MEDLINE,® EMBASE, and the Cochrane Database of Systematic Reviews. Results: Etiologic factors for development of endometrial cancer were discussed. All available conservative options to avoid hysterectomy were also discussed. Treatment outcome for young women with endometrial cancer treated by systemic progestins was summarized. Conclusions: In women with early stage well-differentiated endometrial cancer, conservative treatment with progestins should be considered. It is important to note that this is a temporary treatment that has to be followed by a definitive treatment after completion of the patient's family. Proper counseling and close follow-up are mandatory. Because of the rarity of the disease in you...

Abstract 4475: Association of endometrial cancer risk factors and DNA methylation in benign endometrial tissue

Abstract Background: Increased risk for endometrial cancer is related to factors such as use of unopposed estrogen and obesity, and decreased risk is associated with oral contraceptive use and smoking. However, little is known about the molecular mechanisms by which these factors influence cancer risk. DNA methylation of promoter regions in tumor suppressor genes has been linked to endometrial cancer, suggesting DNA methylation may mediate the effects of risk factors on normal endometrium, leading to increased risk for cancer. Accordingly, we explored relationships between risk factors for endometrial cancer and DNA methylation patterns assessed in normal endometrial tissue. Materials and Methods: Formalin fixed paraffin embedded endometrial tissues from 63 women aged 28-53 (median= 43) who underwent a hysterectomy for benign indications were studied. DNA isolated from 1.0-mm cores was bisulfite treated and methylation profiles were generated using Illumina's GoldenGate array which includes 1505 CpG sites representing over 800 genes. Unsupervised hierarchical clustering analysis was used to identify groups of patients with similar methylation patterns and class comparison analysis was employed to identify differentially methylated genes based on predefined categories, representing endometrial cancer risk factors. Results: Global changes in DNA methylation, as measured by total or average methylation levels or clustering analysis were not associated with age. However, methylation levels of MT1A (p=0.0002) and CDH13 (p=0.0009) were increased and methylation levels of PKD2 (p=0.0009) were decreased among older women. Increased methylation of HS3ST2 (p=0.00006), MLF1 (p=0.0001), PLAUR (p=0.0004), MLH3 (p=0.0007), ISL1 (p=0.0007), and RASSF1 (p=0.0009) was related to women with a lifetime menstrual span of more than 30 years compared to those who reported having menstruated for less than 15 years. One gene (MMP3) was more methylated in women who had an older age at menarche (14+ years old) compared to those who had a younger age at menarche (&amp;lt;12 years old, p=0.0008). Furthermore, unsupervised hierarchical clustering suggested that age at menarche (p=0.05) distinguished three groups of women who had distinct methylation patterns. Conclusions: Our results suggest that DNA methylation patterns at specific loci from normal tissue are related to attained age, age at menarche and the lifetime menstrual span of women. In conjunction with methylation profiling of endometrial cancer, these data may demonstrate the importance of DNA methylation as a mechanism in the pathogenesis of endometrial cancer and lead to potential biomarkers for early detection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4475. doi:1538-7445.AM2012-4475

Abstract 1029: The association of body mass index with risk of endometrial cancer subtypes: Pooled analysis in E2C2

Abstract Excess body weight is a known risk factor for endometrial cancer but whether it differentially affects histological subtypes of endometrial cancer is unclear. The two proposed main subtypes are the “estrogen-dependent Type I” and “non estrogen-dependent and clinically aggressive Type II”. Little is known about risk factors for Type II tumors mainly because most epidemiologic studies lack sufficient cases to study these rare tumors separately. Here we examined the association between recent adult body mass index (BMI) and endometrial tumor subtypes in a pooled analysis of 25 studies in the Epidemiology of Endometrial Cancer Consortium (E2C2). Individual-level data from 10 cohort studies and 15 case-control studies provided a total of 14,409 endometrial cancer cases and 35,950 controls for this analysis. Cohort studies were analyzed using a nested case-control design. The majority of women were white (86%) and postmenopausal (83%). Endometrial cancer cases were classified into two subtypes: Type I (endometrioid adenocarcinomas, adenocarcinoma tubular, papillary adenocarcinomas, mucinous adenocarcinomas, adenocarcinomas with squamous metaplasia, n=13,286) and Type II (serous, squamous cell, small cell, mixed cell, n=1,123). The associations of BMI with the risk of tumor subtypes were evaluated by calculating odds ratios (OR) and 95% confidence intervals (95% CI) using polytomous logistic regression models. Potential confounders included in the analysis were age, race, parity, age at menarche, oral contraceptive (OC) use, menopausal hormone (PMH) use, and smoking status. BMI was positively associated with both Type I and Type II tumors, but the association was stronger for Type I than for Type II tumors (P value for the difference in OR between Type I and Type II was &amp;lt;0.0001). The OR associated with each five kg/m2 increase in BMI (OR5) was 1.58 (95% CI: 1.55, 1.62) for Type I and 1.35 (95% CI: 1.28, 1.42) for Type II. In the analysis of individual histologic types, the OR5 was lowest for serous tumors (1.28), moderate for mixed cell and clear cell (1.33-1.37), and highest for endometrioid tumors (1.60) and various adenocarcinoma groups (1.54-1.58). The associations of BMI with both Type I and II tumors were greater among postmenopausal women who never used PMH [OR5 = 1.84 (95% CI: 1.78, 1.89) for Type I and 1.48 (95% CI: 1.38, 1.58) for Type II] than among estrogen-only users [OR5 = 1.20 (95% CI: 1.13, 1.28) for Type I and 1.05 (95% CI: 0.87, 1.26) for Type II] or among estrogen-progestin users [OR5 = 1.33 (95% CI: 1.25, 1.41) for Type I and 1.12 (95% CI: 0.95, 1.33) for Type II]. Other known endometrial cancer risk factors such as OC use, parity, and smoking did not appear to modify the association between BMI and tumor subtype. In this large pooled analysis, we observed that BMI is a risk factor for all types of endometrial cancer, although, the association is consistently stronger for Type I than for Type II tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1029. doi:1538-7445.AM2012-1029

Correlation Between Preoperative Serum CA 125 and Surgicopathologic Prognostic Factors in Endometrial Cancer

Objective: This prospective study was conducted to determine the correlation between preoperative serum CA 125 and the presence of surgicopathologic prognostic factors in endometrial cancer. It also aimed to determine the CA 125 value which best predicted the prognostic factors to which it was significantly correlated. Methods: Patients with endometrioid endometrial cancer eligible for primary surgery were included. CA 125 determination using a chemiluminescent enzyme immunoassay (CLEIA) was done before surgery. Patients underwent laparotomy, peritoneal fluid cytology, extrafascial/radical hysterectomy, bilateral salpingooophorectomy, bilateral pelvic lymph node dissection and para-aortic lymph node sampling. Specimens were examined for tumor differentiation, lymphovascular space invasion, myometrial invasion, cervical, adnexal and vaginal involvement, pelvic and para-aortic lymph node metastases and for the presence of tumor cells in the peritoneal fluid. Correlation between CA 125 and the prognostic factors was analyzed using Pearson r correlation test. A receiver operating characteristic curve (ROC) was constructed to determine the CA 125 cutoff value. Results: Ninety patients were included in the analysis. Preoperative serum CA 125 was significantly correlated with deep myometrial invasion (σ = 0.24, p = 0.02), adnexal metastasis (σ = 0.26, p = 0.01) and pelvic (σ = 0.31, p < 0.01) and para-aortic lymph node involvement (σ = 0.43, p < 0.01). It was also significantly correlated with the presence of extrauterine disease (σ = 0.26, p = 0.01). A value of 55 U/mL can predict extrauterine spread with sensitivity of 53.85%, specificity of 84.38% and accuracy of 75.56%. Using this cutoff, the odds of a positive test is 3.44 and the odd of a negative test is 0.54. Conclusion: Preoperative serum CA 125 has a statistically significant correlation with deep myometrial invasion, adnexal metastasis, pelvic and para-aortic lymph node involvement and extrauterine disease, at a cutoff value of 55 U/mL. CA 125 determination should be routinely performed as part of the preoperative work-up for patients with endometrioid endometrial cancer.