Histological Type Of Endometrial Cancer Research Articles

COMPARATIVE CONCLUSIONS OF DIAGNOSIS IN UTERINE BODY CANCER

Evaluation of the effectiveness and diagnostic accuracy of the Pipelle device in the early stages of endometrial sampling, precancerous diseases, including endometrial hyperplasia, atypical hyperplasia, endometrial polyps, and various histological types of endometrial cancer, compared to the traditional curette.

Association of high expression of CD44 in clinicopathological factors of endometrial cancer.

Clinical stages, histologic type, degree of cell differentiation, myometrial invasion, and lymph-vascular space invasion (LVSI) have been identified as clinicopathological factors that are predictive for endometrial cancer, however, further prognostic indicators are still required to account for the heterogeneity of this cancer. Adhesion molecule CD44, affects the invasion, metastasis, and prognosis of many forms of cancer. The purpose of this study is to examine the expression of CD44 in endometrial cancer and its correlation with established prognostic variables. A cross-sectional study was conducted on 64 samples of endometrial cancer from Wahidin Sudirohusodo Hospital and Hasanuddin University Hospital. Immunohistochemical analysis was used to detect CD44 expression using mouse anti-human CD44 monoclonal antibody. Differences in Histoscore were studied to determine the association between CD44 expression and clinicopathological factors of endometrial cancer. Of the overall sample, 46 samples were in the early stage, whereas 18 samples were in the advanced stage. High expression of CD44 was associated with advanced stage compare than early stage (P=0.010), poor differentiation compare than well-moderate differentiation (P=0.001), myometrial invasion ≥50% compare than myometrial invasion <50% (P=0.004), and positive LVSI compare than negative LVSI (P=0.043) in endometrial cancer, but not associated with histological type of endometrial cancer (P=0.178). High expression of CD44 may be considered as a poor prognostic marker and predictive marker for targeted therapy in endometrial cancer.

The histological type of endometrial cancer is not associated with menopause status at diagnosis.

The latest evidence suggests that type 2 endometrial cancer may not be completely oestrogen-independent, indicating that the status of hormonal change may not be associated with the traditional classification of endometrial cancer, including the histological subtypes. However, this has not been investigated. Menopause is commonly considered a state of hormonal change in women. In the present study, we investigated the association of menopause with the histological types of endometrial cancer. Data on the histological type, menopause status at diagnosis, age at diagnosis, parity, body mass index (BMI), and overall survival rate from 2122 cases were collected. The difference in risk in developing type 1 or type 2 endometrial cancer between premenopausal and postmenopausal patients was 5.457%. A statistical difference in the association of menopause with the histological types between the two groups was seen in endometrioid and serous carcinoma, with a risk difference of 5.6 or 3.8%. A statistical difference in the association of menopause with parity between the groups was only seen in endometrioid and adenosquamous carcinoma, with a risk difference of 7.1 or 3.7%. However, BMI was not associated with histological type and the overall survival rate was not associated with menopause (P=0.764). We reported a relatively small difference in the association of menopause with type 1 or type 2, or the histological types of endometrial cancer. The survival rate was not associated with menopause. Our study suggests that menopause status at diagnosis was not strongly associated with the histological subtypes of endometrial cancer.

Autophagy Machinery as a Promising Therapeutic Target in Endometrial Cancer.

Endometrial cancer is the fourth most frequent neoplasia for women worldwide, and over the past two decades it incidence has increased. The most common histological type of endometrial cancer is endometrioid adenocarcinoma, also known as type 1 endometrial cancer. Endometrioid endometrial cancer is associated with diverse epidemiological risk factors including estrogen use, obesity, diabetes, cigarette smoking, null parity, early menarche, and late menopause. Clinical effectiveness of chemotherapy is variable, indicating that novel molecular therapies against specific cellular processes associated to cell survival and resistance to therapy, such as autophagy, urged to ameliorate the rates of success in endometrial cancer treatment. Autophagy (also known as macroautophagy) is a specialized mechanism that maintains cell homeostasis which is activated in response to cellular stressors including nutrients deprivation, amino acids starvation, hypoxia, and metabolic stress to prolong cell survival via lysosomal degradation of cytoplasmic macromolecules and organelles. However, in human cancer cells, autophagy has a controversial function due to its dual role as self-protective or apoptotic. Conventional antitumor therapies including hormones, chemotherapy and ionizing radiation, may activate autophagy as a pro-survival tumor response contributing to treatment resistance. Intriguingly, if autophagy continues above reversibility of cell viability, autophagy can result in apoptosis of tumor cells. Here, we have reviewed the mechanisms of autophagy described in endometrial cancers, including the role of PI3K/AKT/mTOR, AMPK-mTOR, and p53 signaling pathways that trigger or inhibit the process and thus representing potential molecular targets in therapeutic clinical approaches. In addition, we discussed the recent findings indicating that autophagy can be modulated using repurposing drugs which may leads to faster experimentation and validation, as well as more easy access of the medications to patients. Finally, the promising role of dietary compounds and microRNAs in autophagy modulation is also discussed. In conclusion, although the research about autophagy is scarce but ongoing in endometrial cancer, the actual findings highlight the promising usefulness of novel molecules for directing targeted therapies.

Second primary uterine malignancies after radiation therapy for cervical cancer.

Radiation exposure has long been established as a risk factor for cancer development. The purpose of this study is to assess the risk of uterine malignancy in patients previously treated for cervical cancer with radiation therapy. A population-based cohort of 9092 patients diagnosed with cervical cancer who did not undergo surgery and received radiation therapy between 1973 and 2008 was identified from the Surveillance, Epidemiology and End Results Program database (SEER 9). Patients in this cohort who developed endometrial cancer after treatment of cervical cancer were identified. 55,140 patients with endometrial cancer were also identified. The distribution of the different histologic types of endometrial cancer was determined for each of these cohorts. 54 patients (0.6%) were diagnosed with an endometrial cancer more than 12months after diagnosis of cervical cancer. The average latency to endometrial cancer diagnosis was 160months, with a range of 14-374months. The average age of cervical cancer diagnosis was 52years and the average age at subsequent endometrial cancer diagnosis was 66years. Only 40% of the endometrial cancers diagnosed following treatment of cervical cancer were endometrioid. The majority were clear-cell adenocarcinomas (42%), 9% were carcinosarcomas and 5.5% were leiomyosarcomas. Of the 55,140 endometrial cancer patients in the database, a vast majority were endometrioid adenocarcinomas (91%), and only 2.3% clear-cell adenocarcinoma, 2.3% carcinosarcoma and 0.5% leiomyosarcoma. The difference in histologic type distribution between these two cohorts is highly significant (p < 0.01). A small proportion of women who receive radiation for cervical cancer go on to develop endometrial cancer. These are predominantly of the more aggressive histologic types when compared to primary endometrial cancers. The latency from cervical cancer diagnosis to endometrial cancer diagnosis is over a decade. In a patient who still has a uterus after receiving pelvic radiation, vaginal bleeding should be investigated.

Clinicopathologic and survival analysis of synchronous primary endometrial and ovarian cancer

Objective: To demonstrate the clinicopathological characteristics and determine the prognostic factors for women with synchronous primary endometrial and ovarian cancer (SEOC) . Methods: A retrospective analysis of 63 pathologically proven cases of SEOC diagnosed in Peking Union Medical College Hospital from January 2000 to May 2018 was carried out. Results: (1) Clinical features: mean age at diagnosis was (48.3±10.0) years, and the mean body mass index (BMI) was (23.4±3.7) kg/m(2). The most common presenting symptom was abnormal uterine bleeding with a ratio of 73% (46/63). Forty-three patients (68%, 43/63) were premenopausal, and 30% (19/63) were nulliparous. (2) Pathological features: for the endometrial cancer, 90% patients were diagnosed at stage Ⅰ, and 81% were low grade tumors (G(1)-G(2)). The histological type of endometrial cancer was mainly endometrioid carcinoma (86%) and majority (81%) of patients were proved without or with superficial myometrial invasion. For the ovarian cancer, 70% patients were diagnosed at stage Ⅰ and 65% were low grade tumors (G(1)-G(2)). Sixty-two percent of ovarian cancers were endometrioid carcinoma and 68% of patients had unilateral involvement of the ovaries. (3) Treatment and prognosis: all patients underwent surgery, of which 56 (89%) underwent staging surgery including retroperitoneal lymphadenectomy, and 57 (90%) received postoperative adjuvant therapy. The median follow-up time was 48.0 months (range, 2-176 months) , and 13% of the patients experienced tumor recurrence during the follow-up period. The median time to recurrence was 38.5 months, and 6 patients (10%) died of tumor recurrence. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) for all patients were 69% and 80%, respectively. (4) Prognostic factors: univariate analysis showed that the presence of lymphovascular space invasion (LVSI) , non-endometrioid histology of ovarian cancer and stage of ovarian cancer above stage Ⅰ were associated with significantly worse PFS (P<0.05). LVSI, high grade of endometrial cancer, and above stage Ⅰ of ovarian cancer were associated with significantly worse OS (P<0.05). On multivariate analysis, LVSI, non-endometrioid type ovarian cancer and stage of ovarian cancer above stage Ⅰwere associated with significantly worse PFS (P<0.05). In addition, LVSI and stage of ovarian cancer above stage Ⅰ were also associated with significantly worse OS (P<0.05) . Conclusions: Women with SEOC are young, premenopausal and have a favorable overall prognosis. Presence of LVSI, non-endometrioid type ovarian cancer and stage of ovarian cancer above stage Ⅰ are independent prognostic factors for PFS, and stage of ovarian cancer above stage Ⅰare independent prognostic factors for OS.

Epidemiological features and trends of endometrial cancer: 10 081 cases analysis of 62 hospitals in Guangdong province

Objective To explore the epidemiology characteristics of endometrial cancer (EC). Methods We retrospectively analyzed 10081 patients diagnosed with EC from 62 hospitals between 2000 and 2010 in Guangdong province. Results The mean age at diagnosis was 52.8±9.3. The proportion were 19.3%, 64.2%, 16.6% in patients with ages ≤45, >45-60, >60 respectively. From 2000 to 2010, the mean ages at each year were no statistic significance. The number of cases of EC were positively correlated with years(r=0.964, P<0.001). The number of cases of patients with ≤30 years old (r=0.857, P=0.001), ≤35 years old (r=0.866, P=0.001), ≤40 years old (r=0.952, P<0.001), ≤45 years old (r=0.952, P<0.001) were positively correlated with years. The ratios of patients with ≤30 years old (χ2=10.390, P=0.407), ≤35 years old (χ2=11.651, P=0.309), ≤ 40 years old (χ2=17.329, P=0.067), ≤45 years old (χ2=5.154, P=0.881) during these eleven years were no statistic significance. The ratios of type Ⅰ EC at 2000-2010 were no statistic significance. Conclusions EC often present in patients aged from >45-60 years old. The case number of EC showed an increasing trend. However, the proportion of young patients was stable. The endometroid adenocarcinoma was the main histological type of EC. Key words: Endometrial neoplasms/EP

Frequency of endometrial cancer and atypical hyperplasia in infertile women undergoing hysteroscopic polypectomy.

We aimed to determine the frequency of endometrial cancer in infertile women undergoing hysteroscopic endometrial polypectomy for endometrial polyps. A total of 1035 infertile patients who underwent office-based hysteroscopic polypectomy at Sugiyama Clinic Marunouchi between July 2011 and October 2015 were eligible for this retrospective study. All patients had been diagnosed with endometrial polyps via hysterofiberscopy prior to operation, and they underwent hysteroscopic endometrial polypectomy using a resectoscope with monopolar resection. Surgical specimens were examined histopathologically. Characteristics of patients diagnosed with endometrial cancer on histopathological examination were evaluated retrospectively. The median age of patients was 32years (range, 19-44years). On histopathological examination, endometrial cancer was found in 10 patients (0.97%). Each histological type of endometrial cancer was represented as follows: three cases of endometrioid adenocarcinoma G1; one of endometrioid adenocarcinoma G2; two of endometrioid adenocarcinoma G3; and four of atypical endometrial hyperplasia. The median age of endometrial cancer patients was 34years (range, 28-41years), and the median body mass index was 21.2kg/m2 (range, 16.7-29.9kg/m2 ). Nine endometrial cancer patients were nulliparous, and all had undergone infertility treatment, with only one woman having delivered a healthy baby. An ovulation disorder was noted in four patients, with obesity (body mass index>25kg/m2 ) in just two. Polycystic ovary syndrome was concomitantly observed in one patient. However, abnormal vaginal bleeding was not noted in any of these patients. Hysteroscopic polypectomy should be performed when endometrial polyps are detected on investigational screening, and surgical specimens should be checked for the presence of malignancy.

Outcome of endometrial cancer after lymphadenectomy: a single center retrospective analysis with long-lasting follow-up.

Role of lymphadenectomy in endometrial cancer is unclear. Our objective is to assess the role of lymphadenectomy in endometrial cancer. The study reviewed retrospectively 829 cases of endometrial cancer from a single non-oncological center from 1981 to 2014. Multivariable Cox regression analyses were performed. Independent variables were: 2009 FIGO stage, histological type of endometrial cancer (non-endometrioid, endometrioid, grading 1, 2 and 3), radicality on parametria, lymphatic dissection (any kind) (yes/no), any kind of chemotherapy, any kind of radiotherapy, brachytherapy, patients' age. Dependent variable was death for endometrial cancer and first relapse. Time variable was the semester of follow-up. P value for significance was set <0.05. Many data about the extension of node dissection were missing. Pelvic node dissection or sampling seem the more common procedure performed. At the 10-semester of follow-up, at the 20-semester of follow-up and at the 30 semester of follow up, lymphadenectomy does not improve overall survival at a p value of less than 0.05. Lymphadenectomy reduces the risk of relapse at the 10 semester and 20-semester of follow-up. Lymphadenectomy plays a role in preventing relapses but it is not proved that non-aggressive lymphadenectomy in endometrial cancer improves overall survival at p level of 0.05. Therefore, it cannot be excluded that a very small improvement in long lasting survival in few cases of endometrial cancer could be due to node dissections.

Expression of PD-1, PD-L1 and PD-L2 is associated with differentiation status and histological type of endometrial cancer.

Endometrial cancer (EC) is the most frequent gynecological malignancy and a major cause of morbidity and mortality for women worldwide. Programmed cell death protein 1 (PD-1) and its ligands programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2) have been well studied in lung cancer, melanoma and renal-cell cancer. However, few studies have been performed in EC. The purpose of the present study was to assess the expression of PD-1, PD-L1 and PD-L2 in 35 human normal endometrial tissue samples and 75 human EC tissue samples using immunohistochemical staining. It was found that 61.3% of ECs were positive for PD-1 staining, which was almost exclusively found in the tumor-infiltrating immune cells. By contrast, PD-1 was not expressed in the tumor cells or normal endometrial tissues. It was also found that 14.3% of normal endometria and 17.3% of EC tissues were positive for PD-L1 expression, while 20.0% of normal endometrium and 37.3% of EC tissues were positive for PD-L2 expression; however, there was no statistically significant difference between the normal endometrium and EC tissues. PD-1 expression in the tumor-infiltrating immune cells was more frequently found in the moderately and poorly-differentiated ECs and non-endometrioid (type II) ECs than in the well-differentiated ECs and endometrioid (type I) ECs. Similarly, PD-L1 and PD-L2 expression in the tumor-infiltrating immune cells was more frequently found in the moderately and poorly-differentiated ECs and type II ECs than in the type I ECs. The present findings indicate a possible better outcome for future treatment with anti-PD-1 or anti-PD-L1 antibody-based therapies against these subgroups of endometrial cancers with frequent expression of the PD-1/PD-L1/PD-L2 axis.

Assessment of levels of the tumor markers HE4 and CA125 considering staging, grading and histological types of endometrial cancer.

Aim of the studyAim of the study was to assess statistical differences of serum levels of HE4 and CA125 between certain endometrial cancer stages, grading and histological types.Material and methodsA retrospective study of 52 patients admitted to our clinic for a surgical operation because of endometrial cancer was performed. HE4 and CA125 were measured for each patient. The staging was done according to FIGO. The statistical difference of serum levels of tumor markers was analyzed considering different stages, grading and histological types.ResultsMost of the patients (92.31%) were post-menopausal. Serum levels of tumor markers were significantly higher among patients with stage IB-IIIC than stage IA, among patients with stages II-III than stage I and among patients with stage IIIC than stage IA-IIIB. Only HE4 was significantly higher among patients with stage IB than stage IA and among patients with grading G2 and G3 than those with G1. Only CA125 was significantly higher among patients with stage IIIA and IIIB than those with stages I and II. There was no statistically significant difference in level of either tumor marker in differentiation of endometrioid from other histological endometrial cancer.ConclusionsBoth tumor markers HE4 and CA125 can be useful additional tools for pre-surgical differentiation between different stages of endometrial cancer. HE4 can predict advanced histological grades. Neither HE4 nor CA125 can differentiate endometrioid from other histological types of endometrial cancer.

Abstract 5301: Integrative protein-marker prognostic model for early-stage endometrioid endometrial carcinoma

Abstract Endometrioid endometrial carcinoma (EEC) is the major histological type of endometrial cancer, the most prevalent gynecologic malignancy in USA. EEC recurrence or metastasis is associated with an abysmal prognosis. Early-stage EEC is generally curable, but a subset has high risk of recurrence or metastasis. Prognosis estimation for early-stage EEC mainly relies on clinicopathological characteristics, but is unreliable. We aimed to identify patients with high-risk early-stage EEC who are most likely to benefit from more extensive surgery and adjuvant therapy by building a prognostic model that integrates clinical variables and protein markers. We employed two large, independent EEC datasets as training and validation cohorts, and generated the levels of 186 proteins and phosphoproteins using reverse-phase protein arrays. Using the training samples, we developed a predictive model containing two clinical factors and 18 protein markers and optimized the risk group classification. Kaplan-Meier survival analyses in the validation cohort confirmed an improved prognostic power. Compared with clinical variables (stage, grade, and patient age), only the risk groups defined by the integrative model were consistently significant in both univariate and multivariate analyses across both cohorts. Our prognostic model is potentially of high clinical value for stratifying patients with early-stage EEC and optimizing their treatment strategies. Note: This abstract was not presented at the meeting. Citation Format: Han Liang, UT MD Anderson RPPA/TCGA working group. Integrative protein-marker prognostic model for early-stage endometrioid endometrial carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5301. doi:10.1158/1538-7445.AM2015-5301

Impact of the Lymphadenectomy in High-Risk Histologic Types of Endometrial Cancer: A Matched-Pair Study

The aim of this study is to assess the impact of lymphadenectomy (LND) on morbidity, survival, and cost for high-risk histologic types of endometrial cancer (EC). We analyzed a multicenter retrospective cohort of 389 women with high-risk histotypes of EC (poor differenced tumors [G3], clear cell, serous papillary, and mixed mesodermal tumors) preoperatively confined to the corpus and diagnosed between 2000 and 2013. All patients underwent hysterectomy and bilateral salpingo-oophorectomy. A matched-pair analysis identified 97 pairs (97 with LDN and 97 without) equal in age, body mass index, comorbidities, International Federation of Gynecology and Obstetrics stage, and adjuvant treatment. Demographic data, pathologic examination results, perioperative morbidity, and survival were abstracted from medical records. Cost was provided by the cost unit of the local hospital. Disease-free and overall survival were analyzed using the Kaplan-Meier curves and Cox multivariable regression analysis. Both study groups were homogeneous in demographic data and pathologic examination results. At a median follow-up of 24.5 months (range, 5.4-146.3), disease-free survival (hazard ratio, 1.09; 95% confidence interval, 0.70-1.90) and overall survival (hazard ratio, 0.86; 95% confidence interval, 0.56-1.33) were similar in both groups regardless of nodal count. Positive nodes were found in 23.7%. Predictor factors of nodal involvement were advanced age (P = 0.024), deep myometrial invasion (P < 0.001), and high CA 125 levels (P = 0.003). In the LDN group, operating time, late postoperative complications, and surgical cost were higher (P < 0.05). There were no statistical differences between both groups relative to surgical morbidity. Early postoperative complications and hospital stay were lower in the LDN group. The global cost was similar for both groups (6027&OV0556; for the LND group and 5772&OV0556; for the no-LND group). Lymphadenectomy in high-risk histotypes of EC does not increase perioperative morbidity or global cost and has not benefit on survival.

Cost–benefit analysis of laparoscopic surgery versus laparotomy for patients with endometrioid endometrial cancer: Experience from an institute in China

To compare the clinical outcomes and associated costs between laparoscopic and abdominal surgery for patients with endometrioid endometrial cancer. From 2003 to 2008, 115 patients who underwent laparoscopically-assisted surgery for endometrioid endometrial cancers were enrolled in this retrospective study. Another 123 patients who had abdominal surgery for the same histological type of endometrial cancer were included as the control group. The clinico-pathological variables, surgical outcome, costs, death and case recurrence of the two groups were compared. There was no difference in the patients' age, body mass index, FIGO stage, histological grade or surgical types between the two groups. The patients in the laparoscopy group had less blood loss (P = 0.010), a shorter hospital stay (P < 0.001), less postoperative pain (P < 0.001) and lower complication rates (P < 0.001) than those treated by laparotomy. The total costs in the laparoscopy group were higher than that in the laparotomy group ($2073 vs $1638, P < 0.001). Patients in the laparoscopy group returned to usual activity more quickly (P = 0.001) and went back to work earlier (P = 0.013) than those in laparotomy group. With a median follow-up of 42 months for the laparoscopy group and 40 months for the laparotomy group, there was no significant difference in the number of cases with respect to death (P = 1.000) or recurrence (P = 1.000). Laparoscopically-assisted surgery is as effective as the laparotomy approach for the treatment of early-stage and advanced-stage endometrial cancer. The relatively higher cost of the laparoscopic surgery may be compensated by its benefits. In developing countries such as China, laparoscopically-assisted surgery is also an attractive alternative for selected patients with endometrial cancer.

Abstract 1137: Racial differences in oncogene mutations detected in endometrial cancers

Abstract Endometrial cancer is the most common gynecologic cancer, with an estimated 42,000 new cases in 2010. Histologic types of endometrial cancer and stage at diagnosis differ substantially between African Americans (AA) and whites, but AA women experience poorer survival even after accounting for these factors. Additionally, other research suggests this disparity persists after controlling for co-morbid conditions, access to care, and treatment decisions. We hypothesize that there are differences in the molecular biology of tumors from white and AA women, beyond histologic type and grade, which may lead to the increased risk of death seen in AA women after an endometrial cancer diagnosis. After IRB approval, we performed a case-only retrospective analysis of patients with endometrial cancer, for whom we had tumor blocks, diagnosed from 1990-2005 at a single institution. Demographic and clinical variables were obtained from medical record review. Tumor histologic type, stage, and grade were obtained from the Metropolitan Detroit Cancer Surveillance System, part of the SEER program. Tumor histologic type and grade were confirmed by a gynecologic pathologist by slide review. We selected 150 archived tumors, including all high grade cases of any race (35 white, 40 AA), all low grade, endometroid tumors from AA women (n=44), and 31 low grade tumors from white women. Tumor DNA was extracted from formalin fixed paraffin embedded tissue using standard methods. We examined 238 mutations in 19 common oncogenes using the OncoCarta Assay v1.0 (Sequenom). Chi-square tests and Fisher's exact tests were used to assess differences in distribution of clinical and demographic variables by race or oncogene mutation status. We identified 20 mutations in 2 oncogenes in tumors from 19 women (12.7%). The most common mutation was in PIK3CA, the gene coding for the catalytic subunit p110α of PI3K, representing 15/20 (75%) of detected mutations. In PIK3CA, the following mutations were identified: R88Q in the p85-binding domain, E542K, M1043I and P539R in the helical domain, and H1047R in the kinase domain. Previous data suggest these mutations induce a gain of PI3K function and prognosis may vary by location. An additional 4 samples had activating mutations in KRAS (1 G12D, 1 G12V and 2 Q61H). No other mutations were identified. 13% of endometroid tumors harbored mutations, (11 PIK3CA and 2 KRAS). Among tumors from women with low grade endometroid cancers, race was significantly associated with harboring a mutation (p=0.04), with all 7 PIK3CA mutations were identified in AA women. All 4 KRAS mutations were found in AA women (p=0.13). This study provides preliminary evidence that the underlying molecular biology of some subtypes of histologically similar endometrial cancers differ by race. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1137. doi:10.1158/1538-7445.AM2011-1137

Abstract A111: Race is a predictor for endometrioid endometrial cancer cause-specific survival, but not all-cause survival

Abstract Endometrial cancer is the most common gynecologic cancer, with an estimated 42,000 new cases in 2010. The reported difference in overall five year survival between white women and African American (AA) women represents significant survival disparity in cancer. Histologic types of endometrial cancer and stage at diagnosis differ substantially between AAs and whites, but AA women experience poorer survival even after adjusting for these factors. After IRB approval, we performed a case-only retrospective analysis of 362 patients with surgically treated endometrioid endometrial cancer. Data from 120 AA and 242 white women, diagnosed from 1990-2005 at a single institution were analyzed to examine risk factors associated with survival. Age at diagnosis, co-morbid conditions in the 5 years prior to diagnosis, BMI, and smoking history were obtained from medical record review. Tumor histologic type, 1988 FIGO stage, grade, vital status and number of months surviving were obtained from the Metropolitan Detroit Cancer Surveillance System, part of the SEER program. Differences in stage, co-morbid conditions (using a modified Charlson Comorbidity Index, CCI), and BMI were examined by race. Chisquare tests were used to assess differences in distribution of clinical and demographic variables. Log-rank tests and Cox proportional hazards models were used to assess the risk of all-cause and endometrial cancer-related deaths. AA women were more likely than white women to have high grade tumors (p=0.009), hypertension (p=0.0005) and higher mean BMI (p=0.009). No differences by race were identified among the total group for age (p=0.98), stage at diagnosis (p=0.78), categorical modified CCI (p=0.51) or smoking history (p=0.96). When data were stratified by grade, hypertension (p=0.0009) and high BMI (p=0.002) were more frequent among AAs compared to whites with low grade tumors, but not high grade tumors. Among women with high grade tumors, AAs had a greater number of co-morbid conditions (p=0.005) and were more likely to be current or former smokers compared to whites (p=0.003). In univariate survival analysis, age at diagnosis, CCI, stage, and grade were all significantly associated with any cause survival, whereas race was not. When examining deaths due to endometrial cancer, only stage (HR=3.37,95% CI: 2.52-4.51), grade (HR=4.32,95% CI: 2.89-6.47) and race (HR=2.12,95% CI: 1.13-3.97) were predictors of survival. Analysis of endometrial cancer-related deaths by grade suggest this difference in survival by race is seen for high grade (p=0.03) but not low grade (p=0.87) tumors. In this single institution study, race was not a predictor of overall survival, but was associated with endometrial cancer-related survival. Excess of co-morbid conditions was associated with AA race, and overall survival, but not endometrial cancer-related survival in this population. A larger, more comprehensive study, including information regarding socio-economic factors, molecular tumor markers, and treatment modality is necessary to elucidate the causes underlying the large disparity in endometrial cancer survival between AA and white women. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A111.

Histopathology of endometrial hyperplasia and endometrial carcinoma

Endometrial cancer (EC) is the most common malignancy of the female genital tract in the western world. Conceptually, a dualistic model of endometrial carcinogenesis exists for sporadic EC, based on molecular findings with a good correlation to the morphologic phenotype and clinical behavior. Type 1 endometrial carcinoma represents an estrogen-related tumor, which usually arises in the setting of endometrial hyperplasia, has endometrioid histology with low grade, and tends to be biologically indolent. Grade 3 endometrioid cancers, which constitute a minority of EC, also behave aggressively. The type 2 cancers are not estrogen-driven and have a higher grade, various histologies, particularly serous carcinomas and clear-cell carcinomas, and a poorer prognosis. The diagnostic criteria of endometrial hyperplasia, endometrial in situ carcinoma, and of the different histologic types of EC, according to the most recent World Health Organization classification, are given in detail. In addition, the risk of progression of endometrial hyperplasia into endometrioid type EC and their treatment modalities are discussed. Endometrial pathologies in patients with breast cancer, receiving tamoxifen, and women affected by hereditary nonpolyposis colorectal cancer syndrome are described, including their pathogenetic aspects. Finally, a short practical description for the handling of surgical specimens from fractional curetting and hysterctomies is given.

Postmenopausal status, hypertension and obesity as risk factors for malignant transformation in endometrial polyps

Objectives We analyzed clinical data and pathological features of six cases of malignant endometrial polyps, to compare these with other examples reported in literature and to define the features of endometrial cancer arising in polyps. Moreover, to clarify the mechanisms of carcinogenesis in malignant endometrial polyps we examined the expression of cyclooxygenase-2 (COX-2), P53 and Ki 67 and their relationships with clinicopathologic characteristics. Methods The surgical pathology files of the Pathology Department of Parma University were searched for cases of endometrial polyps with nests of endometrial carcinomas, from the years 2002–2005. Clinical records, histological slides of endometrial curetting, hysterectomy with salpingo-oophorectomy specimens and pelvic lymph nodes were reviewed in each case. The main pathological features analyzed were histological types of endometrial cancer and the stage of development of neoplasm. The presence of other malignancies in the genital tract were also considered. Immunohistochemical staining was done using antibodies COX-2, p53 and Ki 67. Results In our study, all malignant endometrial polyps had been detected in postmenopausal women. The majority of our patients with malignant endometrial polyps had risk factors for the development of endometrial carcinoma such as hypertension, obesity and unopposed estrogen therapy. Unlike other studies, no patients had a history of previous breast carcinoma and Tamoxifen treatment. The most common subtypes of endometrial carcinoma in malignant polyps are endometrioid carcinoma and serous papillary carcinoma. Endometrial carcinoma arising in endometrial polyps is an early endometrial carcinoma with good prognosis, except for papillary serous carcinoma, which can be associated with multiple omental involvement, despite low stage of development in the uterus. Immunohistochemical study showed that COX-2 expression was found in cytoplasm of tumor cells and this was elevated in all cases, independently of the grade and the stage of development of the malignancy, histological subtype and deep invasion of myometrium. P53 and Ki 67 expression, detected in the nuclei of neoplastic cells, was not correlated with COX-2 immunoreactivity, but these markers were associated with more advanced stage, grading, and histologic subtypes of tumor. Conclusions Postmenopausal status, hypertension, obesity could all be considered as risk factors for carcinomatous transformation within endometrial polyps in women without a history of breast carcinoma and Tamoxifen treatment. However, our series is small (only six cases considered) and further studies are necessary to confirm this hypothesis. In the current study, immunohistochemical data reveal that COX-2 expression may be associated with the carcinogenesis in endometrial carcinomas arising in endometrial polyps, but this antibody is not correlated with tumor aggressiveness, P53 and Ki 67 expression. P53 and Ki 67 overexpression, instead, are associated with advanced stage, histologic subtype and deep myometrial invasion of neoplasm.

Molecular pathology of endometrial carcinoma: transcriptional signature in endometrioid tumors.

A dualistic model, which has been established on a morphological basis and that differentiates type I endometrioid from type II non-endometrioid endometrial cancer, is widely accepted. Molecular genetics have provided us with data supporting the dualistic model of endometrial tumorigenesis and with some clues to speculate about the sequence of the molecular alterations defining the tumorigenesis pathways. In type I endometrioid endometrial cancer, PTEN gene silencing, microsatellite instability associated with defects in DNA mismatch repair genes, or mutations in the K-ras gene are the known major alterations defining the progression from normal endometrium to hyperplasia and then on to carcinoma. Recently, cDNA microarray technology for identifying the differences in gene expression patterns between the histological types of endometrial cancer have permitted the identification of differentially expressed genes that could help us to understand differences in the biology and the clinical outcome between histiotypes. Genes involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, or altered genes associated with the initial steps of myometrial infiltration in endometrioid endometrial cancer, represent examples of how useful large genetic screenings can be for understanding the tumorigenesis process and the future directions in the molecular pathogenesis of endometrial cancer.

Microarray Analysis of Endometrial Carcinomas and Mixed Mullerian Tumors Reveals Distinct Gene Expression Profiles Associated with Different Histologic Types of Uterine Cancer

Previous studies using cDNA microarray have indicated that distinct gene expression profiles characterize endometrioid and papillary serous carcinomas of the endometrium. Molecular studies have observed that mixed mullerian tumors, characterized by both carcinomatous and sarcomatous components, share features that are characteristic of endometrial carcinomas. The objective of this analysis was to more precisely define gene expression patterns that distinguish endometrioid and papillary serous histologies of endometrial carcinoma and mixed mullerian tumors of the uterus. One hundred nineteen pathologically confirmed uterine cancer samples were studied (66 endometrioid, 24 papillary serous, and 29 mixed mullerian tumors). Gene expressions were analyzed using the Affymetrix Human Genome Arrays U133A and U133B Genechip set. Unsupervised analysis revealed distinct global gene expression patterns of endometrioid, papillary serous, mixed mullerian tumors, and normal tissues as grossly separated clusters. Two-sample t tests comparing endometrioid and papillary serous, endometrioid and mixed mullerian tumor, and papillary serous and mixed mullerian tumor pairs identified 1,055, 5,212, and 1,208 differentially expressed genes at P < 0.001, respectively. These data revealed that distinct patterns of gene expression characterize various histologic types of uterine cancer. Gene expression profiles for select genes were confirmed using quantitative PCR. An understanding of the molecular heterogeneity of various histologic types of endometrial cancer has the potential to lead to better individualization of treatment in the future.