Content uploaded by Ashley S Felix
Author content
All content in this area was uploaded by Ashley S Felix
Content may be subject to copyright.
A preview of the PDF is not available
Factors associated with Type I and Type II endometrial cancer
Abstract
We investigated risk factors for Type II (n = 176) vs. Type I (n = 1,576) endometrial cancer (EC) in cases treated at Magee-Womens Hospital between 1996 and 2008.
Clinical data were available from the University of Pittsburgh Medical Center (UPMC) Network Cancer Registry. Logistic regression was used to estimate the adjusted odds of having Type II EC vs. Type I EC. Risk factors of interest in this analysis were age, race, body mass index (BMI), year of diagnosis, parity, menopausal status, and history of additional primary tumors.
Relative to women with Type I EC, women with Type II EC were more likely to be older at diagnosis (OR: 1.03 per 1 year increase in age, 95% CI 1.01-1.05), of non-white race (OR: 2.95, 95% CI 1.66-5.27), have a history of additional primary tumors (OR: 1.56, 95% CI 1.05-2.32), and less likely to be obese (OR: 0.45, 95% CI 0.29-0.70).
In this large retrospective cohort of patients with EC, the striking difference in risk factors associated with Type II vs. Type I tumors suggests that these subtypes represent different disease entities that require different treatment modalities. Currently, Type II cases have a significantly worse prognosis compared to Type I. Further characterization of risk factors associated with developing Type II tumors is needed to prevent this aggressive malignancy.
... Disparities in endometrial cancer were also highlighted among women of different races whereby White women are more frequently diagnosed with endometrial cancer compared to women of other races [33]. However, Black women tend to have more advanced stages and aggressive tumors of endometrial cancer compared to White women [33,34]. Similarly, the risk of death attributed to endometrial cancer among Black women was shown to be 2.5 times higher than that of White women, and the disease-specific mortality rate of endometrial cancer among women of Black race was reported as 9.2 per 100,000 compared to 4.6 per 100,000 for women of White race [35]. ...
Background
Endometrial cancer is one of the most common types of cancer that affects women’s reproductive system. The risk of endometrial cancer is associated with biologic, behavioral and social determinants of health (SDOH). The focus of the work is to investigate the cumulative effect of this cluster of covariates on the odds of endometrial cancer that heretofore have only been considered individually.
Methods
We conducted a quantitative study using the Behavioral Risk Factor Surveillance System (BRFSS) national data collected in 2020. Data analysis using weighted Chi-square test and weighted logistic regression were carried out on 84,118 female study participants from the United States.
Results
Women with diabetes mellitus were approximately twice as likely to have endometrial cancer compared to women without diabetes (OR 1.54; 95%CI: 1.01–2.34). Biologic factors that included obesity (OR 3.10; 95% CI: 1.96–4.90) and older age (with ORs ranging from 2.75 to 7.21) had a significant increase in the odds of endometrial cancer compared to women of normal weight and younger age group of 18 to 44. Among the SDOH, attending college (OR 1.83; 95% CI: 1.12-3.00) was associated with increased odds of endometrial cancer, while renting a home (OR 0.50; 95% CI: 0.28–0.88), having other arrangements (OR 0.05; 95% CI: 0.02–0.16), being divorced (OR 0.55; 95% CI: 0.30–0.99), and having higher incomes ranging from $35,000 to $50,000 (OR 0.35; 95% CI: 0.16–0.78), and above $50,000 (OR 0.29; 95% CI: 0.14–0.62), were all associated with decreased odds of endometrial cancer. As for race, Black women (OR 0.24; 95% CI: 0.07–0.84) and women of other races (OR 0.37; 95% CI: 0.15–0.88) were shown to have lower odds of endometrial cancer compared to White women.
Conclusion
Our results revealed the importance of adopting a comprehensive approach to the study of the associated factors of endometrial cancer by including social, biologic, and behavioral determinants of health. The observed social inequity in endometrial cancer among women needs to be addressed through effective policies and changes in social structures to advocate for a standardized healthcare system that ensures equitable access to preventive measures and quality of care.
... This type is associated with long-lasting, noncompetitive estrogenic stimulation and is often preceded by endometrial hyperplasia [34]. Endometriosis is also an estrogen-dependent disease, as is type I endometrial cancer [35,36]. Endometriosis shares many of the key features, such as resistance to apoptosis, stimulation of angiogenesis, invasion, and inflammation, with cancer [26]. ...
Simple Summary
Previous studies have shown that women with endometriosis have an increased risk of ovarian cancer. However, it is unclear whether endometriosis is associated with a risk of developing endometrial cancer. Therefore, this study was designed to retrospectively assess the clinicopathological relationship between endometrial cancer and endometriosis using the medical records of patients with endometrial cancer who underwent surgery at our institution.
Abstract
Endometriosis is known to be associated with an increased risk of endometrioid and clear cell ovarian cancer. However, the association between endometriosis and endometrial cancer is controversial. Therefore, we retrospectively analyzed the medical records of women with endometrial cancer who had undergone surgery at our institution to evaluate the clinicopathological relationship between endometrial cancer and endometriosis. The study included 720 women pathologically diagnosed with endometrial cancer at our hospital between 2000 and 2020. The participants were allocated to two groups of patients with endometrial cancer: patients with endometriosis (n = 101) and patients without endometriosis (n = 619). Endometrial cancer patients with endometriosis were significantly younger (median age 54.0 vs. 58.0; p = 0.002). In addition, endometrial cancer patients with endometriosis had fewer pregnancies and deliveries (median pregnancy 1.58 vs. 1.99; p = 0.019, median delivery 1.25 vs. 1.56; p = 0.012). The percentage of patients classified as stage IA was significantly higher in those with endometrial cancer with endometriosis (68.3% vs. 56.4%; p = 0.029). In the analysis of synchronous ovarian cancer, the percentage of dual primary cancer was higher in patients with endometriosis (14.9% vs. 1.6%; p < 0.001). The association of young-onset early-stage endometrial cancer with endometriosis is an important finding that cannot be ignored clinically.
Introdução: O câncer endometrial uterino é a malignidade ginecológica mais prevalente em mulheres brasileiras e uma das principais causas de morbidade e mortalidade. Mais de 60.000 novos casos são esperados durante o próximo ano, devido à crescente exposição da população aos fatores de risco sabidamente associados à neoplasia, como obesidade e sedentarismo. O diagnóstico e tratamento da neoplasia de endométrio são complexos e onerosos do ponto de vista de saúde pública, portanto, a prevenção primária é um pilar fundamental do manejo da condição. Objetivo: Este estudo tem como objetivo conhecer a prevalência de fatores associados ao câncer de endométrio em mulheres na pré e pós menopausa atendidas em um Centro Integrado Ambulatorial em Brasília. Metodologia: Foi realizado um estudo transversal e descritivo entre as mulheres atendidas no setor de Ginecologia de um Centro Ambulatorial de Atenção Primária. Foram coletados dados relativos às variáveis sociodemográficas, gineco-obstétricas e exposição a fatores associados ao câncer endometrial. As participantes assinaram o termo de consentimento livre e esclarecido e o estudo seguiu as normas da resolução 196/96. RESULTADOS: A população foi composta por 106 mulheres. Dentre os fatores de risco conhecidos para o desenvolvimento do câncer de endométrio, encontrou-se a prevalência aumentada de mulheres com sobrepeso (41,5% das amostras) ou obesidade (29,2%), primigestas (41,1%) e nuligestas (30,1%). CONCLUSÃO: A prevalência elevada de alguns fatores aponta para a necessidade da implementação de medidas de prevenção e promoção à saúde com o objetivo de se reduzir a exposição das pacientes da área atendidas aos fatores associados ao câncer.
While the progressive histologic steps leading to endometrial cancer (EndoCA), the most common female reproductive tract malignancy, from endometrial hyperplasia are well-established, the molecular changes accompanying this malignant transformation in a single patient have never been described. We had the unique opportunity to investigate the paired histologic and molecular features associated with the 12-year development of EndoCA in a postmenopausal female who could not undergo hysterectomy and instead underwent progesterone treatment. Using a specially-designed 58 gene next-generation sequencing panel, we analyzed a total of 10 sequential biopsy samples collected over this time frame. A total of eight pathogenic/likely pathogenic mutations in seven genes, APC, ARID1A, CTNNB1, CDKN2A, KRAS, PTEN and TP53, were identified. A PTEN nonsense mutation p.W111* was present in all samples analyzed except histologically normal endometrium. Apart from this PTEN mutation, the only other recurrent mutation was KRAS G12D; present in four biopsy samplings, including histologically normal tissue obtained at the patient's first visit but not detectable in the cancer. The PTEN p.W111* mutant allele fractions were lowest in benign, inactive endometrial glands (0.7%), highest in adenocarcinoma (36.9%) and notably, were always markedly reduced following progesterone treatment. To our knowledge, this report provides the first molecular characterization of EndoCA development in a single patient. A single PTEN mutation was present throughout the 12 years of cancer development. Importantly, and with potential significance towards medical and non-surgical management of EndoCA, progesterone treatments were consistently noted to markedly decrease PTEN mutant allele fractions to pre-cancerous levels.
Understanding the etiology, presentation, evaluation, and management of selected non-endometrioid endometrial adenocarcinomas of the uterine corpus is needed to define optimal treatment regimens.
The pathology and treatment of selected non-endometrioid endometrial adenocarcinomas of the uterus are reviewed and summarized.
The most common non-endometrioid histology is papillary serous (10%), followed by clear cell (2% to 4%), mucinous (0.6% to 5%), and squamous cell (0.1% to 0.5%). Some non-endometrioid endometrial carcinomas behave more aggressively than the endometrioid cancers such that even women with clinical stage I disease often have extrauterine metastasis at the time of surgical evaluation. Therefore, when technically and medically feasible, comprehensive surgical staging is helpful for women with non-endometrioid endometrial cancer histology. Comprehensive surgical staging includes hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, and cytological evaluation of the abdominal cavity. While whole abdominal radiotherapy has a limited role in early-stage uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CC), there may be a role for postoperative chemotherapy and volume-directed radiotherapy in both early-stage UPSC and CC. In the setting of optimally debulked advanced-stage disease, a combination of radiation and chemotherapy may be indicated. In the setting of recurrent disease or in women with residual disease after surgery, a platinum-based regimen or enrollment in a clinical trial is recommended.
UPSC and CC are managed similarly since sufficient data to separate treatment recommendations are lacking. Because both histologies are associated with a high rate of recurrence, adjuvant therapy is recommended even in women with early-stage disease. The remaining cell types should be treated similar to endometrioid or other low-grade histologies.
Histopathologic diagnosis of endometrial biopsies is used to estimate the risk of progression to carcinoma and guide clinical management. Problems with the widely used World Health Organization (WHO) system for classifying endometrial hyperplasia (EH) have prompted the development of an alternative system based on endometrial intraepithelial neoplasia (EIN). The authors estimated progression risk associated with EIN among endometrial biopsies in a nested case-control study of EH progression.
Index biopsies with original community pathology diagnoses of disordered proliferative endometrium (DPEM) or EH that were independently confirmed by a panel of pathologists were independently reviewed and assigned EIN classifications (inadequate, benign, EIN, or cancer) by a second panel of pathologists. Cases (N = 138) progressed to carcinoma at least 1 year (median, 6 years) after their index biopsy. Controls (N = 241) also had EH, did not progress to carcinoma, and were individually matched to cases based on age at EH, date of EH, and length of follow-up. By using conditional logistic regression, the authors estimated relative risks (RRs) with 95% confidence intervals (95% CIs) for progression to carcinoma for EIN versus benign.
In the EIN system, 71 (52.6%) cases and 159 (66.8%) controls were classified as benign and 42 (31.1%) cases and 65 (27.3%) controls were classified as EIN. The RR for EIN versus benign was 7.76 (95% CI, 3.36-17.91). In the WHO system, the RR for atypical hyperplasia (AH) versus DPEM, simple hyperplasia, or complex hyperplasia was 9.19 (95% CI, 3.87-21.83).
Among women observed for at least 1 year after receiving a biopsy-based EH diagnosis, EIN and AH were both found to have similarly increased risks of progression to carcinoma.
A review of 256 cases of pathologic Stage I uterine adenocarcinoma treated at Stanford University Hospital revealed 26 cases of uterine papillary serous carcinoma (UPSC), a clinically aggressive and morphologically distinct variant of adenocarcinoma which closely resembles ovarian papillary serous carcinoma. These lesions are easily recognized by microscopic examination and typically feature a high degree of cytologie anaplasia and a papillary growth pattern. Invasion of the lymphatics has been a frequent finding. The relapse rate among patients with pathologic Stage I UPSC was 50% (13/26), five times the rate which would have been predicted by the incidence of UPSC. Patients with Stage I UPSC fared significantly worse than the group of nonpapillary grade II or grade III adenocarcinomas (p < 0.0001). Forty percent of Stage I UPSC patients had deep myometrial invasion, as compard with 12% of those with all other histologic types of adenocarcinoma (p p = 0.001). Women with UPSC deeply invading the myometrium tended to do worse than those with deeply invasive lesions of the more usual endometrioid type as reflected by relapse rates (after surgery alone) of 63% and 30%, respectively. Of seven Stage I corpus carcinoma patients whose initial site of failure was in the upper abdomen, six had UPSC. Thus, UPSC shares the tendency of its ovarian counterpart to spread over peritoneal surfaces. In addition to the original study group of 26 Stage I patients, 34 patients with more advanced stages of UPSC were also reviewed. Of these, 26 have been followed and four survive. Eleven of these women presented or relapsed with abdominal carcinomatosis. UPSC is a clinically aggressive neoplasm which should be distinguished from other types of primary endometrial adenocarcinoma. In cases of invasive UPSC the mode of spread, similar to that of ovarian surface epithelial carcinomas, suggests the need for adjuvant upper abdominal and pelvic irradiation or effective chemotherapy.
BACKGROUND
The two most common types of uterine endometrial carcinoma, endometrioid (UEC) and serous (USC), differ in their histopathologic appearance and biologic behavior. Recent studies suggest that these differences may be associated with distinct molecular genetic alterations.METHODS
In the current study, the authors compared the frequencies of K-ras and p53 mutations and microsatellite instability (MI) between UEC and USC by analyzing all 3 molecular genetic changes in one set of tumors. Furthermore, the distribution of these molecular genetic alterations was determined among UECs of different histopathologic grade. The authors analyzed 58 UECs with known MI status for K-ras and p53 mutations. The K-ras and p53 genes were analyzed in 45 and 6 cases of USC, respectively. These results were combined with previous data on p53 mutations (21 cases) and MI (34 cases) in USC.RESULTSMI was present in 16 of 57 UECs (28%) but in none of 34 USCs. p53 mutations were found in 7 of 42 UECs (17%) and 25 of 27 USCs (93%) by direct sequencing of exons 5–8. UECs and USCs with p53 mutations showed strong immunoreactivity for p53 in about 85% of the cases, whereas about 15% of the cases were immunonegative. K-ras mutations at codon 12 were found in 15 of 58 UECs (26%) and in only 1 of 45 USC (2%) by dot blot oligohybridization after polymerase chain reaction amplification of exon 1. Notably, the frequency of both K-ras and p53 mutations and MI was significantly different between UEC and USC (P < 0.001). In UECs, MI and K-ras mutations occurred in low grade as well as in high grade tumors, whereas p53 mutations were present almost exclusively in high grade tumors.CONCLUSIONS
The results of this study suggest that different molecular genetic pathways are involved in the pathogenesis of UEC and USC and that low grade UEC may progress to high grade UEC. These findings support the hypothesis that UEC and USC are separate entities and suggest that different molecular genetic alterations may be responsible for their distinct morphology and biologic behavior. Cancer 2000;88:814–24. © 2000 American Cancer Society.
Stage I-II uterine papillary serous carcinoma (UPSC) patients have a significant risk for extrapelvic recurrence. However, clinicopathologic risk factors for recurrence are not well understood. This study was undertaken to define the prognostic factors for recurrence and survival in patients with early-stage UPSC.
A retrospective, multi-institution analysis of surgically staged I-II UPSC patients was performed. Patients were treated by various adjuvant modalities. Age, race, sub-stage, percentage UPSC histology, lymphvascular space invasion (LVSI), tumor size and adjuvant treatment modality were evaluated for their effect on recurrence and survival outcomes.
We identified 206 patients. Forty patients (19.4%) had 5-49% UPSC, 55 (26.7%) had 50-99% and 111 patients (53.9%) had 100% UPSC in their respective uterine specimens. Twenty one percent of patients experienced a primary recurrence. On univariate analysis, age, increasing %UPSC, LVSI, and tumor size were not significantly associated with recurrence or progression-free survival (PFS). However, substage (p=0.005) and treatment with platinum/taxane-based chemotherapy (p=0.001) were associated with recurrence/PFS. On multivariate analysis, only chemotherapy (p=0.01) was a significant factor affecting PFS, whereas age (p=0.05), substage (p=0.05), and chemotherapy (p=0.02) were associated with overall survival.
Traditional risk factors for recurrence and survival in patients with early-stage endometrial cancer may not be relevant in patients with UPSC. Patients with any percentage UPSC in their uterine specimens are at a significant risk for recurrence and poor survival outcomes. Given that current clinicopathologic data does not accurately identify women most likely to benefit from adjuvant therapy, alternative prognostic markers based on novel techniques should be explored.
Objective:
Uterine papillary serous carcinoma (UPSC) is a clinically and pathologically distinct subtype of endometrial cancer. Although less common than its endometrioid carcinoma (EEC) counterpart, UPSC accounts for a disproportionate number of endometrial cancer related deaths. To date, limited prospective trials exist from which evidence-based management can be developed. This review summarizes the available literature concerning UPSC in an effort to provide the clinician with information pertinent to its management.
Methods:
MEDLINE was searched for all research articles published in English between January 1, 1966 and May 1, 2009 in which the studied population included women diagnosed with UPSC. Although preference was given to prospective studies, studies were not limited by design or by numbers of subjects given the paucity of available reports.
Results:
UPSC is morphologically and genetically different from EEC. Women often present with postmenopausal vaginal bleeding, but may also present with abnormal cervical cytology, ascites, or a pelvic mass. In some cases, the diagnosis may be made with endometrial biopsy, while in other cases it is not made until the time of definitive surgery. Metastatic disease is common and best identified via comprehensive surgical staging. Local and distant recurrences occur frequently, with extra-pelvic relapses reported most commonly. Optimal cytoreduction and adjuvant platinum/taxane-based chemotherapy appear to improve survival, while adjuvant radiotherapy may contribute to loco-regional disease control.
Conclusions:
Women diagnosed with UPSC should undergo comprehensive surgical staging and an attempt at optimal cytoreduction. Platinum/taxane-based adjuvant chemotherapy should be considered in the treatment of both early- and advanced-stage patients. Careful long-term surveillance is indicated as many of these women will recur. Prospective clinical trials of women with UPSC are necessary in order to delineate the optimal therapy for women with newly diagnosed and recurrent disease.
Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Incidence and death rates are standardized by age to the 2000 United States standard million population. A total of 1,479,350 new cancer cases and 562,340 deaths from cancer are projected to occur in the United States in 2009. Overall cancer incidence rates decreased in the most recent time period in both men (1.8% per year from 2001 to 2005) and women (0.6% per year from 1998 to 2005), largely because of decreases in the three major cancer sites in men (lung, prostate, and colon and rectum [colorectum]) and in two major cancer sites in women (breast and colorectum). Overall cancer death rates decreased in men by 19.2% between 1990 and 2005, with decreases in lung (37%), prostate (24%), and colorectal (17%) cancer rates accounting for nearly 80% of the total decrease. Among women, overall cancer death rates between 1991 and 2005 decreased by 11.4%, with decreases in breast (37%) and colorectal (24%) cancer rates accounting for 60% of the total decrease. The reduction in the overall cancer death rates has resulted in the avoidance of about 650,000 deaths from cancer over the 15-year period. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, education, geographic area, and calendar year. Although progress has been made in reducing incidence and mortality rates and improving survival, cancer still accounts for more deaths than heart disease in persons younger than 85 years of age. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population and by supporting new discoveries in cancer prevention, early detection, and treatment.
Endometrial carcinoma is the most common cancer of the lower female genital tract in the USA. Various factors, including age, body mass index, race, disease stage, diabetes, histology, tumor grade and other comorbid conditions were associated with endometrial carcinoma mortality in previous case-control and cross-sectional studies not involving tumor registries. Cancer registries are important sources of data on endometrial cancer; however, they are rarely utilized in current research projects. The purpose of this study was to analyze factors associated with endometrial cancer mortality in the University of Pittsburgh Medical Center (UPMC) Magee Cancer Registry (PA, USA).
Data were obtained from the UPMC cancer registry from 1996 to 2007. A total of 1614 cases were identified using the Honest Broker system at Magee Womens Hospital. Key factors involved in endometrial cancer mortality were identified through survival analysis.
Among the characteristics available from the cancer registry, the following were the main ones associated with endometrial cancer mortality: race, stage, chemotherapy, parity and lymph node involvement.
This is one of the first studies that reported factors influencing endometrial cancer mortality in patients residing in Pittsburgh area. An improved understanding of risk factors associated with endometrial cancer morbidity and mortality may hold a key to better preventive strategies for endometrial carcinoma, especially for women in high-risk groups.