Article

Absolute Risk of Endometrial Carcinoma During 20-Year Follow-Up Among Women With Endometrial Hyperplasia

University of Maryland, Baltimore, Baltimore, Maryland, United States
Journal of Clinical Oncology (Impact Factor: 17.88). 02/2010; 28(5):788-92. DOI: 10.1200/JCO.2009.24.1315
Source: PubMed

ABSTRACT PURPOSE The severity of endometrial hyperplasia (EH)-simple (SH), complex (CH), or atypical (AH)-influences clinical management, but valid estimates of absolute risk of clinical progression to carcinoma are lacking. Materials and METHODS We conducted a case-control study nested in a cohort of 7,947 women diagnosed with EH (1970-2002) at one prepaid health plan who remained at risk for at least 1 year. Patient cases (N = 138) were diagnosed with carcinoma, on average, 6 years later (range, 1 to 24 years). Patient controls (N = 241) were matched to patient cases on age at EH, date of EH, and duration of follow-up, and they were counter-matched to patient cases on EH severity. After we independently reviewed original slides and medical records of patient controls and patient cases, we combined progression relative risks (AH v SH, CH, or disordered proliferative endometrium [ie, equivocal EH]) from the case-control analysis with clinical censoring information (ie, hysterectomy, death, or left the health plan) on all cohort members to estimate interval-specific (ie, 1 to 4, 5 to 9, and 10 to 19 years) and cumulative (ie, through 4, 9, and 19 years) progression risks. Results For nonatypical EH, cumulative progression risk increased from 1.2% (95% CI, 0.6% to 1.9%) through 4 years to 1.9% (95% CI, 1.2% to 2.6%) through 9 years to 4.6% (95% CI, 3.3% to 5.8%) through 19 years after EH diagnosis. For AH, cumulative risk increased from 8.2% (95% CI, 1.3% to 14.6%) through 4 years to 12.4% (95% CI, 3.0% to 20.8%) through 9 years to 27.5% (95% CI, 8.6% to 42.5%) through 19 years after AH. CONCLUSION Cumulative 20-year progression risk among women who remain at risk for at least 1 year is less than 5% for nonatypical EH but is 28% for AH.

Download full-text

Full-text

Available from: Máire A Duggan, Jun 24, 2015
0 Followers
 · 
126 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The most prevalent uterine tumours are leiomyomas, which are benign and have a prevalence of about 50% at menopause. The incidence of endometrial cancer and uterine sarcomas is about 25 per 100,000 and 0.7 per 100,000, respectively. Reported risk factors for endometrial cancer are advanced age, unopposed oestrogen stimulation, late menopause, obesity, diabetes mellitus, nulliparity, feminising ovarian tumours, polycystic ovarian syndrome, tamoxifen and belonging to a hereditary non-polyposis colorectal cancer family. Unopposed oestrogen stimulation and tamoxifen have also been confirmed to induce uterine sarcomas. Cervical cytology, endometrial sampling and ultrasound have been proposed in the early diagnosis of endometrial cancer. No pathognomonic ultrasound, magnetic resonance imaging or computed tomography features are able to differentiate between a leiomyoma and a uterine sarcoma, and reliable serum markers for sarcomas are lacking. To date, mass screening for uterine malignancies is not feasible or effective.
    Best practice & research. Clinical obstetrics & gynaecology 11/2011; 26(2):257-66. DOI:10.1016/j.bpobgyn.2011.08.002 · 3.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Because of the frequent detection of carcinoma in surgical specimens after hysterectomy for endometrial complex atypical hyperplasia (CAH), it has been suggested that patients with a preoperative diagnosis of CAH be referred to gynecologic oncology for potential lymphadenectomy. However, the risk of lymph node metastasis in such patients is unknown. We sought to determine the risk of endometrial cancer and to estimate the risk of lymphatic spread in women with a preoperative diagnosis of CAH. Study Design We retrospectively reviewed the medical records of 150 consecutive patients with a preoperative diagnosis of CAH who subsequently underwent hysterectomy. Clinical characteristics and pathologic information were abstracted. Risk of lymphatic spread was modeled using previously published criteria and nomograms. Results Fifty-five of the 150 patients (36.7%) had an incidental endometrial carcinoma at the time of hysterectomy. Among patients with a preoperative office biopsy compared to dilation and curettage, the rate of an incidental finding of cancer was 43.5% and 28.1%, respectively (p = 0.054). Of patients with cancer, 1 (1.8%) had a grade 3 endometrial carcinoma, 4 (7.3%) had lymphovascular space involvement, and 6 (10.9%) had deep (> 50%) myometrial invasion. For the 10 patients who underwent lymphadenectomy, one (10%) had lymph node metastases. Based on multiple models, the estimated risk of lymph node spread was 1.6-2.1% for all women with a preoperative diagnosis of CAH and 4.4-6.8% for the 55 women with endometrial cancer. Conclusions Given the high rates of underlying endometrial cancer and the potential need for lymphadenectomy, care for patients with a preoperative diagnosis of CAH desiring definitive management with hysterectomy should be referred to a gynecologic oncologist.
    Gynecologic Oncology 10/2014; 135(3). DOI:10.1016/j.ygyno.2014.10.008 · 3.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is linked to increased incidence of endometrioid endometrial cancer (EEC) and complex atypical hyperplasia (CAH). We here explore pattern and sequence of molecular alterations characterizing endometrial carcinogenesis in general and related to body mass index (BMI), to improve diagnostic stratification and treatment strategies. We performed molecular characterization of 729 prospectively collected EEC and CAH. Candidate biomarkers were identified in frozen samples by whole-exome and Sanger sequencing, oligonucleotide gene expression and Reverse Phase Protein Arrays (investigation cohort) and further explored in formalin fixed tissues by immunohistochemistry and Fluorescent in Situ Hybridization (validation cohort). We here demonstrate that PIK3CA mutations, PTEN loss, PI3K and KRAS activation are early events in endometrial carcinogenesis. Molecular changes related to KRAS activation and inflammation are more common in obese CAH patients, suggesting different prevention and systemic treatment strategies in obese and non-obese patients. We also found that oncoprotein Stathmin might improve preoperative diagnostic distinction between premalignant and malignant endometrial lesions.
    Oncotarget 11/2014; · 6.63 Impact Factor