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Endometrial (Uterus) Cancer

Endometrial cancer is a malignancy of the endometrium (the inner lining of the uterus, or womb) and is the most common gynaecological cancer, and accounts for 13% of all cancers in women. It is most frequently in women over age 50. A know risk factor is prior oestrogen-replacement therapy (however, oestrogen replacement also lowers risk of heart disease). Symptoms can include pelvic pain, and blood-soaked discharge - though these are also common symptoms related to menopausal changes.

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  • PubMed search for publications about Endometrial Cancer - Limit search to: [Reviews]

    PubMed Central search for free-access publications about Endometrial Cancer
    MeSH term: Endometrial Neoplasms
    International US National Library of Medicine
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Dashti SG, Chau R, Ouakrim DA, et al.
Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome.
JAMA. 2015; 314(1):61-71 [PubMed] Related Publications
IMPORTANCE: Apart from hysterectomy, there is no consensus recommendation for reducing endometrial cancer risk for women with a mismatch repair gene mutation (Lynch syndrome).
OBJECTIVE: To investigate the association between hormonal factors and endometrial cancer risk in Lynch syndrome.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study included 1128 women with a mismatch repair gene mutation identified from the Colon Cancer Family Registry. Data were analyzed with a weighted cohort approach. Participants were recruited between 1997 and 2012 from centers across the United States, Australia, Canada, and New Zealand.
EXPOSURES: Age at menarche, first and last live birth, and menopause; number of live births; hormonal contraceptive use; and postmenopausal hormone use.
MAIN OUTCOMES AND MEASURES: Self-reported diagnosis of endometrial cancer.
RESULTS: Endometrial cancer was diagnosed in 133 women (incidence rate per 100 person-years, 0.29; 95% CI, 0.24 to 0.34). Endometrial cancer was diagnosed in 11% (n = 70) of women with age at menarche greater than or equal to 13 years compared with 12.6% (n = 57) of women with age at menarche less than 13 years (incidence rate per 100 person-years, 0.27 vs 0.31; rate difference, -0.04 [95% CI, -0.15 to 0.05]; hazard ratio per year, 0.85 [95% CI, 0.73 to 0.99]; P = .04). Endometrial cancer was diagnosed in 10.8% (n = 88) of parous women compared with 14.4% (n = 40) of nulliparous women (incidence rate per 100 person-years, 0.25 vs 0.43; rate difference, -0.18 [95% CI, -0.32 to -0.04]; hazard ratio, 0.21 [95% CI, 0.10 to 0.42]; P < .001). Endometrial cancer was diagnosed in 8.7% (n = 70) of women who used hormonal contraceptives greater than or equal to 1 year compared with 19.2% (n = 57) of women who used contraceptives less than 1 year (incidence rate per 100 person-years, 0.22 vs 0.45; rate difference, -0.23 [95% CI, -0.36 to -0.11]; hazard ratio, 0.39 [95% CI, 0.23 to 0.64]; P < .001). There was no statistically significant association between endometrial cancer and age at first and last live birth, age at menopause, and postmenopausal hormone use.
CONCLUSIONS AND RELEVANCE: For women with a mismatch repair gene mutation, some endogenous and exogenous hormonal factors were associated with a lower risk of endometrial cancer. These directions and strengths of associations were similar to those for the general population. If replicated, these findings suggest that women with a mismatch repair gene mutation may be counseled like the general population in regard to hormonal influences on endometrial cancer risk.

Kuna K, Grbavac I, Vuković A, et al.
Coexistence of ruptured ectopic tubal pregnancy, dermoid and endometriotic cyst with tubo-ovarian abscess in the same adnexa: case report.
Acta Clin Croat. 2015; 54(1):103-6 [PubMed] Related Publications
A 32-year-old pregnant woman presented to the hospital with abdominal pain and minimal vaginal bleeding. Transvaginal ultrasound revealed visible fluid in pelvic region with suspected tubal rupture, and subsequently laparoscopy was performed. During laparoscopy, additional gynecologic pathologies were noticed. Histopathologic finding showed dermoid and endometriotic cyst, as well as tubo-ovarian abscess in the same adnexa. This case report highlights the necessity of considering multiple diagnoses in the same organic system, which may be encountered by surgeon and histopathologist.

Filomeno M, Bosetti C, Bidoli E, et al.
Mediterranean diet and risk of endometrial cancer: a pooled analysis of three Italian case-control studies.
Br J Cancer. 2015; 112(11):1816-21 [PubMed] Related Publications
BACKGROUND: Some components of the Mediterranean diet have favourable effects on endometrial cancer, and the Mediterranean diet as a whole has been shown to have a beneficial role on various neoplasms.
METHODS: We analysed this issue pooling data from three case-control studies carried out between 1983 and 2006 in various Italian areas and in the Swiss Canton of Vaud. Cases were 1411 women with incident, histologically confirmed endometrial cancer, and controls were 3668 patients in hospital for acute diseases. We measured the adherence to the Mediterranean diet using a Mediterranean Diet Score (MDS), based on the nine dietary components characteristics of this diet, that is, high intake of vegetables, fruits/nuts, cereals, legumes, fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) for increasing levels of the MDS (varying from 0, no adherence, to 9, maximum adherence) using multiple logistic regression models, adjusted for major confounding factors.
RESULTS: The adjusted OR for a 6-9 components of the MDS (high adherence) compared with 0-3 (low adherence) was 0.43 (95% CI 0.34-0.56). The OR for an increment of one component of MDS diet was 0.84 (95% CI 0.80-0.88). The association was consistent in strata of various covariates, although somewhat stronger in older women, in never oral contraceptive users and in hormone-replacement therapy users.
CONCLUSIONS: Our study provides evidence for a beneficial role of the Mediterranean diet on endometrial cancer risk, suggesting a favourable effect of a combination of foods rich in antioxidants, fibres, phytochemicals, and unsaturated fatty acids.

Rauh-Hain JA, Hariton E, Clemmer J, et al.
Incidence and effects on mortality of venous thromboembolism in elderly women with endometrial cancer.
Obstet Gynecol. 2015; 125(6):1362-70 [PubMed] Related Publications
OBJECTIVE: To describe the incidence of thromboembolic events (venous thromboembolism) before and after the diagnosis of epithelial endometrial cancer and to evaluate the effects of these events on survival.
METHODS: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registries linked to Medicare claim files to identify patients with epithelial endometrial cancer diagnosed between 1992 and 2009. To identify venous thromboembolism events 3 months before diagnosis and up to 24 months after diagnosis, we used International Classification of Diseases, 9th Revision, and Healthcare Common Procedure Coding System codes.
RESULTS: A total of 23,122 patients were included; of them 1,873 (8.1%) developed a venous thromboembolism. Patients with low-grade (grades 1 and 2) endometrioid adenocarcinoma had a significantly lower rate of venous thromboembolism 3 months before and 6 months after the diagnosis of cancer (3.6%; 95% confidence interval [CI] 3.3-3.9%) compared with carcinosarcoma (9.2%; 95% CI 7.8-10.8%), clear cell (6.9%; 95% CI 4.8-9.7%), uterine serous cancer (8.1%; 95% CI 7.01-9.3%), and grade 3 endometrioid adenocarcinoma (6.1%; 95% CI 5.4-6.9%) (P<.001). On multivariate analysis during the same time period, most recent time periods of diagnosis, carcinosarcoma histology compared with lower grade endometrial cancer, higher stage, African American race, marital status, chemotherapy delivery, and lymph node dissection were associated with increased risk of venous thromboembolism. The median overall survival for women who experienced a venous thromboembolism 3 months before the diagnosis of endometrial cancer was 31 months (95% CI 20-48 months); in women diagnosed with venous thromboembolism 6 months after the cancer diagnosis was 37 months (95% CI 31-44), and in women who did not experienced a venous thromboembolism was 111 months (95% CI 109-114). After adjusting for prognostic factors, there was an association between venous thromboembolism diagnosed 3 months before endometrial cancer (hazard ratio 1.69, 95% CI 1.34-2.13) or 6 months after the diagnosis (hazard ratio 1.57, 95% CI 1.44-1.71) and lower survival.
CONCLUSION: Patients with uterine serous cancer, carcinosarcoma, clear cell carcinoma, and grade 3 endometrioid adenocarcinoma had a higher rate of venous thromboembolism than patients with low-grade endometrioid adenocarcinoma. A diagnosis of venous thromboembolism was associated with decreased survival in elderly patients with endometrial cancer.

Li HM, Qiang JW, Xia GL, et al.
Primary ovarian endometrioid adenocarcinoma: magnetic resonance imaging findings including a preliminary observation on diffusion-weighted imaging.
J Comput Assist Tomogr. 2015 May-Jun; 39(3):401-5 [PubMed] Related Publications
OBJECTIVE: This study aimed to investigate the magnetic resonance imaging (MRI) features of ovarian endometrioid adenocarcinoma (OEC) and to evaluate conventional MRI and diffusion-weighted imaging (DWI) for diagnosing OEC.
MATERIALS AND METHODS: Twenty patients with OEC proven by surgery and pathology underwent MRI. The MRI features of the tumors evaluated included laterality, shape, size, configuration, mural nodules, signal intensity, apparent diffusion coefficient (ADC) values, enhancement, peritoneal implants, ascites, and synchronous primary cancer (SPC) of the ovary and endometrium.
RESULTS: Unilateral ovarian masses were observed in 18 (90%) of the 20 patients with 22 OEC lesions, whereas the remaining 2 (10%) patients had bilateral masses. Oval, lobulated, and irregular shapes were observed in 13 (59%), 6 (27%), and 3 (14%) tumors, respectively. The maximum diameter of the tumors ranged from 3.7 to 22.5 cm, with a mean of 11.2 ± 5.1 cm. Fifteen (68%) masses were mainly cystic with mural nodules, 5 (23%) were mixed cystic-solid, and 2 (9%) were solid. The solid components of tumors showed isointensity (100%) on T1-weighted imaging (T1WI), heterogeneous hyperintensity on T2-weighted imaging (T2WI) (86%), and hyperintensity on DWI (82%), with a mean ADC value of (0.96 ± 0.20) × 10 mm/s. The cystic components showed isointensity or hyperintensity (85%) on T1WI, hyperintensity on T2WI (100%), and hypointensity on DWI (63%), with a mean ADC value of (2.27 ± 0.27) × 10 mm/s. Ten (50%) of the patients were SPC. The mean ADC values of the solid components were (0.85 ± 0.19) × 10 mm/s and (1.08 ± 0.15) × 10 mm/s in only-OEC and SPC, respectively, with a statistically significant difference (P = 0.012).
CONCLUSIONS: Ovarian endometrioid adenocarcinoma usually appears as a large, oval, or lobulated cystic mass with mural nodules. Cystic components show isointensity or hyperintensity on T1WI, solid components and hyperintensity on T2WI and DWI. Synchronous primary cancer of the ovary endometrium is another characteristic feature of OEC.

Cărăuleanu A, Lupaşcu IA, Cărăuleanu DM, et al.
Clinico-epidemiological study of endometrial hyperplasia--a risk factor for the development of endometrial carcinoma?
Rev Med Chir Soc Med Nat Iasi. 2015 Jan-Mar; 119(1):154-61 [PubMed] Related Publications
AIM: Metaplasia is defined as a transformation of an adult epithelial or conjunctive cellular type into another adult cellular type. Endometrial hyperplasia and particularly complex atypical hyperplasia exposes to a high risk of development of the endometrial carcinoma, being considered a lesion precursory to the same. Endometrial hyperplasias are risk factors for the development of endometrial carcinoma and their prophylaxis implies their accurate diagnosis, taking into account that the adenocarcinomas diagnosed in an advanced stage, whose therapeutic context differs from the early stages, have a much lower chance of survival.
MATERIAL AND METHODS: Our study aimed at highlighting objective criteria in establishing the morphological diagnosis and in evaluating the prognostic elements. The studied batch included 875 patients with endometrial hyperplasia and 263 patients with endometrial adenocarcinoma, who were admitted between 2003 and 2007, and the histopathologic diagnosis was obtained by processing the hysterectomy pieces. The presence of this tumour was at its highest level half-way through the study, which was in 2005.
RESULTS: According to the study, there was a higher proportion of patients with endometrial carcinoma from the urban environment (58.2%) than the ones from the rural environment (only 41.8%). Depending on their age, most cases of endometrial adenocarcinoma were diagnosed in 53-year old patients, with an average age of 58.94 years. Our study, made of the two batches of endometrial adenocarcinomas, shows that between the endometrial and non-endometrial adenocarcinoma there are significant differences related to the patients' age, the morphological aspect of the carcinoma, the architectural degree, the nuclear degree of tumours and the invasion in the myometrium.
CONCLUSIONS: Our study proves that endometrial hyperplasia is a frequent diagnosis in peri- and postmenopausal patients and is frequently identified following investigations for an abnormal uterine bleeding. The age of patients with endometrial carcinoma is an important prognostic factor independent of other parameters. The difference between complex hyperplasia with no atypias and complex hyperplasia with atypias is important, because atypical complex hyperplasia is considered the precursor of endometrial adenocarcinoma.

The American College of Obstetricians and Gynecologists Committee Opinion no. 631. Endometrial intraepithelial neoplasia.
Obstet Gynecol. 2015; 125(5):1272-8 [PubMed] Related Publications
Endometrial hyperplasia is of clinical significance because it is often a precursor lesion to adenocarcinoma of the endometrium. Making the distinction between hyperplasia and true precancerous lesions or true neoplasia has significant clinical effect because their differing cancer risks must be matched with an appropriate intervention to avoid undertreatment or overtreatment. Pathologic diagnosis of premalignant lesions should use criteria and terminology that clearly distinguish between clinicopathologic entities that are managed differently. At present, the endometrial intraepithelial neoplasia schema is tailored most closely to this objective, incorporating modified pathologic criteria based upon evidence that has become available since the creation of the more widely used 1994 four-class World Health Organization schema (in which atypical hyperplasia is equated with precancerous behavior). The accuracy of dilation and curettage compared with endometrial suction curette in diagnosing precancer and excluding concurrent carcinoma is unclear. Hysteroscopy with directed biopsy is more sensitive than dilation and curettage in the diagnosis of uterine lesions. When clinically appropriate, total hysterectomy for endometrial intraepithelial neoplasia provides definitive assessment of a possible concurrent carcinoma and effectively treats premalignant lesions. Systemic or local progestin therapy is an unproven but commonly used alternative to hysterectomy that may be appropriate for women who are poor surgical candidates or who desire to retain fertility.

Jagielski L, Jelen M, Kobierzycki C, et al.
Increase of nuclear expression of metallothionein I/II in neoplastic transformation of the endomnetrium.
Ginekol Pol. 2015; 86(3):182-7 [PubMed] Related Publications
OBJECTIVES: The aim of our study was to investigate the expression of epidermal growth factor receptor (EGFR), metallothionein (MT) 1/11, and Ki-67 antigen in endometrial cancer We analyzed cytoplasmic (cMT) and nuclear (nMT) metallothionein fractions separately Moreover we evaluated the relationships between expressions of the above mentioned proteins and compared them with clinicopathologic data.
MATERIAL AND METHODS: The study material included paraffin-embedded endometrial cancer samples from 84 patients. The control group consisted of 52 non-neoplastic endometrium samples. Immunohistochemical reactions were performed using monoclonal antibodies against EGFR, MT 1/11 and Ki-67. Expression intensity of the tested proteins was assessed by computer image analysis software. Chi-square, Spearman's correlation, Mann-Whitney and Kruskal-Wallis tests were used for statistical analysis with Statistica 8.0 PL.
RESULTS: Strong expression of nMT was revealed in endometrial cancer cells in relation to benign hyperplasia (p<0.0017) and normal cells (p<0.001) of the endometrium. Statistically significant but weaker expressions in analogous relationships were observed for cMT Moreover higher grade of histological malignancy G was positively associated with increased expression of nMT (p=0.009).
CONCLUSIONS: Expression of nMT remains in distinct correlation with neoplastic transformation of the endometrium and histologic grades. Our results clearly indicate a need for further research on metallothionein expression in tumor cells.

Gao H, Zhang Z
Sequential chemotherapy and radiotherapy in the sandwich method for advanced endometrial cancer: a meta-analysis.
Medicine (Baltimore). 2015; 94(16):e672 [PubMed] Related Publications
Endometrial cancer is one of the most common gynecological malignancies and the standard treatment modality has not been established.To assess the efficacy and tolerability of a sandwich method consisted of chemotherapy followed by involved field irradiation and additional chemotherapy for the treatment of advanced endometrial cancer.The Medline, Embase, Cochrane, and China National Knowledge Infrastructure (CNKI) Library were searched to identify the relevant literature published between 1970 and September 2014. A meta-analysis was performed to evaluate progression-free survival (PFS), overall survival (OS), and toxicity.A total of 5 articles were subjected to this meta-analysis. The pooled 3-year PFS and OS of patients with advanced endometrial cancer treated with the "sandwich" method was 68% (95% CI: 0.60-0.77) with no heterogeneity (I = 0.00%, P = 0.77) among the studies and 75% (95% CI: 0.61-0.89) with significant heterogeneity (I = 71.8%, P = 0.01), respectively. Pooled analysis of toxicity was not performed because of the substantial heterogeneity.Sequential chemotherapy and radiotherapy in the sandwich method is both efficacious and well tolerated. Large-scale randomized controlled trials (RCTs) are necessary in the future.

Reynaers EA, Ezendam NP, Pijnenborg JM
Comparable outcome between endometrioid and non-endometrioid tumors in patients with early-stage high-grade endometrial cancer.
J Surg Oncol. 2015; 111(6):790-4 [PubMed] Related Publications
BACKGROUND: Approximately 25% of endometrial cancer patients present with high-grade tumors. Unlike the clearly defined work-up for non-endometrioid endometrial cancer, no consensus exists for surgical staging and adjuvant therapy in high-grade endometrioid endometrial cancer. We compared the recurrence rate and disease-related mortality (DRM) after treatment between endometrioid and non-endometrioid endometrial cancer.
METHODS: A total of 123 patients diagnosed with early-stage high-grade endometrial cancer at the Dutch Comprehensive Cancer Centre South (CCCS) between January 2005 and December 2011 were included. All patients underwent abdominal hysterectomy and bilateral salpingo-oophorectomy. Patient and tumor characteristics, primary and adjuvant treatment, and outcome were analyzed.
RESULTS: After a median follow-up of 27.9 months, 27.6% (n = 34) of patients had recurrent disease. Distant recurrence rate was equal among endometrioid (14.5%), papillary serous (14.8%), and clear cell (15.4%) types. The total DRM was 15.4% (n = 19). The 5 year recurrence-free survival was not significantly different between early-stage high-grade endometrioid versus non-endometrioid endometrial cancer (P = 0.72).
CONCLUSION: Distant recurrence and DRM was high in patients with endometrial cancer regardless of histological type, suggesting the need for different therapies in early-stage high-grade non-endometrioid and endometrioid tumors.

Frey MK, Lin JF, Stewart LE, et al.
Comparison of two minimally invasive approaches to endometrial cancer staging: a single-surgeon experience.
J Reprod Med. 2015 Mar-Apr; 60(3-4):127-34 [PubMed] Related Publications
OBJECTIVE: To compare the clinical outcomes of endometrial cancer staging procedures performed by a single surgeon utilizing traditional and robotic-assisted laparoscopic techniques.
STUDY DESIGN: A retrospective review of minimally invasive endometrial cancer staging performed by a single surgeon.
RESULTS: There were no significant differences in operative time, blood loss, surgical complications, or length of hospitalization between laparoscopic (n = 45) and robotic-assisted (n = 77) procedures. On multivariable analysis controlling for surgical chronology, robotic assistance was independently associated with a significantly greater number of lymph nodes (23 vs. 19, p < 0.05; beta 0.163, p < 0.05). When comparing the first chronologic half of robotic-assisted surgeries to the second half, the latter had shorter operative time (208 vs. 246 min, p = 0.01) and a greater number of lymph nodes (27 vs. 19, p = 0.001). Finally, compared to the laparoscopic cases, the second half of robotic-assisted cases had a greater number of total (27 vs. 19, p < 0.001) and pelvic (23 vs. 17, p < 0.001) lymph nodes harvested.
CONCLUSION: There was a learning curve associated with robotic-assisted laparoscopic endometrial cancer staging, with decreased operative time and increased lymph node yield over time. In our study population, robotic assistance was independently associated with a greater lymph node harvest with no increase in operative time or perioperative complications.

Androutsopoulos G, Adonakis G, Terzakis E, et al.
Endometrial cancer in a patient with rheumatoid arthritis.
Eur J Gynaecol Oncol. 2015; 36(1):91-3 [PubMed] Related Publications
BACKGROUND: Rheumatoid arthritis is a chronic, systemic, and autoimmune disease. In patients with rheumatoid arthritis, there is increased risk for site-specific malignancies. The authors present a case of endometrial cancer in a patient with rheumatoid arthritis and a review of the current literature.
CASE: The patient, a 60-year-old, postmenopausal Greek woman suffering from rheumatoid arthritis, presented with a complaint of abnormal uterine bleeding. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy. Histopathology revealed endometrial cancer. The final diagnosis was Stage Ib endometrial cancer endometrioid type. She underwent postoperative adjuvant radiotherapy. She remains without evidence of disease, 16 months after initial surgery.
CONCLUSION: Although the present patient was diagnosed at early-stage disease and remains well 16 months after initial surgery, she needs a multidisciplinary treatment approach in order to achieve prolonged survival.

Kerimoglu OS, Pekin A, Yilmaz SA, et al.
Pyometra in elderly post-menopausal women: a sign of malignity.
Eur J Gynaecol Oncol. 2015; 36(1):59-61 [PubMed] Related Publications
PURPOSE: To describe the clinical and histopathological characteristics of 12 patients with pyometra and highlight the increased incidence of gynecological malignancy in these patients.
MATERIALS AND METHODS: The authors examined the medical records of 12 patients with pyometra, who were treated between 2009 and 2013.
RESULTS: All patients were post-menopausal, and their mean age was 70.83 ± 6.978 years (min = 61, max = 82). To remove purulent fluid via dilation and because of the probability of malignancy, three patients (25%) underwent cervical biopsy and endometrial curettage; the other nine patients (75%) underwent curettage alone, with suitable antibiotic therapy. Of the 12 patients, nine (75%) had gynecologic malignancy [(endometrial cancer, n = 5, 41.6%), (cervical cancer, n = 3, 25%), (uterine leiomyosarcoma, n = 1, 8.3%)]. In three (25%) patients, the cause of pyometra was benign pathologies, among which the most common were leiomyomas (n = 2, 66.6%).
CONCLUSION: Pyometra diagnosed during the post-menopausal period should be considered a complication caused by gynecological malignancy until proven otherwise.

Xiao YT, Luo LM, Zhang R
Effect of lentivirus mediated cyclooxygenase-2 gene shorthairpinRNA on invasiveness of endometrial carcinoma.
Eur J Gynaecol Oncol. 2015; 36(1):44-8 [PubMed] Related Publications
OBJECTIVE: This study aims to explore the effects of lentivirus mediated cyclooxygenase-2 gene shorthairpinRNA (COX-2-shRNA) on invasiveness of endometrial carcinoma HEC-1B cells.
MATERIALS AND METHODS: Double-stranded DNA oligonucleotide of COX-2-shRNA was designed and synthesized, and the recombinant lentiviral vector COX-2-ShRNA (LV-COX-2-ShRNA) was constructed. LV-COX-2-ShRNA, pHelper 1, and pHelper 2 were transferred into 293T cells, followed by lentiviral packaging. The virus titer was tested according to expression level of GFP in 293T cells. HEC-1B cells were infected with recombinant lentivirus. The silencing of COX-2 gene was assessed by real-time PCR and western-blot, and the in vivo invasiveness of HEC-1B cells was analyzed by transwell invasion assay.
RESULTS: Recombinant lentiviral vector expressing siRNA targeting COX-2 gene was successfully constructed to harvest the recombinant lentivirus with the concentrated virus suspension titer of 5 x 10(7)Tu/ml. Compared with control group, the inhibitory rate of COX-2 expression in HEC-1B cells in siRNA group were 61.87% and 67.48% at mRNA and protein level, respectively. The mean number of cells penetrating matrigel was 16.6, which was significantly less than the control group 50.2 and non-specific siRNA infection group 47.2, the invasion inhibition rate being 64.8% (p < 0.01).
CONCLUSION: RNA interference can inhibit the invasiveness of HEC-in cells.

Machado-Linde F, Sánchez-Ferrer ML, Cascales P, et al.
Prevalence of endometriosis in epithelial ovarian cancer. Analysis of the associated clinical features and study on molecular mechanisms involved in the possible causality.
Eur J Gynaecol Oncol. 2015; 36(1):21-4 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: To determine the prevalence of endometriosis in patients with epithelial ovarian cancer and explore the differences between women with endometrioid and clear-cell histologic subtypes with and without associated endometriosis.
MATERIALS AND METHODS: The medical charts of 496 patients with epithelial ovarian cancer at the Hospital Virgin de la Arrixaca (Murcia, Spain) between 1971 and 2010 were reviewed.
RESULTS: Endometriosis was present in 27 (5.4%) of the 496 cases (p < 0001), and was associated with the endometrioid histotype in 13/45 cases (29%) and with the clear cell histotype in 7/22 (32%). The prevalence of an association with endometriosis according to histologic type was 28.8% (13/45) for endometrioid carcinoma and 31.8% (7/22) for clear-cell carcinoma.
CONCLUSION: Both endometrioid and clear-cell ovarians tumours are associated with pelvic endometriosis. Patients with endometiosis associated ovarian cancer differ from non-endometiosis associated ovarian cancer in their clinical characteristics.

Mizuno M, Kajiyama H, Shibata K, et al.
Prognostic value of histological type in stage IV ovarian carcinoma: a retrospective analysis of 223 patients.
Br J Cancer. 2015; 112(8):1376-83 [PubMed] Article available free on PMC after 14/04/2016 Related Publications
BACKGROUND: Patients with FIGO stage IV epithelial ovarian carcinoma have a poor but non-uniform prognosis. This study aimed to compare the survival of patients with serous or endometrioid tumours (S/E) and clear cell or mucinous tumours (non-S/E).
METHODS: Data for 223 patients who underwent surgery between 1987 and 2010 and were diagnosed by centralized pathology review and were retrospectively analysed. The patients included 169 with S/E tumours and 54 with non-S/E tumours.
RESULTS: The median overall survivals (OSs) of the S/E and non-S/E groups were 3.1 and 0.9 years, respectively (P<0.001). Six patients (2.7%), all with non-S/E tumours, died within 6 weeks after the initial surgery. Multivariate OS analysis revealed that performance status, residual tumor, metastatic sites, no debulking surgery, and non-S/E tumours were independent poor prognostic factors. For patients with non-S/E tumours, prognosis was more favourable for single-organ metastasis, except for liver or distant lymph nodes, no residual tumor, and resection of metastasis (median OS: 4.1, 4.6, and 2.6 years, respectively).
CONCLUSIONS: In stage IV ovarian carcinoma, non-S/E tumours are associated with a significantly poorer prognosis and higher rates of early mortality compared to S/E tumours. Therefore, careful management and development of new strategies are required.

Abid N, Kallel R, Mellouli M, et al.
Mixed stromal and smooth muscle tumours of the uterus: a report of two cases.
Pathologica. 2014; 106(4):330-4 [PubMed] Related Publications
Mixed stromal and smooth muscle uterine tumours, defined as those containing at least 30% of each component as seen by routine light microscopy, are rare. This report describes the morphological features of two such tumours diagnosed in 44-year-old and 50-year-old females complaining from recurrent uterine bleeding that was unresponsive to medical treatment. Morphological and immunohistochemical evaluations were performed, and a final diagnosis of mixed endometrial stromal nodule and smooth muscle tumour of the uterus was rendered in both cases.

Shawana S, Kehar SI, Shaikh F
Differential expression of phophatase and tensin homologue in normal, hyperplastic and neoplastic endometrium.
J Pak Med Assoc. 2014; 64(10):1103-8 [PubMed] Related Publications
OBJECTIVES: To observe the differential expression of phophatase and tensin homologue in normal proliferative, hyperplastic and malignant endometrial lesions.
METHODS: .The retrospective study was based on the analysis of endometrial samples, both hysterectomies and curettage, received at the department of pathology Basic Medical Sciences Institute at the Jinnah Postgraduate Medical Centre, Karachi, from January 1, 2006 to December 31, 2010. A total of 55 endometrial samples were analysed for morphological features and results of immunohistochemical staining.
RESULTS: Of the 55 samples, 25 (45.45%) were malignant endometrial lesions, 6 (10.9%) complex hyperplasias with atypia, 14(25.45%) complex hyperplasias without atypia hyperplasia, 6 (10.9%) simple hyperplasias without atypia, and 4 (7.27%) normal proliferative endometrium. Among malignant endometrial lesions, 12 (48%) showed complete loss of phophotase and tensin homologue expression out of which majority were endometroid adenocarcinoma. Five (83.3%) cases of complex hyperplasias with atypia and 9 (64.28%) cases of complex hyperplasia without atypia showed complete loss of or diminished expression of phophotase and tensin homologue.
CONCLUSION: Loss of phophotase and tensin homologue expression was seen in a significant number of well differentiated endometrial adenocarcinomas and complex hyperplasias with atypia suggesting loss of PTEN expression as an early event in endometrial carcinogenesis.

Mojakgomo R, Mbita Z, Dlamini Z
Linking the ceramide synthases (CerSs) 4 and 5 with apoptosis, endometrial and colon cancers.
Exp Mol Pathol. 2015; 98(3):585-92 [PubMed] Related Publications
Ceramide synthases (CerSs) also known as Longevity Assurance (LASS) genes belong to a family of six related genes. CerS gene products have been shown to produce ceramide, hence their name CerSs. Ceramide is a bio-effector molecule, belonging to the family of sphingolipids (SLs), which are important components of cell membranes, and has been implicated in cancer and apoptosis. Cancer still remains the second leading cause of death, both globally and in South Africa. The proper regulation of the balance between cell growth and cell death is essential for cellular homeostasis. Failure to properly regulate this balance may lead to pathologic conditions such as cancer development. CerSs have been implicated in cancer biology, especially in apoptosis, through the action of ceramide. Although knowledge of the role that CerSs play in cancer biology is advancing, the precise roles of distinct CerSs in different cancers are not yet fully understood, especially the roles of CerS4 and CerS5 in endometrial and colon cancers. The aim of this study was to investigate the link of CerS4 and CerS5 in apoptosis and, thus in cancers of the endometrium and colon, which are amongst the most prevalent cancers globally. Apoptosis was induced using anastrozole in endometrial cells and 5-FU in colon cells. Fluorescence activated cell sorting was used to analyse and quantify apoptosis and total RNA was extracted from both treated and untreated cells. Quantitative relative expression of CerS4 and CerS5 mRNA was then determined in all cells (treated and untreated), normalised to β-actin. Bio-informatics was used to compare CerS4 and CerS5 sequences. The endometrial cancer cells were more prone to apoptosis compared to their non-cancerous counterparts, while the colon cancer cells were more responsive to apoptosis induction after 48h, especially the HT-29 cells. Using quantitative real-time PCR, both CerS4 and CerS5 were shown to be up-regulated in endometrial and colon cancer cells. Apoptosis induction resulted in down-regulation of CerS4 and CerS5 in endometrial and colon cancers. These findings implicate these genes in cancer and apoptosis. Whether these genes play pro- or anti-apoptotic roles in cancers of the endometrium and colon is not conclusive at this stage. It may also be possible that these genes could exert opposing roles in the same or different tissues. Targeting this family of genes and understanding their precise individual roles in different types of cancer, are a promising therapeutic tool to new anti-cancer drug discovery or improving existing treatments.

Celik B, Didem Yalcin A, Esra Genc G, Gumuslu S
Proteomics pattern of peritoneal sApo-2L but not CD200 (OX-2) as a possible screening biomarker for metastatic ovarian, endometrial and breast carcinoma.
J BUON. 2015 Jan-Feb; 20(1):280-6 [PubMed] Related Publications
PURPOSE: The purpose of this study was to evaluate the soluble Apo-2L (sApo-2L) levels in the ascitic fluid and to study its potential in detecting malignant ascites and soluble CD200 (sCD200,sOX-2) levels so as to predict its clinical usage for detecting stage 4 metastatic endometrial, ovarian and breast cancer in serum samples.
METHODS: Ascitic fluid from 53 and blood from 25 subjects without known malignancy on admission were collected. There were 14 breast cancer (BC), 17 ovarian cancer (OC) and 19 endometrial cancer (EC) patients diagnosed later on. Blood samples for sApo-2L, sCD200, liver function tests and CEA, CA-19.9 and CA-125 were always taken and assayed in the morning.
RESULTS: Significantly low levels of sApo-2L were observed in peritoneal fluid from OC and EC patients compared to benign peritoneal fluid from control individuals. Positive correlation was observed between sApo-2L and aspartate aminotransferase (AST) in benign peritoneal fluid and sCD200, and creatinine and sCD200 and platelets in OC patients; also, sCD200 and CEA in EC patients and sCD200 and blood urea nitrogen (BUN) in healthy subjects.
CONCLUSIONS: Our data indicate that low proteomics pattern of sApo-2L but not sCD200 is a good biochemical marker. Further decline in the level of sApo-2L was seen in EC compared to OC. Since higher levels of sApo-2L were seen with higher levels of AST, the liver might be involved in its metabolism. The positive correlation detected between sCD200 and creatinine, platelets, CEA and BUN needs to be elucidated.

Flicker K, Smolle E, Haybaeck J, Moinfar F
Genomic characterization of endometrial stromal sarcomas with array comparative genomic hybridization.
Exp Mol Pathol. 2015; 98(3):367-74 [PubMed] Related Publications
INTRODUCTION: The endometrial stromal sarcoma (ESS) is a very rare uterine sarcoma, counting for 1-3% of all gynecologic malignancies. ESS represents 0.2-8% of all uterine malignant tumors and accounts for about 10% of all uterine sarcomas. With regard to chromosomal aberrations, very little is known about benign and malignant endometrial stromal tumors.
METHODS: 30 tumors, consisting of 4 cases of benign endometrial stromal nodule (ESN), 22 cases of low-grade ESS and 4 cases of undifferentiated endometrial sarcoma (UES), were analyzed by array-comparative genomic hybridization (aCGH).
RESULTS: ESN did not show many copy number changes (CNCs) by aCGH. Frequent losses could be identified on chromosomes 7p and 19, and gains on chromosomes 1q, 6p and 8q. Low-grade ESS presented as a very heterogeneous group. 90% (20/22) of cases displayed aberrations. Most frequent changes were losses on chromosomes 7 and 22, and gains on chromosome 1q or 11. UES showed a high number of chromosomal aberrations and on every chromosome CNCs were detected. Most frequent changes were losses on chromosomes 1q, 2q (3/4, 75%) and 13, and gains on chromosomes 1q and 17p.
CONCLUSION: Our data shows an increasing number of CNCs from ESN to low-grade ESS and to UES. However, the chromosomal aberrations differ considerably between the investigated ESN-, low-grade ESS- and UES cases and thus, a linear tumor progression seems to be unlikely.

Rauh-Hain JA, Buskwofie A, Clemmer J, et al.
Racial disparities in treatment of high-grade endometrial cancer in the Medicare population.
Obstet Gynecol. 2015; 125(4):843-51 [PubMed] Related Publications
OBJECTIVE: To examine the patterns of care and survival for African American and white women with high-grade endometrial cancer.
METHODS: The linked Surveillance, Epidemiology, and End Results and Medicare databases were queried to identify patients diagnosed with grade 3 endometrioid endometrial adenocarcinoma, uterine carcinosarcoma, uterine clear cell carcinoma, and uterine serous carcinoma between 1992 and 2009. The effect of treatment modality on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model.
RESULTS: A total of 9,042 patients met study eligibility criteria. African Americans had definitive surgery (76.8% compared with 88.7%; P<.001) less frequently. There was no difference in the rate of adjuvant treatment between the groups. In the crude models for both all-cause mortality and cancer-specific mortality, African American women had an increased overall and disease-specific hazard of death compared with white women. The overall hazard ratio for African American women was 1.6 (95% confidence interval [CI] 1.5-1.7), and the disease-specific hazard ratio was 1.5 (95% CI 1.3-1.6). Over the entire study period, after adjusting for stage, age, period of diagnosis, registry region, urban compared with rural setting, marital status, treatment, surgery, socioeconomic status, and comorbidities, there was no association between race and lower disease-specific survival (hazard ratio 1.1, 95% CI 1-1.2; P=.06).
CONCLUSION: African American women had lower cancer-specific and all-cause survival compared with white women. Controlling for treatment, sociodemographics, comorbidities, and histopathologic variables eliminated the difference between African American and white women in the disease-specific analysis.

Yoneyama K, Ishibashi O, Kawase R, et al.
miR-200a, miR-200b and miR-429 are onco-miRs that target the PTEN gene in endometrioid endometrial carcinoma.
Anticancer Res. 2015; 35(3):1401-10 [PubMed] Related Publications
Endometrioid endometrial carcinoma (EEC) is a common malignancy of the female genital tract. However, no adequate biomarker is currently available for predicting the prognosis of this cancer. Recent studies have revealed dysregulated expression of several microRNAs (miRNAs) in various cancer tissues, and therefore, these cancer-associated miRNAs (also called onco-miRs) could be promising prognostic biomarkers of cancer progression or metastasis. In this study, in order to identify onco-miRs and their possible targets involved in EEC, we performed microarray-based integrative analyses of miRNA and mRNA expression in specimens excised from EEC lesions and adjacent normal endometrial tissues. Using integrated statistical analyses, we identified miR-200a, miR-200b and miR-429 as highly up-regulated onco-miRs in EECs. Conversely, we detected expression of a tumor-suppressor gene, phosphatase and tensin homolog (PTEN), which was predicted in silico using a miRNA-targeting mRNA prediction algorithm, as a target of the three miRNAs and which was down-regulated in EECs. Furthermore, these miRNAs were validated to target PTEN experimentally using luciferase assays and real-time polymerase chain reaction. These results suggest that the occurrence of EEC is, at least in part, mediated by miRNA-induced suppression of PTEN expression.

Brasky TM, Rodabough RJ, Liu J, et al.
Long-chain ω-3 fatty acid intake and endometrial cancer risk in the Women's Health Initiative.
Am J Clin Nutr. 2015; 101(4):824-34 [PubMed] Article available free on PMC after 01/04/2016 Related Publications
BACKGROUND: Inflammation may be important in endometrial cancer development. Long-chain ω-3 (n-3) polyunsaturated fatty acids (LCω-3PUFAs) may reduce inflammation and, therefore, reduce cancer risk. Because body mass is associated with both inflammation and endometrial cancer risk, it may modify the association of fat intake on risk.
OBJECTIVE: We examined whether intakes of LCω-3PUFAs were associated with endometrial cancer risk overall and stratified by body size and histologic subtype.
DESIGN: Women were n = 87,360 participants of the Women's Health Initiative Observational Study and Clinical Trials who were aged 50-79 y, had an intact uterus, and completed a baseline food-frequency questionnaire. After 13 y of follow-up, n = 1253 incident invasive endometrial cancers were identified. Cox regression models were used to estimate HRs and 95% CIs for the association of intakes of individual ω-3 fatty acids and fish with endometrial cancer risk.
RESULTS: Intakes of individual LCω-3PUFAs were associated with 15-23% linear reductions in endometrial cancer risk. In women with body mass index (BMI; in kg/m(2)) <25, those in the upper compared with lowest quintiles of total LCω-3PUFA intake (sum of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) had significantly reduced endometrial cancer risk (HR: 0.59; 95% CI: 0.40, 0.82; P-trend = 0.001), whereas there was little evidence of an association in overweight or obese women. The reduction in risk observed in normal-weight women was further specific to type I cancers.
CONCLUSIONS: Long-chain ω-3 intake was associated with reduced endometrial cancer risk only in normal-weight women. Additional studies that use biomarkers of ω-3 intake are needed to more accurately estimate their effects on endometrial cancer risk. This trial was registered at clinicaltrials.gov as NCT00000611.

Yang TO, Crowe F, Cairns BJ, et al.
Tea and coffee and risk of endometrial cancer: cohort study and meta-analysis.
Am J Clin Nutr. 2015; 101(3):570-8 [PubMed] Article available free on PMC after 01/04/2016 Related Publications
BACKGROUND: Previous reports, mostly from retrospective studies, suggested possible protective effects of both tea and coffee against endometrial cancer, but recent reports from prospective studies generally showed weaker or null associations.
OBJECTIVES: We investigated endometrial cancer risk in relation to tea and coffee consumption in a large prospective study and did a meta-analysis of published results.
DESIGN: Daily consumption of tea and coffee was recorded in 560,356 participants (without a hysterectomy) in the UK Million Women Study of whom 4067 women developed endometrial cancer during 5.2 million person-years of follow up (average: 9.3 y per woman).
RESULTS: With the use of Cox proportional hazards regression, we showed no significant association between endometrial cancer risk and consumption of either tea (multivariate adjusted RR per cup daily: 1.00; 95% CI: 0.98, 1.02) or coffee (RR per cup daily: 0.98; 95% CI: 0.96, 1.01). Our meta-analyses showed no significant association between endometrial cancer risk and tea consumption and a weak association for coffee consumption in prospective studies, but there may have been selective publication of only part of the evidence.
CONCLUSIONS: There is little or no association between tea consumption and endometrial cancer risk. If there is any association with coffee consumption, it appears to be weak.

Saleh FM, Ansari NP, Eunus MF, Mirza TT
Endometrial stromal nodule - a case report.
Mymensingh Med J. 2015; 24(1):178-81 [PubMed] Related Publications
Among the endometrial tumour endometrial stromal nodule are very rare. It is one of the form of endometrial stromal tumour. There are no definite presurgical diagnosis and diagnosis in most instances by microscopy. Hysterectomy is the treatment of choice to evaluate the tumour margin to differentiate it from stromal sarcoma. We present a case of 40 years woman, ultrasonographically diagnosed as leiomyoma and ovarian cystadenoma, underwent a total abdominal hysterectomy with one sided salpingo-oophorectomy. Microscopic examination show an endometrial stromal nodule and serous cystadenoma of the ovary. Though it is a benign tumour margin should be carefully examined to differentiate from stromal sarcoma, whose treatment and prognosis is totally different.

Dong R, Pu H, Wang Y, et al.
TESTIN was commonly hypermethylated and involved in the epithelial-mesenchymal transition of endometrial cancer.
APMIS. 2015; 123(5):394-400 [PubMed] Related Publications
We previously reported frequent loss of TESTIN in human endometrial carcinoma, which significantly suppressed tumor proliferation and invasion. Herein, we further explored the mechanisms underlying TESTIN loss and its roles in the epithelial-mesenchymal transition (EMT, a key step for tumor spreading). Methylation-specific PCR was performed to investigate the promoter status of TESTIN in a panel of endometrial cancer and normal endometrium tissues. The expression of TESTIN mRNA was determined by real-time PCR. Up- and down-regulation of TESTIN were achieved by transient transfection with pcDNA3.1-TESTIN and shRNA-TESTIN plasmids, respectively. The EMT alterations were observed under the optical microscope and EMT-related markers were detected by real-time PCR and western blot. Compared to the control (3.6%), TESTIN was hypermethylated in 43.7% endometrial cancer tissues (p < 0.001). Moreover, TESTIN hypermethylation was significantly correlated with advanced tumor stage, deep myometrial invasion and lymphatic node metastasis. In vitro, the demethylating agent dramatically restored the expression of TESTIN. In addition, up-regulation of TESTIN significantly suppressed the EMT procedure; whereas down-regulation of TESTIN enhanced EMT. In conclusion, we demonstrated that loss of TESTIN was mainly caused by hypermethylation, which might be a potent prognostic marker. Furthermore, we proved that TESTIN significantly suppressed the EMT procedure, proposing restoration of TESTIN to be a novel therapeutic strategy for endometrial carcinoma.

Newcomb PA, Passarelli MN, Phipps AI, et al.
Oral bisphosphonate use and risk of postmenopausal endometrial cancer.
J Clin Oncol. 2015; 33(10):1186-90 [PubMed] Article available free on PMC after 01/04/2016 Related Publications
PURPOSE: Bisphosphonates are common medications used for the treatment of osteoporosis and are also used to reduce metastases to bone in patients with cancer. Several studies, including the Women's Health Initiative (WHI), have found that use of bisphosphonates is associated with reduced risk of developing breast cancer, but less is known about associations with other common malignancies. This study was aimed at examining the effects of bisphosphonates on the risk of endometrial cancer.
METHODS: We evaluated the relationship between use of oral bisphosphonates and endometrial cancer risk in a cohort of 89,918 postmenopausal women participating in the WHI. A detailed health interview was conducted at baseline, and bisphosphonate use was ascertained from an inventory of regularly used medications at baseline and over follow-up. All women had an intact uterus at the time of study entry.
RESULTS: During a median follow-up of 12.5 years, 1,123 women were diagnosed with incident invasive endometrial cancer. Ever use of bisphosphonates was associated with reduced endometrial cancer risk (adjusted hazard ratio, 0.80; 95% CI, 0.64 to 1.00; P = .05), with no interactions observed with age, body mass index, or indication for use.
CONCLUSION: In this large prospective cohort of postmenopausal women, bisphosphonate use was associated with a statistically significant reduction in endometrial cancer risk.

Wang H, Bao W, Jiang F, et al.
Mutant p53 (p53-R248Q) functions as an oncogene in promoting endometrial cancer by up-regulating REGγ.
Cancer Lett. 2015; 360(2):269-79 [PubMed] Related Publications
P53 mutation plays a pivotal role in tumorigenesis of endometrial cancer (EC), here we report that the gain-of-function mutant p53-R248Q targets the proteasome activator REGγ to promote EC progression. Increased p53 expression significantly correlated with high pathological grade and lymph node metastasis in EC specimens. Manipulation of p53-R248Q in EC cells caused coincident changes in REGγ expression, and chromatin immunoprecipitation coupled with PCR further indicated that p53-R248Q bound to the REGγ gene promoter at a p53 responsive element. Silencing of REGγ in EC cells attenuated the cell proliferation, migration and invasion abilities, whereas overexpression of p53-R248Q rescued these activities. Overexpression of REGγ also induced an epithelial-mesenchymal transition phenotype. Moreover, a mouse xenograft tumor model showed that REGγ promoted tumor growth, further demonstrating a p53-R248Q-REGγ oncogenic pathway. Finally, examination of EC and normal endometrium specimens confirmed the oncogenic role of REGγ, in that REGγ was more highly overexpressed in p53-positive specimens than in p53-negative specimens. Our data suggest that REGγ is a promising therapeutic target for EC with the p53-R248Q mutation.

Yang HP, Cook LS, Weiderpass E, et al.
Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2).
Br J Cancer. 2015; 112(5):925-33 [PubMed] Article available free on PMC after 03/03/2016 Related Publications
BACKGROUND: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes.
METHODS: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).
RESULTS: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59-1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13-1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer.
CONCLUSIONS: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters.

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