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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Schmolze D, Awtrey CS, Hecht JL Value of additional level sections in the evaluation of lymph nodes for endometrial carcinoma staging. Am J Clin Pathol. 2013; 140(4):516-8 [PubMed] Related Publications
OBJECTIVES: To evaluate the value of deeper sections for conventional (non-sentinel) lymph node dissections in high-risk endometrial carcinoma (EC). METHODS: We conducted a retrospective review of all ECs with high-grade or serous histology, more than 50% myometrial invasion or International Federation of Gynecology and Obstetrics (FIGO) pathologic stage greater than 2, and conventional complete pelvic lymph node dissections. No sentinel lymph node (SLN) biopsies were performed. Nodes were originally processed entirely in 3-mm slices, with residual fatty tissue submitted separately. When lymph nodes were negative on original H&E sections, paraffin blocks were sectioned to produce 1 additional H&E slide at approximately 0.8 mm deep. With positive nodes, we examined the relationship between micrometastases, staging parameters, and recurrence. RESULTS: Fifty-one high-risk cases were identified, with a median of 15 pelvic lymph nodes per case. Fifteen (29%) cases contained positive nodes. Review of the original slides and additional sections of all blocks from the remaining 36 cases failed to reveal metastases. Statistically significant associations were found between node status and depth of myometrial invasion, lymphovascular invasion, and FIGO stage. We found no significant relationship between lymph node status and serous histology. CONCLUSIONS: Our results suggest that enhanced detection of metastasis by SLN biopsies may be related to targeted lymph node selection rather than additional histologic sectioning.
Kanda M, Sonoyama A, Hirano H, et al. Transition of low-grade to high-grade endometrial stromal sarcoma: a case report. Eur J Gynaecol Oncol. 2013; 34(4):358-61 [PubMed] Related Publications
BACKGROUND: The transition of low-grade endometrial stromal sarcoma (ESS) to high-grade ESS remains a rare clinical event. CASE: A patient presented with abdominal pain and abnormal genital bleeding. She underwent a supracervical hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and resection of peritoneal disseminated lesions. Pathological examination revealed low-grade ESS in the uterus and omentum. Immunohistochemical examination showed immunoreactivity for CD10 and Ki-67 (MIB1) in the uterus and omentum. However, estrogen receptor, progesterone receptor, alpha-SMA, desmin, h-caldesmon, and CAM5-2 were negative. P53 immunoreactivity was noted only in the omental lesion. Despite performing six courses of adjuvant chemotherapy, she recurred in the abdomen. She underwent ileostomy and resection of peritoneal disseminated lesions. Pathology showed high-grade ESS in the recurrent lesion of the ileum, which was characterized by severe cytologic atypia, high mitotic index, multifocal necrosis, increased Ki-67 index, and immunoreactivity for p53. CONCLUSION: Although rare, the transition of low-grade ESS to high-grade ESS may occur and suggests the worsening of the prognosis. Pathological examination and immunohistochemistry are useful for the diagnosis of the transition of low-grade ESS to high-grade ESS.
Li Y, Lu HJ, Yang Y Primary squamous cell carcinoma of endometrium: clinicopathologic analysis of two cases with review of the literature. Eur J Gynaecol Oncol. 2013; 34(4):355-7 [PubMed] Related Publications
Two cases of primary squamous cell carcinomas of the endometrium (PSCCE) are reported, and both were postmenopausal and presented with vaginal bleeding. Histologically, the endometrial curetting revealed extensive squamous metaplastic papillae with vacuolated cytoplasms. Numerous keratin debris were present in the superficial epithelium with neutrophils infiltration. Atypia existed in the basal and parabasal-layer cells. It can be regarded as precancerous lesion when postmenopausal woman's endometrial curetting show extensive squamous papillae.
Ma XG, Wang YM, Sheng HN, et al. Endometrial cancer metastasize to the skin of lower leg and vagina: case report and literature review. Eur J Gynaecol Oncol. 2013; 34(4):350-2 [PubMed] Related Publications
Endometrial cancer is the most frequent malignancy of the female reproductive system, while cutaneous metastasis is extremely rare in endometrial cancer. The authors herein report a case ofendometrial adenocarcinoma (FIGO Stage IIIC2, Grade 2) with metastasis to the skin of right lower leg and vaginal orifice. The patient was treated with local excision and combination chemotherapy, but she did not respond to therapy and died within 11 months. The authors reviewed the clinico-pathologic features, treatment, and prognosis of such case with cutaneous metastasis.
Chen CY, Huang KG, Abdullah NA, et al. Successful treatment of isolated fibular bone metastasis in a uterine endometrial cancer of clear cell carcinoma. Eur J Gynaecol Oncol. 2013; 34(4):347-9 [PubMed] Related Publications
Clear cell carcinoma of the endometrium is an uncommon histological subtype and isolated metastasis to bone is rare. The authors present a case of a 61-year-old woman who underwent laparoscopic staging surgery for clear cell carcinoma of uterine endometrium (FIGO Stage IB) and early recurrence with isolated fibular bone metastasis three months later. With salvage radiotherapy (RT), she remains disease-free after 46 months. Curative-intended treatment with RT is possible as in this case.
Matejcková J, Samec M, Samcová E, et al. The effect of vitamin E on plasmatic malondialdehyde levels during surgical removal of ovarian and endometrial carcinomas. Eur J Gynaecol Oncol. 2013; 34(4):329-31 [PubMed] Related Publications
This study deals with the monitoring of plasmatic levels of malondialdehyde, as the main indicator of oxidative damage to biomembranes. Malondialdehyde is determined by high-performance liquid chromatography (HPLC) after derivatization employing 2,4-dinitrophenylhydrazine. A clinical study involving 20 female patients suffering from ovarian and endometrial carcinomas has demonstrated elevated levels of malondialdehyde (10.1 +/- 1.1 microM), compared with the control group (7.5 +/- 2.7 microM). It has been further verified that surgical removal of the tumor leads to an additional increase in the plasmatic malondialdehyde content. This unfavourable situation can be effectively eliminated by administration of a single dose of vitamin E prior to surgery.
Ozdal B, Unlu BS, Yalcin HR, et al. Role of omentectomy and appendectomy in surgical staging of endometrioid endometrial cancer. Eur J Gynaecol Oncol. 2013; 34(4):322-4 [PubMed] Related Publications
PURPOSE: The purpose of this study was to determine whether it was necessary to add omentectomy and appendectomy to the surgical staging of endometrioid endometrial cancer. MATERIALS AND METHODS: Records were reviewed from June 2005 to June 2009 for endometrioid endometrial cancer patients who underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, infracolic omentectomy and appendectomy. RESULTS: In total, 186 patients were included in the analysis. Disease was limited to uterus in 93% of patients and 87% of patients had Stage I disease. There was only one omental metastasis and no appendix metastasis in all stages. CONCLUSION: Routine omentectomy and appendectomy are unnecessary in surgical staging of endometrioid endometrial cancer unless there is suspicion of gross metastases during intraoperative examination.
Koukoulomati A, Tsikouras P, Tsagias N, et al. Diagnostic approach and therapeutic management in early-stage endometrial cancer. Eur J Gynaecol Oncol. 2013; 34(4):319-21 [PubMed] Related Publications
OBJECTIVE: The effectiveness of pelvic and para-aortic lymphadenectomy in the morbidity of patients affected by early-stage endometrial carcinoma (EC) is the subject of this study. STUDY DESIGN: Ninety-two cases with endometrial cancer that underwent para-aortic and pelvic lymphadenectomy, from June 1995 to June 2006, were studied and compared with 30 cases of patients with endometrial cancer without lymphadenectomy. RESULTS: According to the results, systematic pelvic and para-aortic lymphadenectomies improved disease-free and overall survival rates among the patients with endometrial cancer. The mean number of removed para-aortic lymph nodes was 19.01 +/- 5.88, whereas the mean number of removed iliac lymph nodes was 32.94 +/- 6.69. Forty-two and 31 metastatic iliac and para-aortic nodes were found, respectively. No surgery-related deaths and major intraoperative injuries occurred. The frequency and the type of postoperative complications were not affected by the performance of lymphadenectomy. The morbidity rate was 6.2%, similar to the group without lymphadenectomy (5.79%). No recurrence occurred in the group with lymphadenectomy, while in the other group the recurrence rate was 23.3%. CONCLUSIONS: Lymph nodes metastases can be observed in early stages of EC. Pelvic and para-aortic lymphadenectomies seems to provide profound information about the Stage of the disease and the patient's survival, identifying which patients are suitable for supplementary treatment, without significant clinical increase of morbidity.
Boskovic V, Bozanovic T, Ljubic A, et al. Endometrial stromal sarcoma with intracaval extension at initial presentation. Eur J Gynaecol Oncol. 2013; 34(3):280-1 [PubMed] Related Publications
Endometrial stromal sarcoma (ESS) is a rare uterine neoplasm. Tumor involvement of the large vessels is extremely rare. This is a case report of ESS with tumor invasion of the inferior vena cava at initial presentation.
Litta P, Fabris AM, Breda E, et al. Laparoscopic surgical staging of endometrial cancer: does obesity influence feasibility and perioperative outcome? Eur J Gynaecol Oncol. 2013; 34(3):231-3 [PubMed] Related Publications
AIM: Laparoscopic treatment of early-stage endometrial cancer is the gold standard to reduce perioperative morbidity. Obesity is a well-known risk factor for endometrial cancer and anesthesiological and surgical complications. The authors' aim was to examine the effect of body mass index (BMI) on perioperative parameters and complications in laparoscopically-treated patients with endometrial cancer. MATERIALS AND METHODS: A consecutive series of patients affected by endometrial cancer and their demographic and clinicopathological data were collected. Patients were divided in 41 non-obese (BMI or= 30) groups. All patients had been preoperatively evaluated with hysteroscopic procedures and toraco-abdominal computed tomography (CT) and had been submitted to laparoscopic radical hysterectomy according to Querleu-Morrow, pelvic lymphadenectomy, peritoneal washing, and bilateral adnexectomy. RESULTS: There was no statistically significant difference in blood loss, number of lymph nodes removed, and hospital stay between the groups, but there was a trend towards a lengthening of surgical time in the obese women. There were no major intraoperative and postoperative complications. DISCUSSION: This study demonstrates that laparoscopic approach is feasible and safe in obese women evaluating the anesthesiological risk.
Apgar BS, Kaufman AJ, Bettcher C, Parker-Featherstone E Gynecologic procedures: colposcopy, treatments for cervical intraepithelial neoplasia and endometrial assessment. Am Fam Physician. 2013; 87(12):836-43 [PubMed] Related Publications
Women who have abnormal Papanicolaou test results may undergo colposcopy to determine the biopsy site for histologic evaluation. Traditional grading systems do not accurately assess lesion severity because colposcopic impression alone is unreliable for diagnosis. The likelihood of finding cervical intraepithelial neoplasia grade 2 or higher increases when two or more cervical biopsies are performed. Excisional and ablative methods have similar treatment outcomes for the eradication of cervical intraepithelial neoplasia. However, diagnostic excisional methods, including loop electrosurgical excision procedure and cold knife conization, are associated with an increased risk of adverse obstetric outcomes, such as preterm labor and low birth weight. Methods of endometrial assessment have a high sensitivity for detecting endometrial carcinoma and benign causes of uterine bleeding without unnecessary procedures. Endometrial biopsy can reliably detect carcinoma involving a large portion of the endometrium, but is suboptimal for diagnosing focal lesions. A 3- to 4-mm cutoff for endometrial thickness on transvaginal ultrasonography yields the highest sensitivity to exclude endometrial carcinoma in postmenopausal women. Saline infusion sonohysteroscopy can differentiate globally thickened endometrium amenable to endometrial biopsy from focal abnormalities best assessed by hysteroscopy. Hysteroscopy with directed biopsy is the most sensitive and specific method of diagnosing endometrial carcinoma, other than hysterectomy.
Mingels MJ, Geels YP, Pijnenborg JM, et al. Histopathologic assessment of the entire endometrium in asymptomatic women. Hum Pathol. 2013; 44(10):2293-301 [PubMed] Related Publications
Knowledge on the nature of the endometrium in women without symptoms of endometrial disease is poor. Therefore, the aim of this prospective study was to describe the endometrium of a cohort of asymptomatic women. The entire endometrium of premenopausal and postmenopausal women was embedded for histologic examination. All included patients underwent a hysterectomy on indication of uterovaginal prolapse, from July 2011 to October 2012, in 3 hospitals in the South of the Netherlands. Exclusion criteria were symptoms of postmenopausal vaginal blood loss or premenopausal disordered vaginal bleeding. As a result, 68 women were included in the study, 48 women were postmenopausal and 20 were premenopausal. In the endometrium of 10 women, simple hyperplasia was found (15%); 1, complex hyperplasia (2%); 2, simple atypical hyperplasia (3%); 2, complex atypical hyperplasia (3%); and 2, a small focus of intramucosal endometrioid endometrial carcinoma (3%). In general, the endometrium was heterogeneous, and most lesions were not present in the entire endometrium. In conclusion, after examining the entire endometrium, a remarkable high prevalence of endometrial pathology was found in asymptomatic women. The clinical meaning of these lesions is not yet clear, but endometrial pathology may frequently exist without symptoms.
Jiang H, Qu L, Liu X, et al. A comparison of laparoscopic and abdominal radical parametrectomy for cervical or vaginal apex carcinoma and stage II endometrial cancer after hysterectomy. JSLS. 2013 Apr-Jun; 17(2):249-62 [PubMed] Free Access to Full ArticleRelated Publications
BACKGROUND AND OBJECTIVE: Radical parametrectomy (RP), performed either abdominally (ARP) or laparoscopically (LRP), is a viable alternative to radiotherapy in treating invasive cervical cancer, vaginal apex cancer, and endometrial cancer that is more advanced than initially suspected after hysterectomy. We carried out a comparative study on intra- and postoperative parameters between the two performed by similarly experienced surgeons. METHODS: Forty consecutive patients indicative for RP were reviewed: 22 and 18 underwent ARP and LRP, respectively. Information was collected on demographics, indications for initial and this surgery, tumor characteristics, intra- and postoperative parameters, and complications. The lengths of resected parametrial and vaginal tissues were measured. RESULTS: Compared with ARP, LRP resulted in shorter operative time (200 vs 239 min), less blood loss (627.8 vs 929.5 mL), shorter hospital stay (16.8 vs 19.9 days), and removal of more pelvic lymph nodes (27.4 ± 5.9 vs 23.1 ± 7.1). Although it was not attempted in ARP to remove lymph nodes in the deep obturator space, it was attempted in LRP and one positive node was found. In the ARP cohort there was one case of injury to the small intestine during surgery, whereas in LRP there was one instance of lower urologic fistula after surgery. CONCLUSION: LRP is superior to ARP in terms of shorter operative time, less blood loss, and shorter hospital stay while still maintaining the completeness of the procedure. It can be safely performed in the hands of experienced surgeons for cervical or vaginal apex carcinoma and stage II endometrial cancer after hysterectomy.
Rauh-Hain JA, del Carmen MG Endometrial stromal sarcoma: a systematic review. Obstet Gynecol. 2013; 122(3):676-83 [PubMed] Related Publications
OBJECTIVE: To summarize available studies with respect to evaluation and management of patients with endometrial stromal sarcoma and undifferentiated endometrial sarcoma. DATA SOURCES: We conducted an electronic search of research articles published in English between January 1, 1981, and January 1, 2013, using MEDLINE, PubMed, and ClinicalTrials.gov (www.clinicaltrials.gov) databases. METHODS OF STUDY SELECTION: Of the 115 studies initially identified, 86 were chosen after limiting the review to those articles focusing on endometrial stromal sarcoma and crossreferencing to eliminate duplication. Review articles were excluded. Of the 86 studies meeting eligibility criteria, 84 were retrospective, one was a prospective phase II trial, and one was a phase III randomized study. Data were extracted systematically. Each of the reviewers assessed the quality of each study independently. TABULATION, INTEGRATION, AND RESULTS: Data were abstracted using standard abstraction templates to summarize study findings. Given the rarity of this tumor, we report available data with respect to epidemiology, pathogenesis, prognostic factors, and treatment. Endometrial stromal sarcoma and undifferentiated endometrial sarcoma comprise an estimated 1% of all uterine cancers and less than 10% of all uterine mesenchymal neoplasms. Hysterectomy and bilateral salpingo-oophorectomy is the cornerstone of treatment for early-stage (I or II) disease. Surgical resection when feasible may also be appropriate for patients presenting with advanced-stage tumors. The value of adjuvant therapy for early-stage disease remains unproven. Hormone therapy continues to be the most efficacious treatment modality for patients with advanced-stage or recurrent disease. CONCLUSION: Endometrial stromal sarcoma and undifferentiated endometrial sarcoma are rare tumors. Surgical resection is appropriate for patients with early-stage (I or II) disease and those with resectable, advanced-stage (III or IV) tumors. Hormone therapy may be appropriate in treating advanced and recurrent disease.
Galic V, Schiavone MB, Herzog TJ, et al. Prognostic significance of mucinous differentiation of endometrioid adenocarcinoma of the endometrium. Cancer Invest. 2013; 31(7):500-4 [PubMed] Related Publications
Using Surveillance, Epidemiology, and End Results database we identified 43,882 (97.0%) women with endometrioid adenocarcinomas and 1,374 (3.0%) with mucinous adenocarcinomas. Women with mucinous tumors were older (P < .0001), more often white (P = .04), and more often to present at advanced stage (P = .001). Survival was similar for both histologies; the hazard ratio for cancer-specific survival for mucinous compared to endometrioid tumors was 0.90 (95% CI, 0.74-1.09) while the hazard ratio for overall survival was 0.95 (95% CI, 0.85-1.07). Five-year survival for stage I mucinous tumors was 89.9% (95% CI, 87.6-91.9%) compared to 89.0% (95% CI, 88.6-89.4%) for endometrioid tumors.
Simmons AR, Baggerly K, Bast RC The emerging role of HE4 in the evaluation of epithelial ovarian and endometrial carcinomas. Oncology (Williston Park). 2013; 27(6):548-56 [PubMed] Related Publications
HE4 (human epididymis protein 4) is overexpressed in both ovarian and endometrial cancers. Levels of the shed HE4 protein are elevated in sera from ovarian and endometrial cancer patients. HE4 is less frequently elevated than cancer antigen 125 (CA 125) in benign gynecologic conditions and is found in a fraction of endometrial and ovarian cancers that lack CA 125 expression. Consequently, HE4 has emerged as an important biomarker that complements CA 125 in discriminating between benign and malignant pelvic masses, monitoring response to treatment, and detecting recurrences of both ovarian and endometrial cancer. The "risk of ovarian malignancy algorithm" (ROMA) incorporates CA 125, HE4, and menopausal status to distinguish benign from malignant adnexal masses, and has been approved by the US Food and Drug Administration to aid in referring patients who are likely to have ovarian cancer to specially trained gynecologic oncologists for surgery. HE4 also promises to augment the sensitivity of CA 125 for detecting early-stage ovarian cancer. In this review, we discuss the discovery and biologic significance of HE4 and evaluate available evidence regarding the utility of HE4 as a biomarker for ovarian and endometrial cancer.
Grabosch S, Xynos F Isolated port-site metastasis after robotic hysterectomy for stage IA endometrial adenocarcinoma. Obstet Gynecol. 2013; 122(2 Pt 2):437-9 [PubMed] Related Publications
BACKGROUND: Port-site metastasis is a known complication of laparoscopic surgery, although it has been described less in robotic surgery. There are limited reports of such occurrences in current literature. CASES: Two patients underwent robotic-assisted total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and lymph node dissection for stage IA endometrial cancer. One patient's surgery was complicated by uterine perforation but the other surgery was uncomplicated. Both patients had development of isolated port-site metastasis and required resection followed by chemotherapy and radiation. CONCLUSION: Port-site metastasis is a surgical complication with an unclear etiology. There are no clear data to suggest a lower incidence with robotic surgery. Patients at low risk for recurrence still may experience development of port-site metastasis.
Lee MH, Aquino-Parsons C, Hoskins PJ, et al. Preoperative radiotherapy for inoperable stage II endometrial cancer: insights into improving treatment and outcomes. J Obstet Gynaecol Can. 2013; 35(7):635-9 [PubMed] Related Publications
OBJECTIVE: To review recurrence patterns and survival outcomes of women receiving preoperative radiotherapy for clinical stage II endometrial cancer in British Columbia. METHODS: We performed a retrospective population-based cohort study of all patients with clinical stage II endometrial cancer who were referred to the British Columbia Cancer Agency from 2000 to 2008, deemed ineligible for primary surgery, and therefore offered preoperative radiotherapy followed by surgery. Patient demographics, uterine risk factors, timing and details of treatments, and timing and sites of recurrence were obtained from patient records. Primary outcome measures were the sites and rates of recurrence and recurrence-free survival. RESULTS: We identified 29 patients with a mean age of 61 years (range 41 to 83) and median follow-up of 3.1 years (range 0.3 to 5.3). Three-year overall survival was 79%, and median recurrence-free survival was 2.5 years. Eight patients had recurrence of disease (27.6%), with a median time to recurrence of 1.3 years, (range 0.4 to 2.7). Six of these eight women had two or more high-risk uterine factors (deep myometrial invasion, grade 3 tumour), ovarian involvement, or adverse histological type (carcinosarcoma), compared with only one of 21 patients without recurrence. Seven of eight women had recurrence outside the radiated volume of tissue. Median survival after recurrence was 1.0 years (range 0.4 to 2.2). CONCLUSIONS: Women with clinical stage II endometrial cancer had a significant risk of recurrence when treated with preoperative radiotherapy followed by surgery. They were more likely to have distant recurrences, implying the need for an alternate treatment paradigm.
Korani M, Fallah S, Tehranian A, et al. The evaluation of the FOXO1, KLF9 and YT521 genes expression in human endometrial cancer. Clin Lab. 2013; 59(5-6):483-9 [PubMed] Related Publications
BACKGROUND: The current study was designed to explore the changes of the mRNA levels of the YT521, Forkhead box protein O1 (FOXO1), and Krüppel-like factor 9 (KLF9) proteins in human normal and cancerous endometrial tissue. METHODS: The study was conducted in 30 premenopausal patients diagnosed with endometrial cancer and 20 premenopausal women with no clinically documented abnormalities of the endometrium undergoing hysterectomy. Gene expression levels were assayed using quantitative real-time PCR. RESULTS: The endometrial tissue FOXO1 mRNA level (0.82 +/- 0.27) of patients with endometrial cancer was significantly lower (p < 0.001) than controls (4.51 +/- 2.68). In subjects with endometrial cancer the KLF9 mRNA level (1.12 +/- 0.38) was lower (p < 0.001) when compared to controls (3.11 +/- 1.52). A remarkable (not significant, p = 0.069) increase was found in the YT521 mRNA level of patients' endometrial tissue (11.19 +/- 3.99) in comparison with the control subjects (8.82 +/- 5.01). No significant difference was detected for the FOXO1, KLF9 and YT521 mRNA levels of the endometrial tissue of patients with cancer at different stages. CONCLUSIONS: It is suggested that the alteration of the gene expression profiles of FOXO1, KLF9 and YT521, which occur in human endometrial cancers likely play a crucial role in initiation of cancer.
Batool S, Manzur S, Raza S Accuracy of Doppler ultrasound in diagnosis of endometrial carcinoma. J Pak Med Assoc. 2013; 63(1):28-31 [PubMed] Related Publications
OBJECTIVE: To determine the accuracy of Doppler ultrasound in the diagnosis of endometrial carcinoma in patients presenting with post-menopausal bleeding while taking histopathological findings as the gold standard. METHODS: The cross-sectional study was done at the Department of Radiology, Bahawal Victoria Hospital, Bahawalpur, from April 1 to September 30, 2009, and comprised 128 patients above 50 years of age having history of post-menopausal bleeding and who were referred to the department. Name, age and hospital registration number were recorded on a proforma. Doppler ultrasound was performed and endometrial thickness and uterine artery resistive index were recorded on transabdominal ultrasonography. Patients with endometrial thickness of more than 5 mm and uterine artery resistive index of less than 0.7 were considered to be having endometrial carcinoma. Histopathology findings were also recorded using the hospital registration number of the patient. The findings of Doppler ultrasound scan were validated with the findings of histopathology. RESULTS: Of the 128 patients, 48 (37.5%) were between the ages of 51 and 55 years; 46 (35.93%) were in the 56-60 age group; and 34 (26.57%) were over 65 years. On the basis of Doppler ultrasound findings, 106 (82.8%) patients were diagnosed as having endometrial carcinoma, while 22 (17.19%) were declared negative. Ultrasonography results were compared with histopathology findings. The percentages of true positive, true negative, false positive and false negative were calculated. There were 103 (80.47%) true positive; 12 (9.37%) false positive; 10 (7.81%) true negative; and 3 (2.35%) false negative. Specificity, sensitivity, positive predictive value and negative predictive value were found to be 97.16%, 76%, 89.56% and 76.92% respectively. CONCLUSION: The use of Doppler ultrasonography in non-invasive diagnosis of endometrial carcinoma in patients presenting with post-menopausal bleeding was quite useful with good sensitivity, specificity, as well as positive and negative predictive values. There were no procedural complications.
Squillaci S, Marchione R, Piccolomini M, et al. Uterine endometrioid adenocarcinoma with extensive pilomatrixoma-like areas. A case report. Pathologica. 2013; 105(1):8-10 [PubMed] Related Publications
Shadow cells are typical features of pilomatrixoma, although they have been described in other benign cutaneous tumours with characteristics of differentiation toward the hair matrix. The finding of extensive shadow cell differentiation in visceral carcinomas is otherwise unusual. We report herein a case of uterine adenocarcinoma with extensive pilomatrixoma-like areas in a 74-year-old woman. The endometrial tumour showed an invasive poorly differentiated growth with squamous differentiation deeply extending into the myometrium intermixed with lobules of empty squamoid polyhedral cells with clear shadow like nuclei, focally exhibiting a 'ghost' appearance. The cervix, salpinges, ovaries and pelvic lymph nodes were free of disease and, taking all evidence into account, the tumour was diagnosed as poorly differentiated endometrial endometrioid adenocarcinoma (FIGO stage IB). The recognition of an extensive pilomatrixoma-like component in a high- grade endometrioid adenocarcinoma may be important to avoid diagnostic misinterpretation with uterine metastases of malignant cutaneous pilomatrical tumours, such as pilomatrix carcinomas.
He H, Bhosale P, Wei W, et al. MRI is highly specific in determining primary cervical versus endometrial cancer when biopsy results are inconclusive. Clin Radiol. 2013; 68(11):1107-13 [PubMed] Related Publications
AIM: To evaluate utility of magnetic resonance imaging (MRI) in determining the primary site of endometrial versus cervical tumours when the biopsy results are inconclusive. MATERIAL AND METHODS: Forty-eight patients who underwent a total hysterectomy for unknown primary adenocarcinoma of the uterus after endometrial and/or endocervical biopsies were included in the study. The 48 available pelvic MRI images were reviewed by two body radiologists independently and jointly to resolve discordance, blinded to any clinical and pathological information. The clinical information and histopathology were reviewed by a radiology fellow and a pathologist specializing is gynaecological oncology. The final surgical pathology was used as the reference standard to confirm the origin of the primary tumour. RESULTS: The radiologists correctly identified the primary sites in 85% of the cases (41/48). There was substantial agreement between the two readers (kappa statistics = 0.79). Both radiologists found that T2 and dynamic T1-weighted images (WI) were most helpful in making the diagnosis, and dynamic T1WI helped resolve problematic cases. The sensitivity and specificity for detecting endometrial and cervical cancer on MRI were 88% and 88% and 75% and 93%, respectively. CONCLUSION: MRI has high sensitivity and specificity in determining the origin of the primary endometrial versus cervical tumours when endometrial/endocervical curettage is inconclusive.
Mirantes C, Espinosa I, Ferrer I, et al. Epithelial-to-mesenchymal transition and stem cells in endometrial cancer. Hum Pathol. 2013; 44(10):1973-81 [PubMed] Related Publications
This review article describes the main features of epithelial-to-mesenchymal transition (EMT) and its possible role in understanding myometrial invasion in endometrial carcinoma (EC), as well as the development of malignant mixed Müllerian tumor (MMMT). Moreover, the article discusses the possible role of somatic (SSC) and cancer stem cells (CSC) in EC. Different transcriptional repressors of E-cadherin have been identified in EMT, including Snail and Slug, ZEB1 and ZEB2, and E47 and Twist. The expression of some of these genes is increased at the myoinvasive front and correlates inversely with E-cadherin inmunoreactivity. Whereas the transient occurrence of the EMT phenomenon is important for myometrial invasion in conventional EC, MMMT shows permanent expression of EMT leading to repression of E-cadherin and increased expression of mesenchymal markers including proteins involved in skeletal muscle development. An SSC population, identified as a side population, assessed by the Hoechst dye exclusion test has been identified in human endometrium. CSCs have been defined in analogy to SSC as cancer cells that have the capacity to self-renew, which means undergoing divisions that allow the generation of more identical CSCs and give rise to the variety of more differentiated cells found in the malignancy. Although published data show that CD133(+) cells retain the characteristics of CSC, there is no conclusive evidence showing that CD133 is the universal marker for EC stem cells. Finally, a possible role for endometrial stem cells in the development of ovarian endometriosis and ovarian endometrioid carcinoma is commented.
Sieh W, Köbel M, Longacre TA, et al. Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study. Lancet Oncol. 2013; 14(9):853-62 [PubMed] Related Publications
BACKGROUND: Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival. METHODS: 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study. Participants included in our analysis had been diagnosed with invasive serous, mucinous, endometrioid, or clear-cell carcinomas of the ovary. For a patient to be eligible, tissue microarrays, clinical follow-up data, age at diagnosis, and tumour grade and stage had to be available. Clinical data were obtained from medical records, cancer registries, death certificates, pathology reports, and review of histological slides. PR and ER statuses were assessed by central immunohistochemistry analysis done by masked pathologists. PR and ER staining was defined as negative (<1% tumour cell nuclei), weak (1 to <50%), or strong (≥50%). Associations with disease-specific survival were assessed. FINDINGS: 2933 women with invasive epithelial ovarian cancer were included: 1742 with high-grade serous carcinoma, 110 with low-grade serous carcinoma, 207 with mucinous carcinoma, 484 with endometrioid carcinoma, and 390 with clear-cell carcinoma. PR expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001) and high-grade serous carcinoma (log-rank p=0·0006), and ER expression was associated with improved disease-specific survival in endometrioid carcinoma (log-rank p<0·0001). We recorded no significant associations for mucinous, clear-cell, or low-grade serous carcinoma. Positive hormone-receptor expression (weak or strong staining for PR or ER, or both) was associated with significantly improved disease-specific survival in endometrioid carcinoma compared with negative hormone-receptor expression, independent of study site, age, stage, and grade (hazard ratio 0·33, 95% CI 0·21-0·51; p<0·0001). Strong PR expression was independently associated with improved disease-specific survival in high-grade serous carcinoma (0·71, 0·55-0·91; p=0·0080), but weak PR expression was not (1·02, 0·89-1·18; p=0·74). INTERPRETATION: PR and ER are prognostic biomarkers for endometrioid and high-grade serous ovarian cancers. Clinical trials, stratified by subtype and biomarker status, are needed to establish whether hormone-receptor status predicts response to endocrine treatment, and whether it could guide personalised treatment for ovarian cancer. FUNDING: Carraresi Foundation and others.
Kim MK, Seong SJ, Song T, et al. Comparison of dilatation & curettage and endometrial aspiration biopsy accuracy in patients treated with high-dose oral progestin plus levonorgestrel intrauterine system for early-stage endometrial cancer. Gynecol Oncol. 2013; 130(3):470-3 [PubMed] Related Publications
OBJECTIVE: To compare the diagnostic accuracy of dilatation & curettage (D&C) vs. endometrial aspiration biopsy in follow-up evaluation of patients treated with high-dose oral progestin plus levonorgestrel intrauterine system (LNG-IUS) for early-stage endometrial cancer (EC). METHOD: A prospective observational study was conducted with 11 patients with FIGO grade 1 or 2, clinical stage IA endometrioid adenocarcinoma. Patients were aged up to 40 years wishing to preserve fertility treated with high-dose oral progestin plus LNG-IUS. Treatment response assessment was done at three month intervals. Endometrial tissues were obtained via endometrial aspiration biopsy with LNG-IUS in place and D&C after removal of LNG-IUS. We identified 28 cases; the histologic results were compared. Kappa statistics were used to assess the agreement of two methods. RESULTS: Diagnostic concordance between examinations was assessed for 9 out of 28 cases examined (32.1%). These consisted of three cases with both examination results of normal, 3 cases with endometrioid adenocarcinoma, 1 case with complex endometrial hyperplasia, 2 cases with material insufficient for diagnosis. Endometrioid adenocarcinoma on D&C was diagnosed in 9 out of 28 cases, but from endometrial aspiration biopsy, only 3 of these 9 cases were diagnosed with endometrioid adenocarcinoma, giving the diagnostic concordance at 33% (kappa value=0.27). From endometrial aspiration biopsy, 17 out of 28 cases (60.7%) had material insufficiency for diagnosis. CONCLUSION: In patients treated with high-dose oral progestin plus LNG-IUS for early-stage EC, endometrial aspiration biopsy with LNG-IUS in place may be not reliable as a follow-up evaluation method.
Brucka A, Szyłło K Immunoexpression of the PTEN protein and matrix metalloproteinase-2 in endometrial cysts, endometrioid and clear cell ovarian cancer. Ginekol Pol. 2013; 84(5):344-51 [PubMed] Related Publications
OBJECTIVES: Endometrioid and clear cell ovarian adenocarcinomas are suspected to derive from ectopic endometrial foci. The aim of the study was to determine PTEN and MMP-2 immunoexpression in endometrial ovarian cysts, endometrioid and clear cell ovarian carcinomas and to assess the relationship between the abovementioned values and clinical data of patients in order to find the marker of increased risk of malignant proliferation based on ovarian endometriotic lesions. Detailed analysis of the collected data was conducted to investigate the correlation between immunohistochemical expression of the examined antigens, histopathological diagnosis and clinical condition of patients. MATERIAL AND METHODS: 20 endometrial adenocarcinomas, 21 clear cell ovarian cancers and 26 endometrial cysts were included in the study The control group consisted of 29 specimens of physiological endometrium: 16 samples of the proliferative phase and 13 samples of the secretory phase. Protein expression of PTEN and MMP-2 was evaluated by immunohistochemistry Protein immunoexpression in the collected specimens was estimated with the use of light microscope and MultiScan software. Immunoreactivity of the PTEN antigen was assessed by the quantitative method, whereas MMP-2 immunoexpression was evaluated by the semi-quantitative method. Two-sided tests were used for statistical inference. Generalized linear models were used to compare the studied groups. Error distributions were selected using the Akaike criterion (AIC). Statistical analysis was conducted with the use of the R Statistical Package. RESULTS: MMP-2 immunoreactivity differed significantly between the study groups and controls (p<0.001). PTEN immunoexpression was the strongest in endometrial cysts (53.7 %), lower in clear cell cancers (50.2%) and the lowest in endometrioid adenocarcinomas (43.88%), but the differences were not statistically significant (p=0.17). PTEN reactivity in the group of endometrioid carcinomas was significantly higher (p=0.02), while MMP-2 expression had a falling tendency (p=0.076) in obese women. CONCLUSIONS: Increased MMP-2 expression in the successive groups may imply a rising invasive potential of the epithelial cells in endometrial cysts, endometrioid and clear cell adenocarcinomas. Strong immunoreactivity for PTEN in proliferative endometrium implies its role in the regulation of endometrial proliferation. PTEN activity may reduce MMP-2 expression in insulin resistant women suffering from endometrial ovarian cancer Simultaneous evaluation of PTEN and MMP-2 immunoexpression in ectopic endometrial foci cannot be used to identify women with an increased risk of neoplastic transformation.
Elliot E Supporting patients following pelvic radiotherapy for endometrial cancer. Br J Nurs. 2013 May 23-Jun 12; 22(10):S24, S26-30 [PubMed] Related Publications
Endometrial cancer is the commonest gynaecological cancer in the UK. Affected women often live with long-term complex and debilitating side-effects of radiotherapy treatment, such as bowel toxicity, fatigue and psychosexual problems. Women also experience negative feelings around self-image and sexuality, which contribute to a decline in their quality of life. A review of the literature and national policy showed that women had unmet needs after completing radiotherapy treatment for endometrial cancers, and that cancer nurse specialists are in a prime position to deliver a holistic package of personalized care. Staff at a nurse-led gynaecology oncology clinic performed an audit that found the clinic was not meeting the longer-term needs of most women after radiotherapy for endometrial cancers, and that women were attending multiple appointments to access different services. The clinical nurse specialist reviewed local and national policy, carried out situational analysis and engaged with service users to identify where change was needed and to examine whether a new model of service provision, where patients could consult different professionals at one appointment, would help the move forward in life after treatment.
Guo T, Li B, Gu C Expression of hPEBP4 negatively correlates with estrogen and progesterone receptors in endometrial carcinoma. J BUON. 2013 Apr-Jun; 18(2):465-70 [PubMed] Related Publications
PURPOSE: To investigate the expression of human phosphatidylethanolamine- binding protein 4 (hPEBP4) in endometrial carcinoma and its relation with progesterone receptor (PR) and estrogen receptor (ER). METHODS: Forty-five samples of endometrioid endometrial carcinoma (EEC), 12 samples of atypical endometrial hyperplasia, and 30 samples of normal endometrium were examined. Samples were studied by immunohistochemistry for PR, ER and hPEBP4 expression. Expressions were statistically quantified and analyzed. RESULTS: Expressions of PR and ER were significantly higher in normal endometrium than in cancer. Expression of hPEBP4 was significantly lower in normal endometrium. The expression of hPEBP4 was significantly higher in advanced-stage endometrial cancer, whilst higher but insignificant trend was noticed in higher grade carcinoma. Statistically insignificant trend of negative ER and PR expression with higher grade or stage was noticed. The expression of hPEBP4 was negatively correlated to ER and PR in EEC. CONCLUSION: The expression pattern of hPEBP4 indicated that hPEBP4 interacted with ER and PR in EEC and could thus become a possible target for the development of novel treatment against this malignancy.
Hubbs JL, Saig RM, Abaid LN, et al. Systemic and local hormone therapy for endometrial hyperplasia and early adenocarcinoma. Obstet Gynecol. 2013; 121(6):1172-80 [PubMed] Related Publications
OBJECTIVE: To estimate disease regression, persistence, and progression in women with complex endometrial hyperplasia and stage I endometrial carcinoma treated with a levonorgestrel-releasing-intrauterine system or oral progesterone. METHODS: Records of all patients who received progestin therapy for endometrial hyperplasia or early-stage endometrioid cancer between January 1999 and July 2011 were reviewed. Demographic data (age, body mass index), presentation, treatment modality and rationale, rates of response, recurrence, and salvage surgery were collected and compared using Student's t and χ tests. Fertility outcomes when available were analyzed. RESULTS: One hundred eighty-six women received primary hormone therapy for endometrial hyperplasia or cancer. Of these, 153 had adequate follow-up without surgery or radiation as part of primary treatment. Average age at diagnosis was 49.6 years (range 22-92 years). The most common reasons cited for hormone therapy were medical comorbidities (46%) and fertility (21%). Patients with hyperplasia compared with cancer had significantly different complete response (66-70% compared with 6-13%), initial response with recurrence (11-23% compared with 19-30%), and no response rates (11-19% compared with 57-75%), respectively (P<.001). Outcomes were not significantly different between the levonorgestrel-releasing intrauterine system and oral progesterone among patients with cancer at all time points. In patients with hyperplasia, outcomes were not significantly different except during the 9-month to 12-month assessment where those who received systemic hormones were less likely to have disease persistence or progression compared with patients who had levonorgestrel-releasing intrauterine systems. Three patients achieved pregnancy. CONCLUSIONS: Hormone therapy has varied response rates among women with endometrial hyperplasia or cancer who do not undergo surgery. Close patient monitoring remains paramount given the high recurrence and high percentage of patients who will not respond.
Milgrom SA, Kollmeier MA, Abu-Rustum NR, et al. Postoperative external beam radiation therapy and concurrent cisplatin followed by carboplatin/paclitaxel for stage III (FIGO 2009) endometrial cancer. Gynecol Oncol. 2013; 130(3):436-40 [PubMed] Related Publications
OBJECTIVE: The optimal adjuvant therapy in advanced endometrial cancer is controversial. One regimen is concurrent external beam pelvic irradiation (RT) and cisplatin, then carboplatin/paclitaxel. This study reports an institutional experience using this approach in stage III (FIGO 2009) endometrial cancer. METHODS: Patients with stage III (FIGO 2009) endometrial cancer who underwent total hysterectomy and bilateral salpingo-oophorectomy at a single institution from 01/2004 to 12/2009 were identified retrospectively. Those treated with adjuvant RT/cisplatin, followed by carboplatin/paclitaxel comprised the study population. RESULTS: Of the 40 eligible patients, 7 (18%) were stage IIIA and 33 (82%) IIIC. Nineteen patients (48%) were ≥ 60 years of age. Twenty-three (58%) had ≥ 50% myometrial invasion, 30 (75%) lymphovascular invasion, 11 (28%) cervical stromal invasion, and 5 (12%) positive peritoneal cytology. Histology was endometrioid in 32 (80%), serous in 6 (15%), and clear cell in 2 (5%). At a median follow-up of 49 months, the 5-year freedom from relapse was 79% and overall survival 85%. The 5-year rate of vaginal recurrence was 3%, non-vaginal pelvic recurrence 3%, para-aortic recurrence 11%, peritoneal recurrence 5%, and other distant recurrence 11%. Thirty-one patients (78%) were able to complete the planned RT/cisplatin and 4 cycles of carboplatin/paclitaxel. Acute grade 3 toxicity occurred in 10 patients (4 neutropenia, 2 anemia, 1 fatigue, 2 diarrhea). No late toxicity was grade ≥ 3. CONCLUSION: These favorable outcomes corroborate those of RTOG 9708. Until prospective data that compare adjuvant therapy regimens mature, concurrent chemoradiation should be strongly considered in stage III endometrial cancer.