Estrogen and progesterone receptors in uterine sarcomas

Estrogen and progesterone receptors were measured in tissues from 43 patients with various uterine sarcomas using the dextran-coated charcoal assay. Estrogen receptor was present in 55.5% and progesterone receptor in 55.8% of samples, at median estrogen and progesterone receptor concentrations of 10.7 and 15.8 fmol/mg cytosol protein, respectively. These median values are much lower than those in 30 consecutive endometrial adenocarcinomas and 50 breast carcinomas assayed in our laboratory. Progesterone receptor status correlated strongly with estrogen receptor status in uterine sarcomas (P = .001). Estrogen and progesterone receptor levels were not influenced by stage, grade, or mitotic count. Patients 50 years of age or less had significantly higher progesterone receptor than those over 50. No such age effect was seen for estrogen receptor. Endometrial stromal sarcoma had higher estrogen and progesterone receptor levels than other histologic types. Low-grade endometrial stromal sarcomas had higher median estrogen receptors (238.9 fmol/mg) and better survival (all patients alive at 6-12 months) than did high grade (N = 7) endometrial stromal sarcomas (median ER = 6.6 fmol/mg, all dead of disease at 8-27 months). For all histologic types, evaluable patients with stage I or II disease (N = 16) were more likely to survive longer than one year than those with stage III or IV disease (N = 13, P = .003). Evaluable patients with estrogen receptor-positive sarcomas were more likely to survive longer than one year than those with estrogen receptor-negative tumors (P = .006). With one exception, an endometrial stromal sarcoma, hormonal therapy exerted no beneficial effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estrogen receptor expression in an endometrial stromal sarcoma after tamoxifen therapy

INTRODUCTION: Several cases of low-grade endometrial stromal sarcomas in women with breast cancer have been reported to be associated with tamoxifen therapy. Estrogen receptor expression has been used to characterize the partial estrogenic action of tamoxifen on the endometrium and has been found in tamoxifen-associated endometrial pathologies. CASE: A low-grade endometrial stromal sarcoma in a woman with a history of breast cancer treated with adjuvant tamoxifen is presented. Steroid receptor studies performed on the tumor were negative for estrogen and positive for progesterone. CONCLUSION: The absence of estrogen receptor expression suggests that endometrial stromal sarcomas are not necessarily caused by the estrogenic properties of tamoxifen.     

Adjuvant chemotherapy following surgery in the management of uterine sarcomas

OBJECTIVE: The aim of this study was to investigate the use of imaging tools in the diagnosis of uterine sarcomas, and to evaluate the effect of the adjuvant chemotherapy for uterine sarcomas. PATIENTS AND METHODS: The data of 29 patients with uterine sarcomas who received cytostatic polychemotherapy between 1990 and 2000 at the Oncological Division of the Ist Department of Obstetrics and Gynecology, Semmelweis University were evaluated by the authors. Symptoms leading to diagnosis and methods of diagnosis were examined. Vascular changes shown by two-dimensional, color and pulsed Doppler ultrasonography were observed. For staging the currently accepted FIGO method was adopted. Most of the patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH & BSO). In each case we administered adjuvant combination chemotherapy according to the CYVADIC-protocol. The effect of adjuvant chemotherapy was evaluated. RESULTS: Six patients had Stage I, ten had Stage II, 11 had Stage III, and two had Stage IV disease. The mean age of the patients was 53.6 years with a range of 22 to 77 years. Histopathologic distribution included nine leiomyosarcomas (LMS), 13 mixed mesodermal sarcomas (MMS), and seven endometrial stromal sarcomas (ESS). Although most patients experienced neutropenia following cytotoxic chemotherapy, other non-hematologic adverse effects were easy to control. The average progression-free interval was 22.14 months, in which no significant difference was found between the histologic types. Different stages showed highly varied responses: surprisingly, patients in Stage IV with lung metastases were documented to have the longest progression-free survival. The three-year survival rate for all stages was demonstrated in 34.4% of cases. Patients with progressive disease had an average survival period of 4.4 months. CONCLUSIONS: These findings suggest that adjuvant cytostatic therapy for patients with distant metastasis confined to a single organ may produce better results than expected.     

Endometrial "sarcomas" complicating ovarian thecoma, polycystic ovarian disease and estrogen therapy

Unopposed endogenous and exogenous estrogenic stimulation has been considered by most investigators to have a role in the pathogenesis of carcinoma of the endometrium. Although a few cases of "sarcomas" of the endometrium that had developed in an estrogenic setting have been reported, a clear-cut association between estrogenic stimulation and these forms of endometrial cancer has not been established. We report six cases of endometrial sarcomas complicating ovarian thecomas, polycystic ovarian disease, or prolonged estrogen therapy. Three ovarian thecomas, which are considered to be estrogenic tumors, were associated with endometrial malignant mullerian mixed tumor, mullerian adenosarcoma, and low-grade stromal sarcoma in postmenopausal women. Polycystic ovarian disease, a condition characterized by unopposed estrinism due to the peripheral conversion of excessive androstenedione to estrone, was found in a 27-year-old infertile woman with an endometrial malignant mullerian mixed tumor. A pure osteogenic sarcoma of endometrial stromal origin developed in a 28-year-old woman with gonadal dysgenesis (Turner's syndrome) who had received estrogens for 18 years. The sixth woman, with an empty sella turcica after radiation therapy of a pituitary adenoma, had an endometrial mullerian adenosarcoma at the age of 40 years after 16 years of estrogen therapy. None of these patients had had pelvic radiation therapy. The evidence from this series of cases and from six additional cases identified in the literature suggests that the risk of endometrial sarcomas may be increased by estrogen therapy or endogenous disorders that lead to unopposed estrogenic stimulation of the uterus.     

Endometrial stromal sarcoma: objective response to letrozole

BACKGROUND: Low-grade endometrial stromal sarcoma is generally an indolent tumor rich in estrogen and progesterone receptors. Objective responses to hormonal therapy, most commonly with megestrol acetate, have been reported. CASE: The patient is a 51-year-old woman who presented with low-grade endometrial stromal sarcoma confined to the uterus in 1991 and was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Approximately 5 years later, the patient had recurrent pelvic disease treated with radiation therapy, followed by an attempt at resection. She was treated with megestrol acetate during the period she received radiation therapy with poor tolerance. Tamoxifen was then given with no tumor response. Megestrol acetate was restarted with progression of disease in the pelvis and abdomen. Letrozole was then given at a daily dose of 2.5 mg with partial response for a duration of 9 months. CONCLUSION: Letrozole at a daily dose of 2.5 mg may be effective in low-grade endometrial stromal sarcoma with positive estrogen receptors.     

Comparison of the clinical behavior of newly diagnosed stages II-IV low-grade serous carcinoma of the ovary with that of serous ovarian tumors of low malignant potential that recur as low-grade serous carcinoma

BACKGROUND: Serous ovarian tumors of low malignant potential (STLMP) frequently coexist with low-grade serous carcinoma of the ovary (LGSC) and, when they recur, frequently do so as LGSC. The purpose of this study was to compare the outcomes of patients with these two tumor types. METHODS: All patients with stages II-IV LGSC (group 1) or with STLMP that recurred as LGSC (group 2) seen at our institution from 1973 to 2003 were identified, and demographic data were obtained. For group 1, progression-free and overall survival times were calculated from the date of primary diagnosis to the date of disease progression/recurrence or the date of last contact/death, respectively. For group 2, progression-free and overall survival times were calculated from the date of first relapse as a LGSC to the date of progression or the date of last contact/death, respectively. The method of Kaplan and Meier was used to estimate survival, and the log-rank test was used to compare differences between survival curves. RESULTS: We identified 112 patients in group 1 and 41 in group 2. There were no statistically significant differences between the two groups in median age (42.7 vs. 45.4 years [at relapse]; P=0.37), progression-free survival time (19.5 vs. 25 months; P=0.92), or overall survival time (81.8 vs. 82.8 months; P=0.84). CONCLUSIONS: The age at diagnosis, progression-free survival time, and overall survival time associated with newly diagnosed stages II-IV LGSC of the ovary are similar to those of STLMP that recur as LGSC, providing further evidence of an association between these two tumor types.     

Melphalan, 5-fluorouracil, and medroxyprogesterone acetate in metastatic endometrial carcinoma

Fifty consecutive patients with recurrent and metastatic endometrial carcinoma were treated with melphalan, 5-fluorouracil, and medroxyprogesterone acetate with or without tamoxifen as first-line chemotherapy. The objective response rate was 48%, with 20% complete responses. The estimated median progression-free survival time was only five months (0.5 to 65 months) with estimated two- and five-year progression-free survival rates of 16 and 13%, respectively. The estimated median progression-free survival time was 24 months for complete responders; the progression-free survival times were significantly longer than the survival times (median = four months) for all other patients (P = .0002). Whether or not the addition of cytotoxic chemotherapy to progesterone hormonal therapy for metastatic endometrial carcinoma lengthens survival time is still open to question.     

子宫内膜间质肿瘤19例病理形态分析

目的 加深对子宫内膜间质肿瘤病理形态的认识。方法 对1例间质结节、15例低度恶性及3例高度恶性间质肉瘤进行临床病理分析。结果 肉瘤组中4例以粘膜下肿物为主要表现，4例手术后复发。病理检查4例有宫外病灶，6例伴有性索样分化，7例有明显的平滑肌分化。结论 低度恶性间质肉瘤是子宫内膜间质肿瘤的主要表现形式，性索样分化与平滑肌分化在间质肿瘤中不少见。     

Prognostic parameters in endometrial stromal sarcoma: a clinicopathologic study in 31 patients

OBJECTIVE: The aim of this study was to evaluate the behavior of endometrial stromal sarcomas (ESS) in relation to their clinical and pathologic features and to identify possible prognostic factors. METHODS: Thirty-one patients with histologically proven ESS were included in the analysis. Endometrial stromal sarcoma is characterized by proliferations composed of cells with endometrial stromal cell differentiation. A breakpoint of 10 mitoses per 10 high-power fields was used in the statistical analysis to distinguish between low-grade and high-grade endometrial stromal sarcoma and to evaluate the prognostic value of mitotic count in patients with ESS. RESULTS: The median follow-up time was 72 months (range 34-110). The median overall survival of the 31 patients was 127 months, resulting in a 5-year overall survival rate of 62%. Adjuvant therapy was administered to 25 patients; among those, 20 patients received postoperative radiotherapy and 5 patients received chemotherapy. Ten of the irradiated patients and 3 patients undergoing chemotherapy developed disease recurrence. Concerning the response rate to adjuvant chemotherapy, 1 patient showed a complete response, 1 patient a partial response, 1 patient stable disease, and 2 patients progressive disease. Altogether, 14 patients developed recurrent disease with a median disease-free survival of 11 months (range 5-60). Twelve patients died of the disease. A univariate model revealed that early tumor stage (P < 0.0007), low myometrial invasion (P < 0.008), and low mitotic count (P < 0.005) were associated with a lengthened overall survival in patients with endometrial stromal sarcoma. Age and adjuvant therapy did not influence overall survival of patients with ESS. CONCLUSION: Early tumor stage, low myometrial invasion, and low mitotic count are associated with a lengthened overall survival in patients with ESS.     

Laparoscopic oophorectomy either with or without hysterectomy for early breast cancer

OBJECTIVES: The aim of this study was to assess the surgical results, complications and pathological findings of laparoscopic ovarian ablation either with or without hysterectomy in women with early-stage breast cancer (BC). METHODS: Ninety women in early breast cancer stage who underwent laparoscopic bilateral salpingo-oophorectomy (BSO) either with or without hysterectomy were identified in a retrospective study conducted between January 2000 and December 2006. Tamoxifen antiestrogen therapy was used prior to hysterectomy. RESULTS: Forty-eight consecutive patients underwent laparoscopic hysterectomy with bilateral salpingo-oophorectomy and 42 with ovarian ablation only. The mean operative time for the laparoscopic hysterectomy and bilateral salpingo-oophorectomy or BSO alone was 82 min and 47.8 min, respectively. Blood loss was minimal in both groups (range: 20-250 ml). The rate of postoperative complications was very low (4.4%). One of all ovaries removed by laparoscopy showed ovarian breast carcinoma metastasis. Histopathologic examination revealed concomitant findings of leiomyoma, adenomyosis or endometrial abnormalities in 64.5% of hysterectomy specimens. CONCLUSION: Our experience with ovarian ablation either with or without hysterectomy confirmed that the use of a minimally invasive technique is feasible. We assume that ovarian ablation and hysterectomy is an appropriate treatment for premenopausal women at risk (BRCA positive) or for patients with concomitant benign uterine pathology, treated with tamoxifen in first-line therapy. Removing the uterus allows women to take only estrogens rather than combination HRT. Further investigation into the indications of disease where laparoscopic ablative surgery is appropriate in the management of early breast cancer is needed.     

A multi-institutional review of outcomes of endometrial stromal sarcoma

OBJECTIVE: To compare the clinical behavior and outcomes of low- and high-grade endometrial stromal sarcomas (LGESS and HGESS), respectively. METHODS: Patients with endometrial stromal sarcoma from five different institutions were identified and reviewed for clinicopathologic variables, surgical management and outcomes. Statistical calculations including Chi-square, t-test and survival using the Kaplan-Meier method with the log rank test were performed. RESULTS: One hundred and five patients were identified with 72 having LGESS, 31 with HGESS and 2 having unclassified tumors. The mean age was 50 years for patients with LGESS and 64 years for those with HGESS (p<0.0001). In patients with LGESS, 68% (49 patients) had disease confined to the uterine corpus or cervix compared to 39% (12 patients) in HGESS (p=0.002). The median overall survival was 53 months for HGESS and had not yet been reached in LGESS with 87.8% alive at 80 months (p<0.0001). In HGESS patients with extrauterine disease, the presence of residual disease greater than 2 cm had a significant effect on median survival. Median survival was 52 months for those who underwent optimal cytoreduction versus 2 months for those with suboptimal residual disease (p=0.007). The impact of cytoreduction was not seen in LGESS patients with extrauterine disease with 82.1% alive at 78 months. CONCLUSIONS: Low-grade and high-grade endometrial stromal sarcomas represent two distinct clinical entities and should be treated as such. Survival in patients with high-grade tumors appears to be related to amount of residual disease at the completion of initial surgery and would suggest the need for aggressive cytoreduction. The role of surgical staging and optimal adjuvant therapy remains unclear.     

Low-Grade Endometrial Stromal Sarcoma Preoperative Treatment with Depo-Lupron and Megace

A 46-year-old women presented with an inoperable low-grade endometrial stromal sarcoma. Two doses of Depo-Lupron, 7.5 mg, and Megace, 160 mg/day, were given to control uterine bleeding and shrink the tumor mass. In 9 weeks, significant reduction in the tumor occurred allowing for surgical resection. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the mainstay for primary treatment. The role of chemotherapy, radiation therapy, and hormonal therapy is poorly defined. This is a case report of neoadjuvant hormonal therapy which may improve outcomes in patients with endometrial stromal sarcomas. Additional research is needed to define the exact role of these agents.     

子宫内膜间质肉瘤术后辅助治疗方式探讨

目的探讨辅助治疗对子宫内膜间质肉瘤(ESS)复发及生存的影响。方法回顾性分析自1983-2005年于北京协和医院治疗的37例ESS的病例资料,记录人口统计学信息、诊断及治疗信息,采用SPSS11.5软件Cox回归分析进行肿瘤复发相关因素多因素分析。结果 37例患者的中位年龄为42岁(18～61岁),初次手术时有24例(64.9%)患者切除了双侧附件,术后有24例(64.9%)接受了放疗、化疗、内分泌治疗或联合的辅助治疗。中位随诊时间78个月(12～393个月),17例(45.9%)患者在随访过程中肿瘤复发,中位复发时间为122.1个月,1例患者死亡。与肿瘤复发相关的多因素分析显示手术切除双侧卵巢可显著延缓复发(P=0.001),而患者年龄、绝经状况、FIGO分期及术后是否辅助治疗对肿瘤复发无显著性影响,但初次手术后给予内分泌治疗可显著延长患者的无瘤生存期(P=0.027)。结论 ESS是一种罕见的子宫恶性肿瘤,初次手术时行双附件切除并进行适当的辅助治疗特别是内分泌治疗可显著延缓复发。     

The prognostic relevance of histological type in uterine sarcomas: a Cooperation Task Force (CTF) multivariate analysis of 249 cases

PURPOSE OF INVESTIGATION: The objective of this retrospective multicenter study was to assess the prognostic relevance of histologic type in uterine sarcomas. METHODS: The hospital reports of 249 patients with uterine sarcomas were reviewed. Surgery was the initial therapy for all patients. Histologic type was leiomyosarcoma in 95 cases, low-grade endometrial stromal sarcoma (ESS) in 19, high-grade ESS in 34, and carcinosarcoma in 101. Postoperative treatment was given without well-defined protocols. Median follow-up of survivors was 97 months. RESULTS: In the whole series 2-year, 5-year, and 10-year survival rates were 53.5%, 41.6%, and 35.8%, respectively, and median survival was 31 months. At univariate analysis survival was significantly related to stage (p = 0.0001), mitotic count (p = 0.0001), and histologic type (low-grade ESS vs leiomyosarcoma vs carcinosarcoma vs high-grade ESS, median: not reached vs 27 months vs 21 months vs 16.5 months, p = 0.0011), but not to postoperative therapy and patient age. The Cox model revealed that tumor stage, mitotic count and histologic type were independent prognostic variables for survival. In detail, the risk of death was significantly lower for low-grade ESS (risk ratio [RR] = 0.257; 95% confidence interval [CI] = 0.071-0.931) and carcinosarcoma (RR = 0.509; 955 CI = 0.324-0.799) when compared to leiomyosarcoma. Conversely, no significant difference in survival was found between leiomyosarcoma and high-grade ESS. CONCLUSIONS: Histologic type is an independent prognostic variable for survival in uterine sarcomas. Low-grade ESS has the best clinical outcome, whereas leiomyosarcoma has the poorest one. It is noteworthy that, when adjusting for stage and mitotic count, leiomyosarcoma has a significantly worse prognosis than carcinosarcoma.     

Response and survival in patients with progressive or recurrent serous ovarian tumors of low malignant potential.

OBJECTIVE: To evaluate the response to therapy and survival of patients with progressive or recurrent serous ovarian tumors of low malignant potential. METHODS: Fifty-three patients with progressive or recurrent serous ovarian tumors of low malignant potential were identified. Response was assessed and progression-free and overall survival were analyzed. The influence of clinicopathologic factors on survival was determined. RESULTS: In 49 patients with known histology of progression or recurrence, 36 (73%) had low-grade serous carcinoma, and 13 (27%) had serous ovarian tumors of low malignant potential. Forty-five patients received nonsurgical therapy and had an evaluable response. There were six (13%) patients with a complete response and six (13%) patients with a partial response. The median time to first progression or recurrence was 5.6 years. Median survival from diagnosis of first recurrence was 7.7 years. Median survival from initial diagnosis was 21 years. Nineteen (36%) patients are dead of tumor. Patients who recurred with low-grade serous carcinoma were more likely to die of tumor than those with serous ovarian tumors of low malignant potential (47% versus 0%, P =.045). Optimal cytoreduction was associated with improved survival (P =.007). CONCLUSION: Patients with progressive or recurrent serous ovarian tumors of low malignant potential have a long interval from diagnosis to progression and from progression to death, resulting in extended overall survival. Recurrence as low-grade serous carcinoma and failure to achieve optimal secondary cytoreduction were adverse prognostic factors. There were few responses to nonsurgical therapy.     

Total abdominal hysterectomy and bilateral salpingo-oophorectomy. A sufficienttreatment for patients with low risk endometrial carcinoma

Leijon T; Rosenberg P; Boeryd B. Total abdominal hysterectomy and bilateralsalpingo-oophorectomy. A sufficient treatment for patients with low riskendometrial carcinoma. Int. J. Gynecol Cancer 1997; 7:376–380.
In this prospective study, 248 surgical state I endometrial carcinomapatients with favorable prognostic factors were included. All patients weretreated only with total abdominalhysterectomy and bilateral salpingo-oophorectomy. The clinical outcome andrelapse rate were the endpoints. Only 3% of the patients recurred andthe total survival rate was96% during a median observation time of 42 months. We conclude that atotal abdominal hysterectomy and bilateral salpingo-oophorectomy is adequatetreatment for this groupof patients. In this material seven out of nine recurrences were detected byscheduled controls. Among the five patients with local recurrences, four wereasymptomatic and diagnosed during scheduled follow-up examination.     

Lack of expression of c-kit protein (CD117) in mesenchymal tumors of the uterus and ovary.

c-kit is a proto-oncogene that codes for a transmembrane tyrosine kinase receptor (CD117). The gene product KIT is constitutively overexpressed in mastocytosis and gastrointestinal stromal tumors. Recently the use of the tyrosine kinase inhibitors, such as STI-571, has resulted in the successful treatment of bcr-abl-positive leukemias and gastrointestinal stromal tumors. In gastrointestinal stromal tumors, immunostaining for c-kit is diffusely positive. Because the expression of c-kit in mesenchymal tumors of the uterus and ovary has not been previously studied, we evaluated its expression in 38 of these tumors by immunohistochemistry. The number of positive labeled/total tumors were as follows: 0/8 malignant mullerian mixed tumors, 4/7 ovarian fibrosarcomas, 0/1 clear-cell ovarian sarcoma, 0/4 uterine leiomyosarcomas, 1/10 low-grade endometrial stromal sarcomas, 0/2 high-grade endometrial stromal sarcomas, and 3/6 endometrial stromal nodules. In all positive cases, no more than 5% of the cells were labeled. In conclusion, unlike gastrointestinal stromal tumors, mesenchymal tumors of the uterus and ovary rarely express c-kit. Therefore, it is unlikely that patients with these tumors will benefit from treatment with the currently available tyrosine kinase inhibitors.     

Hysteroscopic endomyometrial resection of three uterine sarcomas.

STUDY OBJECTIVE: To describe our experience with three uterine sarcomas associated with hysteroscopic endometrial ablation. DESIGN: Cohort study (Canadian Task Force classification II-2). SETTING: University-affiliated teaching hospitals. PATIENTS: Three of 2402 women undergoing hysteroscopic endometrial ablation who had uterine sarcomas. INTERVENTION: Hysteroscopic endomyometrial resection. MEASUREMENTS AND MAIN RESULTS: One low-grade endometrial stromal sarcoma and two carcinosarcomas were resected. After hysterectomy in two patients, no residual cancer was identified in one of them. The third patient was an 82-year-old woman with moderate menorrhagia who refused hysterectomy. After endomyometrial resection she remained amenorrheic for the last 14 months of her life. CONCLUSION: From our experience the incidence of uterine sarcomas is approximately 1/800 women undergoing hysteroscopic ablation for abnormal uterine bleeding. Complete endomyometrial resection is feasible and may be offered as diagnostic and palliative therapy in women at high risk for hysterectomy.     

Anastrozole, an aromatase inhibitor, and medroxyprogesterone acetate therapy in premenopausal obese women with endometrial cancer: a report of two cases successfully treated without hysterectomy

BACKGROUND: Hormonal therapy for endometrial cancer is occasionally warranted in the premenopausal woman who is interested in maintaining fertility. Combining progesterone with an agent that eliminates the adipose production of estrogen will theoretically be more effective than progesterone alone. CASES: Two cases of reproductive-aged women with grade 1 endometrial cancer who were treated with medroxyprogesterone acetate and anastrozole daily for 3 and 6 months subsequently reverted to normal endometrium. CONCLUSION: Progesterone combined with the elimination of adipose production of estrogen may be an effective therapy in well-differentiated endometrial cancer in the obese premenopausal woman.