scholarly journals Potential Therapeutic Targets in Uterine Sarcomas

Sarcoma ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Tine Cuppens ◽  
Sandra Tuyaerts ◽  
Frédéric Amant
Keyword(s):  
Histone Deacetylases ◽  
Fusion Gene ◽  
Treatment Strategies ◽  
Endometrial Stromal Sarcoma ◽  
Mitotic Checkpoint ◽  
Uterine Sarcoma ◽  
Low Grade ◽  
Uterine Leiomyosarcoma ◽  
High Grade ◽  
Uterine Sarcomas

Uterine sarcomas are rare tumors accounting for 3,4% of all uterine cancers. Even after radical hysterectomy, most patients relapse or present with distant metastases. The very limited clinical benefit of adjuvant cytotoxic treatments is reflected by high mortality rates, emphasizing the need for new treatment strategies. This review summarizes rising potential targets in four distinct subtypes of uterine sarcomas: leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Based on clinical reports, promising approaches for uterine leiomyosarcoma patients include inhibition of VEGF and mTOR signaling, preferably in combination with other targeted or cytotoxic compounds. Currently, the only targeted therapy approved in leiomyosarcoma patients is pazopanib, a multitargeted inhibitor blocking VEGFR, PDGFR, FGFR, and c-KIT. Additionally, preclinical evidence suggests effect of the inhibition of histone deacetylases, tyrosine kinase receptors, and the mitotic checkpoint protein aurora kinase A. In low-grade endometrial stromal sarcomas, antihormonal therapies including aromatase inhibitors and progestins have proven activity. Other potential targets are PDGFR, VEGFR, and histone deacetylases. In high-grade ESS that carry the YWHAE/FAM22A/B fusion gene, the generated 14-3-3 oncoprotein is a putative target, next to c-KIT and the Wnt pathway. The observation of heterogeneity within uterine sarcoma subtypes warrants a personalized treatment approach.

scholarly journals Oral Abstract

2016 ◽  
Author(s):  
Dharma Ram
Keyword(s):  
Survival Data ◽  
Eligible Patient ◽  
Stage Iv ◽  
Endometrial Stromal Sarcoma ◽  
Uterine Sarcoma ◽  
Low Grade ◽  
Uterine Leiomyosarcoma ◽  
High Grade ◽  
Lost To Follow Up

Introduction: Uterine sarcoma accounts for nearly 3% of all uterine malignancies. They have 4 major pathology includes endometrial stromal sarcoma high grade, ESS low grade, uterine leiomyosarcoma (uLMS) and undifferentiated uterine sarcoma (UUS). Recent WHO classification 2014, recognizes low grade ESS and high grade ESS as distinct entity. They differ from endometrial carcinoma in their aggressive nature and poor prognosis. We review our database and found total 44 eligible patient treated at our institute. Materials and Methods: Its retrospective analysis of computer based database of our institute from January 2009 to December 2015. We analyzed demographic, pathological, treatment and survival data. Results: Total 44 patient treated for uterine sarcoma at our institute. Among these 16 were operated at our institute during study period. Here we reporting results of operated patients at our institute. The histological diagnosis LMS (5/16), ESS-L (4/16), MMMT (3/16), UUS (3/16) and ESS-H (1/16). Stage distribution was stage I, (6/16) stage II, (5/16) stage III, (3/16) stage IV, (0/16) and unknown stage (2/16). Two patients underwent completion surgery for outside myomectomy. The adjuvant treatment was CT in 3/16, CT with RT in 7/16, HT in 4/16 and one lost to follow up with one was put on observation. Median follow up is 30 month with 14 patients alive and one lost to follow up. At last follow up 4 patients alive with metastatic disease and 10 patients alive with no evidence of disease. Conclusion: Uterine sarcoma are uncommon disease with

Uterine Sarcomas: Histology and Its Implications on Therapy

2012 ◽  
pp. 356-361 ◽  
Author(s):  
Martee L. Hensley
Keyword(s):  
High Risk ◽  
Metastatic Disease ◽  
Objective Response ◽  
The United States ◽  
Good Prognosis ◽  
Uterine Sarcoma ◽  
Low Grade ◽  
High Grade ◽  
Limited Disease ◽  
Uterine Sarcomas

Overview: Uterine sarcomas are rare cancers, they comprise only 5% of all uterine malignancies. There are about 2,000 cases of uterine sarcoma diagnosed annually in the United States. Uterine sarcomas may be categorized as either favorable-risk, low-grade malignancies with a relatively good prognosis or as poor-risk, high-grade cancers that carry a high risk for tumor recurrence and disease progression. Expert histologic review is critical for appropriate diagnosis and management. Uterine sarcoma histologies considered to carry a more favorable prognosis include low-grade endometrial stromal sarcomas and adenosarcomas. The high-grade sarcomas include high-grade leiomyosarcomas, high-grade undifferentiated endometrial sarcomas, and adenosarcomas with sarcomatous overgrowth. The favorable histology, low-grade uterine sarcomas may be cured with surgical resection of uterus-limited disease. These tumors are often hormone-sensitive, and treatment with hormonal therapies may be efficacious for patients with advanced, unresectable disease. High-grade uterine leiomyosarcomas and undifferentiated endometrial sarcomas carry a high risk for recurrence, even after complete resection of uterus-limited disease. No adjuvant intervention has been shown to improve survival outcomes. Advanced, metastatic disease is generally treated with systemic cytotoxic therapies, which may result in objective response but is not curative. Selected patients with isolated metastatic disease and a long disease-free interval may benefit from metastatectomy.

scholarly journals Immunohistochemical panel to differentiate endometrial stromal sarcoma, uterine leiomyosarcoma and leiomyoma: something old and something new

2015 ◽  
Vol 68 (9) ◽  
pp. 710-717 ◽  
Author(s):  
Helena Hwang ◽  
Koji Matsuo ◽  
Kara Duncan ◽  
Elham Pakzamir ◽  
Huyen Q Pham ◽  
...  
Keyword(s):  
Predictive Value ◽  
Smooth Muscle Actin ◽  
Area Under The Curve ◽  
Endometrial Stromal Sarcoma ◽  
Low Grade ◽  
Uterine Leiomyosarcoma ◽  
Operating Characteristics ◽  
Uterine Sarcomas ◽  
Stromal Sarcoma ◽  
Receiver Operating Characteristics Curve

AimsTo evaluate an immunohistochemical panel differentiating endometrial stromal sarcoma (ESS) from uterine leiomyosarcoma (ULMS) and leiomyoma (LM).Methods94 cases (28 ESS, 41 ULMS, 25 LM) were retrieved and arrayed. 10 immunomarkers (estrogen receptor (ER), progesterone receptor (PR), CD10, smooth muscle actin, desmin, h-caldesmon, transgelin, GEM, ASC1, stathmin1) were used. A predictive model was constructed and examined by receiver operating characteristics curve analysis to determine area under the curve (AUC).ResultsThe combination of ER+/PR+/CD10+/GEM−/h-caldesmon−/transgelin− can predict ESS versus ULMS with AUC predictive value of 0.872 (95% CI 0.784 to 0.961, p<0.0001). The combination of ER+/PR+/CD10+/h-caldesmon−/transgelin− can predict low grade (LG) ESS from ‘LG’ ULMS with AUC predictive value of 0.914 (95% CI 0.832 to 0.995, p<0.0001). Finally, ULMS and ESS, including the LGs, were more likely to be stathmin1+ than LM.ConclusionsDue to the different clinical course and management, adding novel antibodies (GEM, transgelin) to the well established immunohistochemistry panel seemed to be useful in distinguishing ESS from ULMS and LG ESS from ‘LG’ ULMS. Finally, stathmin1 expression could be of value in differentiating LM from uterine sarcomas.

scholarly journals Laparoscopic management of endometrial stromal sarcoma in young: a case report

2020 ◽  
Vol 9 (5) ◽  
pp. 2144
Author(s):  
Shailesh Puntambekar ◽  
Shetty Theertha Shankar ◽  
Arjun Goel ◽  
Shakti Panchal
Keyword(s):  
Clinical Course ◽  
Histopathological Examination ◽  
Endometrial Stromal Sarcoma ◽  
Initial Therapy ◽  
Uterine Sarcoma ◽  
Low Grade ◽  
Lower Abdomen ◽  
Uterine Sarcomas ◽  
Stromal Sarcoma ◽  
Locally Recurrent

Endometrial stromal sarcoma (ESS) is a case malignancy and accounts for 0.2% of all uterine malignancies and 10% of all uterine sarcomas. In the present case, an unmarried 27-year-old woman presented with complaints of on and off episodes of pain in the lower abdomen. On examination, a diffuse oval mass was felt occupying the hypogastrium, iliac and lumbar regions and extending up to the umbilicus. CT scan impression was given as? Complex retroperitoneal mass? solid cystic ovarian mass with grade I right hydro nephrosis. On laparoscopy, a huge mass measuring approximately 10×10 cm was noted arising from the uterus. Laparoscopic myomectomy was done and the specimen was retrieved in a bag and the tissue was sent for histopathological examination. The postoperative clinical course was uneventful. The patient was advised to undergo oocyte cryopreservation following which she was advised hysterectomy with bilateral salphingo-oophorectomy. Pelvic radiation was advised thereafter. ESS is a rare malignant tumor, which on histopathological examination reveals sheets of cells and endometrial stromal cell differentiation. Hysterectomy with bilateral salpingo-oophorectomy is optimum initial therapy. Radiotherapy is chosen when the tumour is inadequately excised or the pelvic disease is locally recurrent. Low grade ESS is a rare form of uterine sarcoma usually seen between 40-60 years of age with limited available data regarding the clinical course and management. Early diagnosis and management is associated with a favourable prognosis and outcome.

Cytoreduction as a remedial procedure improves disease-free survival of patients with occult uterine sarcoma undergoing morcellation——a retrospective study

2020 ◽  
Author(s):  
Chao Ding ◽  
Jianqing Zhu
Keyword(s):  
Disease Free Survival ◽  
Endometrial Stromal Sarcoma ◽  
Uterine Sarcoma ◽  
Uterine Leiomyosarcoma ◽  
Uterine Sarcomas ◽  
Free Survival ◽  
Total Hysterectomy ◽  
Stromal Sarcoma ◽  
Significant Difference ◽  
Disease Free

Abstract Background：Tumor morcellation happened to facilitate iatrogenic metastasis for patients with occult uterine sarcoma. The optimal remedial procedure for these patients needed to be established. Methods：Data were retrospectively collected and analyzed from patients with occult uterine sarcoma undergoing morcellation. Results：23 consecutive patients with uterine sarcomas undergoing morcellation were accessed between Jan 2008 and Dec 2018, including 15 patients with uterine leiomyosarcoma and 8 with endometrial stromal sarcoma. Cytoreduction as a remedial procedure was significantly associated with better disease-free survival (P=0.031), and none of 7 patients undergoing cytoreduction suffered recurrence, while total hysterectomy (P=0.194) and adjuvant therapy (P=0.159) had no such benefit. There was no significant difference in disease-free survival between laparoscopic and open surgery (p=0.321). Conclusion：Cytoreduction was considered as the optimal remedial procedure for patients with occult uterine sarcoma undergoing morcellation.

scholarly journals Diagnosis and surgical therapy of uterine sarkoma

2006 ◽  
Vol 53 (3) ◽  
pp. 67-72 ◽  
Author(s):  
S. Vrzic-Petronijevic ◽  
I. Likic-Ladjevic ◽  
M. Petronijevic ◽  
R. Argirovic ◽  
N.N. Ladjevic
Keyword(s):  
Risk Factors ◽  
Survival Rate ◽  
Endometrial Stromal Sarcoma ◽  
Diagnostic Procedures ◽  
Uterine Sarcoma ◽  
Low Grade ◽  
Uterine Sarcomas ◽  
Cumulative Survival ◽  
Pathological Characteristics ◽  
Stromal Sarcoma

Introduction: Uterine sarcomas are rare gynecological neoplasms and their classification is complicated. Uterine sarcoma is usually diagnosed in postmenopausal women and the diagnosis is often accidental and postoperative. Aim of this study was to present clinical and pathological characteristics of uterine sarcomas, diagnostic procedures, treatment and two-, three- and five-years cumulative survival rates. Materials and methods: The retrospective study of 61 cases of uterine sarcomas was conducted. Cases were distributed into groups based on definitive diagnosis of uterine sarcoma: group of leiomyosarcomas (LMS), carcinosarcoma (CS), endometrial stromal sarcomas (ESS), adenosarcomas (AS) and other rare uterine sarcomas. We investigated patients with clinical and pathological characteristics of uterine sarcomas, diagnostic procedures and treatment. Survival rate was calculated by Kaplan-Meier method. Results: From 61 patients 43 patients (70.49%) were postmenopausal. Mean period from menopause until appearance of symptoms was 14,63 years. One or more risk factors were present in 46 (75.4%) patients. Diagnosis of uterine sarcoma were established averagely 7.38 months after appearance of symptoms. 50 patients (82.0%) underwent one or more diagnostic procedures. Preoperative diagnosis of uterine sarcoma was established in 42.5% of patients. 53 (86.9%) of patients were treated operatively. The most used operative procedure (60,7%) was total hysterectomy with bilateral salpingooophorectomy. Postoperative pathohistologic analysis showed that low grade (LG) leiomyosarcoma were present in 19 (35.9%) cases, high grade (HG) leiomyosarcoma in 1 (1.9%) case, carcinosarcoma in 14 (26.4%) cases, low grade (LG) endometrial stromal sarcoma in 5 (9.4%) cases, high grade (HG) endometrial stromal sarcoma in 9 (17.0%) cases, adenosarcoma in 2 (3.8%) cases, and 2 cases of rare uterine sarcomas: 1 (1.9%) MALT HG lymphoma and 1(1.9%) malignant hemangiopericytoma. In one case of ESS (1.9%) only adenomyosis was found postoperatively suggesting that the whole tumour was removed during diagnostic procedure. Eight patients were not treated operatively. Two-years cumulative survival rate was 74.3%, three-years cumulative survival rate was 71.1%, and five years survival rate was 64.3%. Discussion: Average age, percent of postmenopausal patients and the mean age at the time of menopause in our studied correlate with current data. Clinical presentation of uterine sarcoma is associated with obesity and hypertension in more than 30% of cases, which is approved in our study. For early diagnostics it is important to notice that risk factors are similar to those connected with far more frequent endometrial carcinoma. Postmenopausal abnormal bleeding was the main reason for medical examination, explaining relatively short period for establishing the diagnosis in this group of patients. The variety of clinical findings in our studied group showed that the diagnosis must be based on preoperative pathohistology. Conclusion: Adequate diagnosis and treatment of uterine sarcoma is possible with regular yearly or more frequent follow-up, especially in postmenopausal women with known risk factors present. We need special attention for unclear symptoms and postmenopausal bleeding and we need to use all diagnostic procedures soon as possible including preoperative histology because early metastases are characteristic for uterine sarcomas. Factor of the most important predictive value is histologic grade. .

scholarly journals Omentectomy in Combination With Hysterectomy As a Remedial Procedure Improves Disease-Free Survival of Patients With Occult Uterine Sarcoma Undergoing Morcellation: A Retrospective Study

2021 ◽  
Author(s):  
Chao Ding ◽  
Jianqing Zhu
Keyword(s):  
Open Surgery ◽  
Disease Free Survival ◽  
Endometrial Stromal Sarcoma ◽  
Uterine Sarcoma ◽  
Uterine Leiomyosarcoma ◽  
Uterine Sarcomas ◽  
Free Survival ◽  
Stromal Sarcoma ◽  
Significant Difference ◽  
Disease Free

Abstract Background：Tumor morcellation happened to facilitate iatrogenic metastasis for patients with occult uterine sarcoma. The optimal remedial procedure for these patients needed to be established. Methods：Data were retrospectively collected and analyzed from patients with occult uterine sarcoma undergoing morcellation. Results：23 consecutive patients with uterine sarcomas undergoing morcellation were accessed between Jan 2008 and Dec 2018, including 15 patients with uterine leiomyosarcoma and 8 with endometrial stromal sarcoma. Hysterectomy + omentectomy as a remedial procedure was significantly associated with better disease-free survival (P=0.031), and all 7 patients undergoing the previous procedure remain disease free. However, nether simple hysterectomy (P=0.194) nor adjuvant therapy (P=0.159) had such benefits. There was no significant difference in disease-free survival between laparoscopic and open surgery (p=0.321). Conclusion：Hysterectomy + omentectomy was considered as the optimal remedial procedure for patients with occult uterine sarcoma undergoing morcellation.

Clinical Outcome of ET-743 (Trabectedin; Yondelis) in High-Grade Uterine Sarcomas: Report on Five Patients and a Review of the Literature

2009 ◽  
Vol 19 (2) ◽  
pp. 245-248 ◽  
Author(s):  
Frédéric Amant ◽  
An Coosemans ◽  
Vincent Renard ◽  
Els Everaert ◽  
Ignace Vergote
Keyword(s):  
Clinical Benefit ◽  
Response Rate ◽  
Uterine Sarcoma ◽  
Current Data ◽  
Clinical Impact ◽  
High Grade ◽  
Review Of The Literature ◽  
Uterine Sarcomas ◽  
Previously Treated ◽  
Undifferentiated Uterine Sarcoma

AbstractThe clinical impact of ET-743 (trabectedin; Yondelis) in women with leiomyosarcoma and undifferentiated uterine sarcoma in patients previously treated with chemotherapy is investigated. Current data show a clinical benefit in 2/5 patients, of which 1 had a partial remission during 9 months. Pooling the treatment outcomes with literature data, a response in 5 (38%) of 13 patients and a clinical benefit in 7 (54%) of 13 patients for all high-grade uterine sarcomas is calculated. When only uterine leiomyosarcomas are concerned, response rate is 5 (45%) of 11 patients with a clinical benefit in 7 (64%) of 11 patients. These results on the use of ET-743 in uterine sarcoma patients support the conductance of larger trials.

scholarly journals Isobolographic Analysis Demonstrates the Additive and Synergistic Effects of Gemcitabine Combined with Fucoidan in Uterine Sarcomas and Carcinosarcoma Cells

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 107 ◽  
Author(s):  
Marcin Bobiński ◽  
Karolina Okła ◽  
Jarogniew Łuszczki ◽  
Wiesława Bednarek ◽  
Anna Wawruszak ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Synergistic Effect ◽  
Cell Line ◽  
Cell Lines ◽  
Combined Treatment ◽  
Endometrial Stromal Sarcoma ◽  
Uterine Leiomyosarcoma ◽  
Uterine Sarcomas ◽  
Isobolographic Analysis ◽  
Stromal Sarcoma

Background: Uterine sarcomas and carcinosarcoma are associated with unfavorable prognosis. The regimens that are used in chemotherapy are associated with high incidence of side effects and usually do not significantly increase patients’ survival rates. In this study we investigated the activity and interactions between gemcitabine and fucoidan, the natural compound known for its anti-tumor properties, in human sarcomas and carcinosarcoma cell models. Methods: SK-UT-1, SK-UT1-B (carcinosarcoma), MES-SA (leiomyosarcoma), and ESS-1 (endometrial stromal sarcoma) cell lines were used for the experiments. Cells were incubated in the presence of gemcitabine, fucoidan, and mixtures, after the incubation the MTT tests were performed. In order to assess the interactions between tested compounds isobolographic analysis was performed. Additional assessments of apoptosis and cell cycle were done. Results: Additive effect of combined treatment with gemcitabine and fucoidan was observed in ESS-1 and SK-UT-1 cell line. Although the supra-additive (synergistic) effect noticed in SK-UT-1B cell line. It was not possible to determine the interactions of fucoidan and gemcitabine in MES-SA cell line due to insufficient response to treatment. Addition of fucoidan to gemcitabine enhances its proapoptotic activity, what was observed especially in ESS-1 and SK-UT-1B cell lines. The arrest of cell cycle induced by mixture of gemcitabine and fucoidan, superior comparing gemcitabine alone was observed in SK-UT-1B. Conclusions: Obtained data showed that a combination of fucoidan and gemcitabine in uterine endometrial stromal sarcoma and carcinosarcoma cell lines has additive or even synergistic effect in decreasing cell viability. Furthermore, this drug combination induces apoptosis and arrest of cell cycle. The resistance of uterine leiomyosarcoma cell line, justifies searching for other drugs combinations to improve therapy efficacy.

Sign in / Sign up

Export Citation Format

Share Document