scholarly journals DNA-cytometric characteristics of recurrent soft tissue sarcomas

2018 ◽  
Vol 99 (3) ◽  
pp. 415-420
Author(s):  
E M Nepomnyashchaya ◽  
E P Ul'yanova ◽  
I A Novikova ◽  
O N Selyutina ◽  
E Yu Zlatnik ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Tumor Grade ◽  
Cell Loss ◽  
Biological Potential ◽  
M Phase ◽  
Poorly Differentiated ◽  
G0 Phase ◽  
Well Differentiated

Aim. To determine the content of deoxyribonucleic acid (DNA) and distribution of cells in mitotic phases in patients with recurrent soft tissue sarcomas for the assessment of malignancy of the process. Methods. Tumor tissues of patients with recurrent soft tissue sarcomas were studied. Research methods included histological, DNA-cytometric and statistical methods. Results. Proliferative activity and proliferative index of recurrent sarcomas differed depending on the tumor grade and stage. Differences in the number of diploid, aneuploid and polyploid cells were determined in each group and between the groups depending on the cell cycle phases. Cell cycle parameters were as following: 100% of G1 (well-differentiated) cancer were diploid, as well as 33.3% of G2 (moderately differentiated) and 15% of G3 (poorly differentiated) tumors. Aneuploid tumors prevailed in G2 and G3, the ratio of which was 66.7 and 85%, respectively. The analysis of kinetic parameters of the cell cycle allowed establishing a decrease in the number of cells in G1/G0 phase of the cell cycle from G1 to G3, which was accompanied by a statistically significant increase in the proportion of cells in S-phase (p ˂0.05). Conclusion. The DNA-cytometric study of cell cycle parameters showed high biological potential of recurrent soft tissue sarcomas, which was determined by two indices - the proportion of cells in G2+M-phase and the cell loss factor; 100% of well-differentiated (G1) tumors, 33.3% of moderately differentiated (G2) and 15% of poorly differentiated (G3) tumors were diploid; aneuploid tumors prevailed in G2 and G3.

Comparative DNA cytometry of primary and recurrent soft tissue sarcomas.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e22516-e22516
Author(s):  
Irina Dashkova ◽  
Larisa N. Vashchenko ◽  
Oleg Ivanovich Kit ◽  
Inna A. Novikova ◽  
Ekaterina Komarova ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Soft Tissue ◽  
Dna Content ◽  
Soft Tissue Sarcomas ◽  
Literary Analysis ◽  
Proliferation Index ◽  
Cell Distribution ◽  
Dna Cytometry ◽  
Flow Cytofluorometry ◽  
M Phase

e22516 Background: Soft tissue sarcomas (STS) are aggressive tumors with a high degree of recurrence. Radical resection within healthy tissues allows to reduce the recurrence percentage to 25-30% without subsequent therapy. The literary analysis has shown that the study of various biological properties of primary and recurrentsoft tissue tumorsis being conducted. However, currently there is a lack of information to understand the reasons for STS recurrence. The goal of investigation was to reveal the distinctive features of the DNA content and cell distribution in the phases of the cell cycle of recurrent STS. Methods: DNA cytometry in the tumor tissue of 30 primary soft tissue sarcomas and 30 STS recurrences was carried out using the method of flow cytofluorometry. The tumor ploidy and cell distribution in the cell cycle phases were analyzed. Results: A number of differences in the DNA cytometric parameters of primary and recurrent STS have been revealed, they include: an increase in the proportion of aneuploid tumors in case of recurrence, the number of tumors with DNA index within the mitotic cycle, an increase in the proportion of cells in G2+M- phase of diploid and aneuploid tumors and a decrease in S- phase of aneuploid ones. It has been shown that with a G2 differentiation degree, the proportion of cells in G2+M, S- and proliferation index of recurrent STS is significantly lower than the primary parameters. An increase in the proportion of cells in G2+M- phase and a decrease in the rate of proliferation of recurrent STS, depending on the stage, are shown only in case of stage III. Conclusions: The revealed features of DNA content and cell cycle of tumor cells of soft tissue sarcomas will allow to approach to understanding of biological bases of recurrence of this malignant disease.

Altered Expression of G1 Regulatory Proteins in Human Soft Tissue Sarcomas

2002 ◽  
Vol 126 (5) ◽  
pp. 567-573 ◽  
Author(s):  
Jinyoung Yoo ◽  
Sonya Y. Park ◽  
Seok Jin Kang ◽  
Sang In Shim ◽  
Byung Kee Kim
Keyword(s):  
Cell Cycle ◽  
Soft Tissue ◽  
Cyclin D1 ◽  
Soft Tissue Sarcomas ◽  
Tumor Grade ◽  
Regulatory Proteins ◽  
Nuclear Accumulation ◽  
Cyclin D ◽  
P53 Pathway ◽  
Altered Expression

Abstract Context.—Soft tissue sarcomas constitute a heterogeneous group of tumors for which tumorigenesis is not fully understood. Altered cell-cycle regulation may underlie the development and/or progression of human malignancies. However, data concerning the occurrence of cell-cycle aberrations in soft tissue sarcomas are very limited. Objectives.—To detect the abnormal features of cell-cycle regulatory proteins in soft tissue sarcomas and to determine the potential role of these proteins in clinical behavior. Design.—The p53 and Rb–cyclin D pathways were investigated by immunohistochemical studies of p53, mdm2, pRb, p16, cyclin D1, and cdk4 proteins, respectively. Results.—Of the 67 sarcomas analyzed, nuclear accumulation of p53 was detected in 25 samples (37%), and overexpression of mdm2 was found in 16 samples (24%). Both p53 and mdm2 expression correlated with tumor grade. Abnormalities involving the Rb–cyclin D pathway were identified in all of the tumors by the altered expression of either pRb (72%) or p16 (94%). Fourteen (21%) and 64 (96%) cases demonstrated cyclin D1 or cdk4 expression, respectively. Overexpression of cyclin D1 showed an association with pRb and p53. There was no correlation between pRb, p16, cyclin D1, or cdk4 and tumor grade or relapse. Conclusion.—Disturbance in the cell-cycle regulatory system involving the p53 pathway and the Rb–cyclin D pathway is relatively frequent in soft tissue sarcomas and may be a contributing factor in the tumorigenesis of these tumors. The alterations in the Rb–cyclin D pathway probably constitute an early event, whereas the abnormalities in the p53 pathway seem to be involved in tumor progression. It is noteworthy that cyclin D1 may play a key role in linking both pathways.

Comparative analysis of cell cycle parameters in primary and recurrent soft tissue sarcomas.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e22538-e22538
Author(s):  
Inna Arnoldovna Novikova ◽  
Evgeniya M. Nepomnyashchaya ◽  
Timur Aliev ◽  
Elena Yurievna Zlatnik ◽  
Olesya N. Selyutina ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Comparative Analysis ◽  
Soft Tissue ◽  
Dna Content ◽  
Soft Tissue Sarcomas ◽  
Disease Stage ◽  
Primary Tumors ◽  
Recurrent Tumors ◽  
M Phase

e22538 Background: The purpose of the study was to determine DNA content and distribution of cells in cell cycle phases by flow cytometry in patients with primary and recurrent soft tissue sarcomas. Methods: 60 patients with soft tissue sarcomas (STS) were recruited: 30 with primary tumors and 30 with recurrent ones. Mean age of patients with primary STS was 56±5.4 years, with recurrent STS – 55±6.7 years. DNA content was determined using the BD Facs Cantoo II flow cytometer with CycleTEST PLUS DNA Reagent Kit (Becton Dickinson). The data were processed using ModFit LT program. Results: Comparative analysis of the cell cycle kinetics showed an increase in the percentage of cells in G2+M phase by 2 times in diploid and by 2.1 times in aneuploid recurrent tumors in comparison with primary ones (1.8±0.5% vs. 0.9±0.1% for diploid tumors; 5.4±2.2% vs. 2.6±0.7% for aneuploid tumors). An increase in the percentage of aneuploid tumors was found in recurrent G2 and G3 tumors (from 50% in primary to 66.7% in recurrent G2 tumors and from 63.25% in primary to 85% in recurrent G3 tumors). Mean content of aneuploid cells in recurrent G2 tumors was 2.2 times higher (p≤0.05), while the differences in primary and recurrent G3 tumors were not significant. The percentage of aneuploid tumors depended on the disease stage and increased in stages IIb and III in recurrent tumors, compared to primary ones (from 37.5% to 71.4% in recurrent st. IIb; and from 65% in primary st. III to 72.7% in recurrences) (p≤0.05). Conclusions: DNA analysis by flow cytometry demonstrated a high biologic potential of both primary and recurrent tumors. Some values in the mitotic cycle in recurrent tumors were probably associated with adjuvant therapy, as well as influenced by the coefficient of two parameters – the percentage of cells in G2+M phase and the cell loss factor determining a high malignant potential of these tumors.

scholarly journals Retroperitoneal Liposarcoma Presenting as Bilateral Inguinal Hernias

2021 ◽  
Author(s):  
DO Haley S. Lehman ◽  
DO Ryan N. Qasawa ◽  
John J. Lim
Keyword(s):  
Case Report ◽  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Mass Effect ◽  
Potential Space ◽  
Retroperitoneal Liposarcoma ◽  
Median Size ◽  
Inguinal Hernias ◽  
Retroperitoneal Tumors ◽  
Well Differentiated

Abstract Liposarcoma is one of the most common soft tissue sarcomas and has multiple subtypes, including atypical, well-differentiated, and dedifferentiated liposarcoma1. These tumors most commonly occur in the extremities and the retroperitoneum2, and account for 20% of all retroperitoneal tumors3. Retroperitoneal liposarcoma is very rare overall, occurring in 2.5 per one million people4. Patients will present from symptoms of mass effect due to the uncontrolled growth in the large potential space of the retroperitoneum, with its median size being around 30 cm5. The mainstay of treatment for this type of tumor is resection to a negative margin6. This is a case report describing a retroperitoneal liposarcoma presenting with bilateral inguinal hernias containing intraperitoneal fat from mass effect.

scholarly journals Well-Differentiated Liposarcoma of The Larynx: A Case Report and Review of Literature

2016 ◽  
Vol 9 (1) ◽  
pp. 85-89
Author(s):  
Svetlana A. Mateva ◽  
Margarita R. Nikolova ◽  
Alexandar V. Valkov ◽  
Margarita R. Nikolova
Keyword(s):  
Case Report ◽  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
World Health ◽  
Low Grade ◽  
Review Of Literature ◽  
Grade Malignancy ◽  
Well Differentiated ◽  
Health Organization ◽  
Histologic Types

Summary Liposarcoma is one of the most common soft tissue sarcomas in adults with a relative incidence amongst other sarcomas ranging from 9.8% to 16%. It usually locates in the limbs and retroperitoneum. Primary liposarcomas of the larynx and hypopharynx are rare, comprising less than 20% of all head and neck liposarcomas. According to World Health Organization, these tumors are divided into four histologic types, and well-differentiated liposarcoma is the most common one. It is a tumor of low-grade malignancy that may recur locally, but does not metastasize. We present a case of laryngopharyngeal well- differentiated liposarcoma in an old patient with two previous removals. We also discuss recently published cases with this unusual location of liposarcoma.

Rechallenge with trabectedin in patients with locally advanced or metastatic soft tissue sarcoma following drug holiday: The experience of the French Sarcoma Group (FSG).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10062-10062 ◽  
Author(s):  
Esma Saada ◽  
Chahineze Rahal ◽  
Isabelle Ray Coquard ◽  
Antoine Italiano ◽  
Christine Chevreau ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Objective Response ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Myxoid Liposarcoma ◽  
Median Number ◽  
Drug Holiday ◽  
Who Grade ◽  
Well Differentiated ◽  
Number Of Cycles

10062 Background: Trabectedin (T) is a marine-derived alkaloid used to treat advanced soft tissue sarcomas (STS) after ifosfamide and/or anthracyclins failure. Since then, the FSG evaluated the clinical benefit in re-administrating T after an initial hold, either medically indicated or upon patient’s request. Methods: Following an online request, clinical and histopathological data were collected from six centers of the FSG who declared to have rechallenged patients. Baseline data were collected and analyze will be used. Results: From 1999 to 2011, 49 pts with T drug holiday have been identified (26 male/ 23 female), with a median age of 50 y [23-75]. Most frequent histotypes were: myxoid liposarcoma (18, 36.7%), leiomyosarcomas (13, 26.5 %) and well-differentiated/dedifferentiated liposarcoma (9, 18%). WHO grade were 1 in 14 (29%), 2 in 19 (39%) and 3 in 5 (10%) pts respectively. Patients who had a maximum of 2, 3 or 4 therapeutic sequences (TS) with T (drug-holiday and rechallenge) were 41/49 ,7/49 and 1/49 respectively. Median number of cycles for 1, 2, 3 and 4 TS were 7 [3-21], 6 [2-30], 6 [2-9] and 6. Median total number of cycles was 15 [6-43]. Median duration of drug-holiday for 1, 2 and 3 TS were 11 [3-91], 7 [2-29] and 4 months [1-5]. Grade 3-4 toxicities incidence decreased with the number of TS (occurred in 36%, 29%, 14% and 0% of pts with 1, 2, 3 and 4 TS) as well as mean T dose per cycle (1.3 mg/m², 1.2 mg/m², 1.1 mg/m² and 1.1 mg/m² for TS 1, 2, 3, 4). Efficacy decreased with number of TS (Number of CR/PR/SD/PD were 1 (2%)/15 (31%)/33 (67%)/0 for TS1; 0/4 (8%)/29 (59%)/16 (3%) for TS2; 0/1 (14%)/2 (29%)/4 (57%) for TS3 and 0/0/0/1(100%) for TS4). Median overall survival was 5.0 y [2.7-7.3] since T introduction, and 1.5 y [0.1-4.8], 0.8 y [0.5-1.3] and 0.6 y following 2nd, 3rd and 4th T reintroduction respectively. Objective response after TS2 were seen in 4 cases of grade 1 sarcomas. Conclusions: Due to the lack of cumulative toxicities over time with T, its rechallenging in responding patients to T (no progression under T) have to be considered in advanced STS.

scholarly journals Prognostic Factors in Extremity Soft Tissue Sarcoma Patients Treated with Preoperative Radiotherapy

2019 ◽  
Vol 4 (03) ◽  
Author(s):  
Berrin Inanc, MD ◽  
Kubilay Inanc, MD
Keyword(s):  
Prognostic Factors ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Preoperative Radiotherapy ◽  
Soft Tissue Sarcomas ◽  
Tumor Grade ◽  
Metastatic Recurrence ◽  
Extremity Soft Tissue Sarcoma ◽  
Metastatic Relapse

Purpose: The purpose of the study was to investigate the prognostic factors and survival after preoperative radiotherapy in Extremity Soft Tissue Sarcomas (ESTS). Materials and Methods: In this retrospective study, all patients treated for an extremity sarcoma with pre-operative radiotherapy followed by surgery. Results: The mean follow-up for all 24 ESTS patients was 15.5 (range: 10-39 months). At last follow-up, 9 patients (37%) were alive, 15 patients (62%) had died of distant disease progression. Among the patients died, there were 15 with metastatic relapse (13 lung and 2 cranial metastasis), 5 with both local and metastatic recurrence. The median OS was 16 month. The 2-years actuarial OS rate and 3-years OS rate were 39% and 26%, respectively. The median RFS was 14(12.5-15.4) month. The 2-years and 3-years RFS rate was 71%.The median MFS was 12 months. The 2-years and 3-years MFS rate were 33%, 17%, respectively. The effects of age, sex, histopathologic type, tumor size, tumor localization, tumor grade, tumor depth, radiation doses and recestion margin on OS, RFS, MFS were not observed. In univariate and multivariate model, it was observed that recurrence decreased OS time significantly (p<0.05). Conclusion: Recurrens and metastasis are strong and negative prognostic factor for survival in extremity soft tissue sarcoma patients.

scholarly journals Recurrent DMD Deletions Highlight Specific Role of Dp71 Isoform in Soft-Tissue Sarcomas

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 922 ◽  
Author(s):  
Olivier Mauduit ◽  
Vanessa Delcroix ◽  
Tom Lesluyes ◽  
Gaëlle Pérot ◽  
Pauline Lagarde ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Soft Tissue Sarcomas ◽  
Metastatic Progression ◽  
Gene Encoding ◽  
M Phase ◽  
Synovial Sarcomas ◽  
Dmd Gene

Soft-tissue sarcomas (STS) are rare tumors whose oncogenesis remains unknown and for which no common therapeutic target has yet been identified. Analysis of 318 STS by CGH array evidenced a frequent deletion affecting the DMD gene (encoding dystrophin isoforms) in 16.5% of STS, including sarcomas with complex genomics, gastrointestinal tumors (GIST), and synovial sarcomas (SS). These deletions are significantly associated with metastatic progression, thus suggesting the role of DMD downregulation in the acquisition of aggressive phenotypes. We observed that targeted deletions of DMD were restricted to the 5’ region of the gene, which is responsible for the transcription of Dp427. Analysis of STS tumors and cell lines by RNA sequencing revealed that only the Dp71 isoform was widely expressed. Dp427 depletion had no effect on cell growth or migration. However, Dp71 inhibition by shRNA dramatically reduced the cell proliferation and clonogenicity of three STS cell lines, likely by altering the cell cycle progression through the G2/M-phase. Our work demonstrates that DMD deletions are not restricted to myogenic tumors and could be used as a biomarker for metastatic evolution in STS. Dp71 seems to play an essential role in tumor growth, thus providing a potential target for future STS treatments.

Leiomyosarcoma of the urinary bladder: a clinicopathological study of 34 cases

2010 ◽  
Vol 63 (8) ◽  
pp. 708-713 ◽  
Author(s):  
Matthew R Lindberg ◽  
Cyril Fisher ◽  
Khin Thway ◽  
Dengfeng Cao ◽  
John C Cheville ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Adverse Outcome ◽  
Soft Tissue Sarcomas ◽  
Mitotic Rate ◽  
Low Grade ◽  
Grading Systems ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Degree Of Differentiation

BackgroundLeiomyosarcomas of the urinary bladder (LMS-UB) are rare, usually aggressive neoplasms. Owing to their rarity, only a limited number of cases with clinical follow-up information have been published. There is no current consensus on LMS-UB grading, and it is unknown whether the widely accepted Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) and National Cancer Institute (NCI) grading systems of soft-tissue sarcomas are applicable to LMS-UB.MethodsThe authors studied 34 well-characterised LMS-UB and compared the prognostic power of the FNCLCC and NCI systems with that of one published grading scheme for LMS-UB (Mayo). All available slides from 34 LMS-UB were retrieved and evaluated with regards to degree of differentiation, mitotic rate/10 high-powered fields (HPF), and % necrosis. Cases were graded using published criteria for the FNCLCC, NCI and Mayo schemes. Follow-up information was obtained.ResultsThe tumours occurred in 17 females and 17 males, ranging from 31 to 91 years (median 65), and measured 2–12 cm in size. One tumour was well differentiated, 17 tumours were moderately differentiated, and 16 tumours were poorly differentiated. Mitotic rates ranged from 1 to >30/10 HPF (median 12/10 HPF), and tumours showed 0–60% necrosis (median 25%). FNCLCC grades were 1 (3), 2 (12) and 3 (19). NCI grades were 1 (2), 2 (11) and 3 (21). Mayo grades were low (7) and high (27). FNCLCC and NCI grades were identical in 23/34 cases (68%). Four cases were FNCLCC/NCI grade 2 or 3 and Mayo low-grade. Clinical follow-up was available for 25 of 34 patients (74%). Clinical follow-up of ≥12 months was available for 17 of these 25 cases (68%) with a median follow-up duration of 52 months (range 12–120 months). Adverse outcome was seen in nine of these 17 patients (53%). Seven of the eight cases (88%) with a clinical follow-up duration of <12 months died of their disease. Overall, adverse outcome was documented in 16 of 25 (64%) cases. Metastatic disease was seen in 13 of 25 (52%) cases, with the lungs being the most common site of metastasis (62%). Adverse outcome was noted in 15 of 23 (65%) of FNCLCC grade 2 or 3 LMS-UB, as compared with zero of two (0%) FNCLCC grade 1 tumours (p=0.15), in 15 of 23 (65%) NCI grade 2 or 3 LMS-UB, versus zero of two (0%) NCI grade 1 sarcomas (p=0.17) and in 13 of 20 (65%) Mayo high grade LMS-UB, as opposed to two of five (40%) low-grade lesions (all results not statistically significant).ConclusionsThe authors conclude that LMS-UB occurs in older adults of either sex and is characterised by aggressive behaviour, with adverse outcome in >60% of cases. Certain advantages of the FNCLCC system may support its more widespread adoption for future studies.

Epithelioid Hyalinizing Sarcoma With MGA-NUTM1 Fusion

2020 ◽  
Vol 154 (6) ◽  
pp. 859-866
Author(s):  
Caroline I M Underwood ◽  
Diana M Cardona ◽  
Rex C Bentley ◽  
Guomiao Shen ◽  
Xiaojun Feng ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Immunohistochemical Study ◽  
Soft Tissue Sarcomas ◽  
Soft Tissue Tumors ◽  
Molecular Testing ◽  
Molecular Alterations ◽  
Poorly Differentiated ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Objectives Soft tissue sarcomas are a group of tumors derived from the mesenchymal origin. Historically, they have been classified according to morphologic and immunohistochemical characteristics. The advent of multiplexed next-generation sequencing (NGS), specifically RNA sequencing, has modified the classification of such tumors and others by determining categorization based on molecular alterations. The NUTM1 rearrangement, previously thought to be present only in carcinomas, has recently been reported in poorly differentiated high-grade sarcomas of the soft tissue. We present the first reported case of an epithelioid hyalinizing sarcoma harboring the MGA-NUTM1 fusion in an acral site. Methods Histopathologic, immunohistochemical, and molecular testing were performed on resection tissue. Results Histologically, the tumor showed an epithelioid morphology with prominent background hyalinization. Immunohistochemically, the tumor expressed CD99 and nuclear NUT-1. By NGS the tumor harbors MGA-NUTM1 fusion. Conclusions Our findings support more extensive use of NGS for accurate sarcoma classification and identification of potential therapeutic targets. Furthermore, they corroborate the fact that NUTM1-rearranged soft tissue tumors represent a spectrum of heterogeneous morphologic entities. This case also highlights the utility of NUT-1 immunohistochemical study as a possible screening tool for NUTM1-fused sarcomas.

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