scholarly journals Expression Patterns of TOP2A and SIRT1 Are Predictive of Survival in Patients with High-Risk Soft Tissue Sarcomas Treated with a Neoadjuvant Anthracycline-Based Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4877
Author(s):  
Luc M. Berclaz ◽  
Annelore Altendorf-Hofmann ◽  
Hans Roland Dürr ◽  
Alexander Klein ◽  
Martin K. Angele ◽  
...  
Keyword(s):  
High Risk ◽  
Soft Tissue ◽  
Expression Patterns ◽  
Soft Tissue Sarcomas ◽  
Tissue Microarrays ◽  
Clinicopathological Parameters ◽  
Predictors Of Response ◽  
Significant Prolongation ◽  
Response To Chemotherapy ◽  
Pre Treatment

Molecular predictors of response to chemotherapy and survival have not been put into clinical practice in high-risk soft tissue sarcomas (HR-STS) by now. The expression of TOP2A and SIRT1 has implications for the mechanism of action of doxorubicin, which is the backbone of chemotherapy in HR-STS. Pre-treatment samples of 167 patients with HR-STS were collected. Protein expression levels of TOP2A and SIRT1 were evaluated with tissue microarrays and immunohistochemistry and correlated with clinicopathological parameters, including overall survival (OS). The expression of TOP2A and SIRT1 was seen in 47% and 60% of patients with HR-STS, respectively. TOP2A expression was associated with higher tumor grading and shorter 5-year OS. The expression of SIRT1 was correlated with a better 5- and 10-year OS. The combination of high SIRT1 and low TOP2A (“Top survivors”) significantly predicted a better OS compared to other biomarker combinations. A multivariate analysis confirmed the expression of SIRT1 and the “Top survivor” biomarker combination as independent predictive factors of OS. This is the first study to associate SIRT1 overexpression with a statistically significant prolongation of OS in HR-STS. Both individual markers and their combination can be used as predictive indicators for HR-STS patients scheduled for neoadjuvant anthracycline-based chemotherapy.

scholarly journals Cancer Testis Antigens and Immunotherapy: Expression of PRAME Is Associated with Prognosis in Soft Tissue Sarcoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3612
Author(s):  
Markus Albertsmeier ◽  
Annelore Altendorf-Hofmann ◽  
Lars H. Lindner ◽  
Rolf D. Issels ◽  
Eric Kampmann ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Expression Patterns ◽  
Soft Tissue Sarcomas ◽  
Clinicopathological Parameters ◽  
Lower Grade ◽  
Term Survival ◽  
Expression Levels ◽  
Cancer Testis Antigens ◽  
Cellular Immune ◽  
Cancer Testis

(1) Background: PRAME, NY-ESO-1, and SSX2 are cancer testis antigens (CTAs), which are expressed in testicular germ cells with re-expression in numerous cancer types. Their ability to elicit humoral and cellular immune responses have rendered them promising targets for cancer immunotherapy, but they have never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: On a protein level, we examined PRAME, NY-ESO-1, and SSX2 expression in tumour tissues of 249 high-risk STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including tumour-infiltrating lymphocyte (TIL) counts, grading, and long-term survival. (3) Results: Expression of PRAME, NY-ESO-1, and SSX2 was observed in 25 (10%), 19 (8%), and 11 (4%) of 249 specimens with distinct patterns for histo-subtypes. Expression of PRAME was associated with shorter patient survival (p = 0.005) and higher grade (G2 vs. G3, p = 0.001), while NY-ESO-1 expression was correlated with more favourable survival (p = 0.037) and lower grade (G2 vs. G3, p = 0.029). Both PRAME and NY-ESO-1 expression were more frequent in STS with low TIL counts. In multivariate analysis, high PRAME and low SSX2 expression levels as well as metastatic disease and non-radical resections were independent predictors of shorter overall survival. (4) Conclusions: CTAs PRAME, NY-ESO-1, and SSX2 show distinct expression patterns in different STS subtypes. These results demonstrate their prognostic relevance and may guide future immunotherapeutic approaches in STS.

scholarly journals Expression patterns of PD-L1 and PD-1 provide rationales for immune checkpoint inhibition in soft tissue sarcomas

2019 ◽  
Author(s):  
Martin F. Orth ◽  
Veit L. Buecklein ◽  
Eric Kampmann ◽  
Marion Subklewe ◽  
Elfriede Noessner ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Clinical Outcome ◽  
Immune Checkpoint ◽  
Expression Patterns ◽  
Soft Tissue Sarcomas ◽  
Clinicopathological Parameters ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Anti Cancer ◽  
Expression Status

ABSTRACTSoft tissue sarcomas (STS) are highly malignant cancers with mesenchymal origin. In many instances, clinical outcome is poor due to high rates of local recurrence and metastasis.The programmed death receptor ligand 1 (PD-L1) is expressed in several cancers. PD-L1 interacts with its receptor, PD-1, on the surface of tumor infiltrating lymphocytes (TILs), thereby attenuating anti-cancer immune response. Immune checkpoint inhibitors targeting this interaction are promising new anti-cancer drugs. However, present studies on the PD-L1 and PD-1 expression status in STS are limited either by small sample size, analysis of single STS subtypes, or lack of combinatorial assessment of PD-L1, PD-1 and TILs.To overcome these limitations, we evaluated the expression patterns of intratumoral PD-L1, the amount of TILs and their PD-1 expression status, as well as associations with clinicopathological parameters in a large and comprehensive cohort of 274 samples comprising more than six STS subtypes.We found that nearly all STS subtypes showed partial PD-L1 expression, albeit with a broad range of PD-L1 positivity across subtypes (50% angiosarcomas, 23% UPS, 13% leiomyosarcomas, 12% dedifferentiated liposarcomas, 3% synovial sarcomas, 0 MPNST, and 18% mixed sarcomas). Co-expression and correlation analyses uncovered that expression of PD-L1 was associated with more PD-1 positive TILs (P< 0.001), higher tumor grading (P= 0.022) and worse patients’ 5-year overall survival (P= 0.016).In sum, the substantial portion of STS showing PD-L1 expression, the simultaneous presence of PD-1 positive TILs, and the association of PD-L1 with unfavorable clinical outcome provide a rationale for immune checkpoint inhibition in patients with PD-L1-positive STS.

scholarly journals High Prevalence of 5T4/Trophoblast Glycoprotein in Soft Tissue Sarcomas

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4841
Author(s):  
Patrick Groothuis ◽  
Nicola Penel ◽  
Antoine Italiano ◽  
Nuria Kotecki ◽  
Fred Dijcks ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Tumor Tissue ◽  
Staining Method ◽  
Soft Tissue Sarcomas ◽  
Tissue Microarrays ◽  
Histological Subtypes ◽  
Scoring Method ◽  
Drug Conjugates ◽  
High Prevalence ◽  
Quantitative Scoring

The expression of 5T4/trophoblast glycoprotein was evaluated in several histological subtypes of soft tissue sarcoma (STS) to determine whether the prevalence and level of expression of this membrane-associated glycoprotein is sufficient for use in targeted therapies. Tumor tissue microarrays containing cores from different histological subtypes of STS were stained using a standardized immunohistochemical staining method to detect 5T4; the level of staining was assessed using a semi-quantitative scoring method. No 5T4 staining was seen in the angiosarcomas and liposarcomas investigated in this study. 5T4 staining in the other STS subtypes was seen in more than 50% of cases, warranting further investigation into whether this antigen could evoke an anti-tumor immune response or can be used as target for the delivery of more potent toxins through antibody drug conjugates.

Predictive value of MRP-1 in localized high-risk soft tissue sarcomas: a translational research associated to ISG-STS 1001 randomized phase III trial.

2021 ◽  
pp. molcanther.0315.2021
Author(s):  
Javier Martín-Broto ◽  
Maria Lopez-Alvarez ◽  
David S Moura ◽  
Rafael Ramos ◽  
Paola Collini ◽  
...  
Keyword(s):  
High Risk ◽  
Soft Tissue ◽  
Translational Research ◽  
Predictive Value ◽  
Soft Tissue Sarcomas ◽  
Phase Iii ◽  
Phase Iii Trial

scholarly journals The adhesion molecule CD44v6 is associated with a high risk for local recurrence in adult soft tissue sarcomas

2001 ◽  
Vol 84 (2) ◽  
pp. 244-252 ◽  
Author(s):  
S Maula ◽  
R L Huuhtanen ◽  
C P Blomqvist ◽  
T A Wiklund ◽  
P Laurila ◽  
...  
Keyword(s):  
High Risk ◽  
Soft Tissue ◽  
Local Recurrence ◽  
Adhesion Molecule ◽  
Soft Tissue Sarcomas

FSTL5 Is a Marker of Poor Prognosis in Non-WNT/Non-SHH Medulloblastoma

2011 ◽  
Vol 29 (29) ◽  
pp. 3852-3861 ◽  
Author(s):  
Marc Remke ◽  
Thomas Hielscher ◽  
Andrey Korshunov ◽  
Paul A. Northcott ◽  
Sebastian Bender ◽  
...  
Keyword(s):  
High Risk ◽  
Expression Patterns ◽  
Tissue Microarrays ◽  
Genetic Alterations ◽  
Good Prognosis ◽  
Marker Genes ◽  
Molecular Subgroup ◽  
Dismal Prognosis ◽  
Large Patient ◽  
Group D

Purpose Integrated genomics approaches have revealed at least four distinct biologic variants of medulloblastoma: WNT (wingless), SHH (sonic hedgehog), group C, and group D. Because of the remarkable clinical heterogeneity of group D tumors and the dismal prognosis of group C patients, it is vital to identify molecular biomarkers that will allow early and effective treatment stratification in these non-WNT/non-SHH tumors. Patients and Methods We combined transcriptome and DNA copy-number analyses for 64 primary medulloblastomas. Bioinformatic tools were used to discover marker genes of molecular variants. Differentially expressed transcripts were evaluated for prognostic value in the screening cohort. The prognostic power of follistatin-like 5 (FSTL5) immunopositivity was tested for 235 nonoverlapping medulloblastoma samples on two independent tissue microarrays. Results Comprehensive analyses of transcriptomic and genetic alterations delineate four distinct variants of medulloblastoma. Stable subgroup separation was achieved by using the 300 transcripts that varied the most. Distinct expression patterns of FSTL5 in each molecular subgroup were confirmed by quantitative real-time polymerase chain reaction. Immunopositivity of FSTL5 identified a large cohort of patients (84 of 235 patients; 36%) at high risk for relapse and death. Importantly, more than 50% of non-WNT/non-SHH tumors displayed FSTL5 negativity, delineating a large patient cohort with a good prognosis who would otherwise be considered intermediate or high-risk on the basis of current molecular subgrouping. Conclusion FSTL5 expression denoted a dismal prognosis both within and across medulloblastoma subgroups. The addition of FSTL5 immunohistochemistry to existing molecular stratification schemes constitutes a reliable and cost-effective tool for prognostication in future clinical trials of medulloblastoma.

Adult-Type Soft Tissue Sarcomas in Pediatric-Age Patients: Experience at the Istituto Nazionale Tumori in Milan

2005 ◽  
Vol 23 (18) ◽  
pp. 4021-4030 ◽  
Author(s):  
Andrea Ferrari ◽  
Michela Casanova ◽  
Paola Collini ◽  
Cristina Meazza ◽  
Roberto Luksch ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Complete Resection ◽  
High Grade ◽  
Adult Type ◽  
Free Survival ◽  
Homogeneous Subgroup ◽  
Response To Chemotherapy ◽  
Patients Experience ◽  
Rate Of Response

Purpose Nonrhabdomyosarcoma soft tissue sarcomas are a heterogeneous group of tumors for which optimal treatment remains controversial. We report on a large group of 182 patients younger than 18 years old treated at a single institution over a 25-year period. Patients and Methods In this relatively homogeneous subgroup of adult-type histotypes, surgery was the mainstay of treatment; radiotherapy was administered to 73 patients, and chemotherapy was administered to 114 patients (70 received chemotherapy as adjuvant therapy). Results Overall survival at 5 years was 89% in patients who underwent complete resection at diagnosis, 79% in patients who had marginal resection, 52% in initially unresected patients, and 17% in patients with metastases at onset. Outcome was unsatisfactory in patients with large and high-grade tumors, even after gross resection; adjuvant chemotherapy seemed to improve the results in this group. Initially unresected patients who responded well to chemotherapy and subsequently underwent complete resection had an event-free survival rate of approximately 70%. The rate of response to chemotherapy was 58%. Conclusion The identification of prognostic variables should enable risk-adapted therapies to be planned. Patients with initially unresectable disease and patients with resected large and high-grade tumors are at high risk of metastases and treatment failure. Although the limits of this retrospective analysis are self-evident, our data would suggest that intensive chemotherapy (with an ifosfamide-doxorubicin regimen) might have a more significant role in these patients than what is generally assumed.

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