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Soft Tissue Sarcoma Patterns multiplicity, heterogeneity and growth characteristics

Fernebro, Josefin LU (2007) In 2007:88
Abstract
Soft tissue sarcomas (STS) represent a group of rare and heterogenous tumors that optimally should be diagnosed and treated within multidisciplinary teams. This thesis has studied various aspects ? pathological, genetical, and clinical ? of STS.



In study I, we demonstrated that 20% of the patients in a population-based series of 818 STS developed second primary malignancies. An increased risk of developing a second malignancy was identified (SMR 1.3; 95% CI=1.0-1.5), with a particularly high risk of developing a second STS (SMR 17.6; 95% CI=8.1-33.5).



Study II included 13 patients who had developed at least two primary STS and we applied array-based comparative genomic hybridization to study the... (More)
Soft tissue sarcomas (STS) represent a group of rare and heterogenous tumors that optimally should be diagnosed and treated within multidisciplinary teams. This thesis has studied various aspects ? pathological, genetical, and clinical ? of STS.



In study I, we demonstrated that 20% of the patients in a population-based series of 818 STS developed second primary malignancies. An increased risk of developing a second malignancy was identified (SMR 1.3; 95% CI=1.0-1.5), with a particularly high risk of developing a second STS (SMR 17.6; 95% CI=8.1-33.5).



Study II included 13 patients who had developed at least two primary STS and we applied array-based comparative genomic hybridization to study the genetic profiles of these tumors. Cluster anaysis and comparison between the genetic profiles suggested that 8 cases represented second primary STS, whereas 5 cases likely represented soft tissue metastases.



In study III cDNA microarray was applied to 26 synovial sarcomas and identified differentially expressed genes in relation to gene fusion type. Among the discriminators were several genes that have previously been found to be up-regulated in SS, including AXL, ZIC2, SPAG7, AGRN, FOXC1, NCAM1.



In study IV we assessed the impact of targeting peripheral versus central tumor areas using tissue microarray-based staining for Ki-67 in leiomyosarcomas and demonstrated that the Ki-67 expression was higher in the tumor periphery in 18/25 tumors. These observations suggest that Ki-67 evaluation for prognostic purposes should be standardized regarding the part of the tumor investigated.



In study V, peripheral tumor growth pattern was evaluated on preoperative MRI with correlations to microscopical growth pattern and prognosis. All tumors with diffuse infiltration on MRI also showed microscopical infiltration, whereas MRI failed to identify infiltration in one-third of the microscopically infiltrative tumors. Diffusely infiltrative growth on MRI correlated with prognosis with a 2.5 times increased risk of metastases (p=0.01) and a 3.7 times higher risk of local recurrence (p=0.02).



In summary, we have demonstrated that patients with STS are at increased risk of developing second primary tumors, including STS, with genetic profiles supporting independent tumor origin. We have also demonstrated that the underlying gene fusion type in synovial sarcoma influence the gene expression profile. Finally, the tumor periphery seems to provide the best information; our studies suggest that evaluation of Ki-67 staining should be standardized, perhaps to the periphery, and that MRI-based classification of the peripheral tumor growth pattern may provide prognostic information (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Prof. Bruland, Oyvind, Oslo
organization
publishing date
type
Thesis
publication status
published
subject
keywords
cancerology, Cytologi, oncology, Soft tissue sarcoma, tumor periphery, Medicine (human and vertebrates), Medicin (människa och djur), Cytology, multiple primary tumors, onkologi, cancer
in
2007:88
pages
47 pages
publisher
Department of Clinical Sciences, Lund University
defense location
Föreläsningssalen, Barngatan 2, Universitetssjukhuset, Lund.
defense date
2007-05-24 09:00:00
ISSN
1652-8220
ISBN
978-91-85559-66-4
language
English
LU publication?
yes
additional info
Josefin Fernebro, Anna Bladström, Anders Rydholm, Pelle Gustafson, Håkan Olsson, Jacob Engellau and Mef Nilbert. 2006. Increased risk of malignancies in a population-based study of 818 soft-tissue sarcoma patients. British Journal of Cancer, vol 95 pp 1-5. Lund University
Josefin Fernebro, Ana Carneiro, Anders Rydholm, Anna Karlsson, Åke Borg and Mef Nilbert. . Multiple Soft Tissue Sarcomas; genetic profiling differentiates metastases and new primary tumors pp 9. (manuscript)
Josefin Fernebro, Princy Francis, Patrik Eden, Åke Borg, Ioannis Panagopoulos, Fredrik Mertens, Johan Vallon-Christersson, Måns Åkerman, Anders Rydholm, Henrik Bauer, Nils Mandahl and Mef Nilbert. 2006. Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma. International Journal of Cancer, vol 118 pp 1165-1172.
Josefin Fernebro, Jacob Engellau, Annette Persson, Anders Rydholm and Mef Nilbert. 2007. Standardizing Evaluation of Sarcoma Proliferation; higher Ki-67 expression in the tumor periphery than the center. APMIS, pp 6. (inpress)
Josefin Fernebro, Marie Wiklund, Kjell Jonsson, Bendahl Pär-Ola, Anders Rydholm, Mef Nilbert and Jacob Engellau. 2006. Focus on the tumour periphery in the MRI evaluation of soft tissue sarcoma: infiltrative growth signifies poor prognosis. Sarcoma, vol 2006 pp 1-5.
id
4fa7a4bd-b5f8-450d-90fe-5ed09fe28aff (old id 548635)
date added to LUP
2016-04-01 15:41:55
date last changed
2019-05-21 08:47:29
@phdthesis{4fa7a4bd-b5f8-450d-90fe-5ed09fe28aff,
  abstract     = {{Soft tissue sarcomas (STS) represent a group of rare and heterogenous tumors that optimally should be diagnosed and treated within multidisciplinary teams. This thesis has studied various aspects ? pathological, genetical, and clinical ? of STS.<br/><br>
<br/><br>
In study I, we demonstrated that 20% of the patients in a population-based series of 818 STS developed second primary malignancies. An increased risk of developing a second malignancy was identified (SMR 1.3; 95% CI=1.0-1.5), with a particularly high risk of developing a second STS (SMR 17.6; 95% CI=8.1-33.5).<br/><br>
<br/><br>
Study II included 13 patients who had developed at least two primary STS and we applied array-based comparative genomic hybridization to study the genetic profiles of these tumors. Cluster anaysis and comparison between the genetic profiles suggested that 8 cases represented second primary STS, whereas 5 cases likely represented soft tissue metastases.<br/><br>
<br/><br>
In study III cDNA microarray was applied to 26 synovial sarcomas and identified differentially expressed genes in relation to gene fusion type. Among the discriminators were several genes that have previously been found to be up-regulated in SS, including AXL, ZIC2, SPAG7, AGRN, FOXC1, NCAM1.<br/><br>
<br/><br>
In study IV we assessed the impact of targeting peripheral versus central tumor areas using tissue microarray-based staining for Ki-67 in leiomyosarcomas and demonstrated that the Ki-67 expression was higher in the tumor periphery in 18/25 tumors. These observations suggest that Ki-67 evaluation for prognostic purposes should be standardized regarding the part of the tumor investigated.<br/><br>
<br/><br>
In study V, peripheral tumor growth pattern was evaluated on preoperative MRI with correlations to microscopical growth pattern and prognosis. All tumors with diffuse infiltration on MRI also showed microscopical infiltration, whereas MRI failed to identify infiltration in one-third of the microscopically infiltrative tumors. Diffusely infiltrative growth on MRI correlated with prognosis with a 2.5 times increased risk of metastases (p=0.01) and a 3.7 times higher risk of local recurrence (p=0.02).<br/><br>
<br/><br>
In summary, we have demonstrated that patients with STS are at increased risk of developing second primary tumors, including STS, with genetic profiles supporting independent tumor origin. We have also demonstrated that the underlying gene fusion type in synovial sarcoma influence the gene expression profile. Finally, the tumor periphery seems to provide the best information; our studies suggest that evaluation of Ki-67 staining should be standardized, perhaps to the periphery, and that MRI-based classification of the peripheral tumor growth pattern may provide prognostic information}},
  author       = {{Fernebro, Josefin}},
  isbn         = {{978-91-85559-66-4}},
  issn         = {{1652-8220}},
  keywords     = {{cancerology; Cytologi; oncology; Soft tissue sarcoma; tumor periphery; Medicine (human and vertebrates); Medicin (människa och djur); Cytology; multiple primary tumors; onkologi; cancer}},
  language     = {{eng}},
  publisher    = {{Department of Clinical Sciences, Lund University}},
  school       = {{Lund University}},
  series       = {{2007:88}},
  title        = {{Soft Tissue Sarcoma Patterns multiplicity, heterogeneity and growth characteristics}},
  url          = {{https://lup.lub.lu.se/search/files/4451716/548636.pdf}},
  year         = {{2007}},
}