Soft Tissue Sarcoma Patterns multiplicity, heterogeneity and growth characteristics

Josefin Fernebro

Research output: ThesisDoctoral Thesis (compilation)

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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
Original languageEnglish
Awarding Institution
  • Breastcancer-genetics
  • Nilbert, Mef, Supervisor
  • Rydholm, Anders, Supervisor
  • Engellau, Jacob, Supervisor
Award date2007 May 24
ISBN (Print)978-91-85559-66-4
Publication statusPublished - 2007

Bibliographical note

Defence details

Date: 2007-05-24
Time: 09:00
Place: Föreläsningssalen, Barngatan 2, Universitetssjukhuset, Lund.

External reviewer(s)

Name: Bruland, Oyvind
Title: Prof.
Affiliation: Oslo


<div class="article_info">Josefin Fernebro, Anna Bladström, Anders Rydholm, Pelle Gustafson, Håkan Olsson, Jacob Engellau and Mef Nilbert. <span class="article_issue_date">2006</span>. <span class="article_title">Increased risk of malignancies in a population-based study of 818 soft-tissue sarcoma patients.</span> <span class="journal_series_title">British Journal of Cancer</span>, <span class="journal_volume">vol 95</span> <span class="journal_pages">pp 1-5</span>. <span class="journal_distributor">Lund University</span></div>
<div class="article_info">Josefin Fernebro, Ana Carneiro, Anders Rydholm, Anna Karlsson, Åke Borg and Mef Nilbert. <span class="article_issue_date"></span>. <span class="article_title">Multiple Soft Tissue Sarcomas; genetic profiling differentiates metastases and new primary tumors</span> <span class="journal_pages">pp 9</span>. (manuscript)</div>
<div class="article_info">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. <span class="article_issue_date">2006</span>. <span class="article_title">Gene expression profiles relate to SS18/SSX fusion type in synovial sarcoma.</span> <span class="journal_series_title">International Journal of Cancer</span>, <span class="journal_volume">vol 118</span> <span class="journal_pages">pp 1165-1172</span>.</div>
<div class="article_info">Josefin Fernebro, Jacob Engellau, Annette Persson, Anders Rydholm and Mef Nilbert. <span class="article_issue_date">2007</span>. <span class="article_title">Standardizing Evaluation of Sarcoma Proliferation; higher Ki-67 expression in the tumor periphery than the center.</span> <span class="journal_series_title">APMIS</span>, <span class="journal_pages">pp 6</span>. (inpress)</div>
<div class="article_info">Josefin Fernebro, Marie Wiklund, Kjell Jonsson, Bendahl Pär-Ola, Anders Rydholm, Mef Nilbert and Jacob Engellau. <span class="article_issue_date">2006</span>. <span class="article_title">Focus on the tumour periphery in the MRI evaluation of soft tissue sarcoma: infiltrative growth signifies poor prognosis.</span> <span class="journal_series_title">Sarcoma</span>, <span class="journal_volume">vol 2006</span> <span class="journal_pages">pp 1-5</span>.</div>

Subject classification (UKÄ)

  • Cancer and Oncology


  • cancerology
  • Cytologi
  • oncology
  • Soft tissue sarcoma
  • tumor periphery
  • Medicine (human and vertebrates)
  • Medicin (människa och djur)
  • Cytology
  • multiple primary tumors
  • onkologi
  • cancer


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