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Abstract
This work aimed at evaluate diagnosis and prognosis in soft tissue sarcoma (STS):
In study I, 32K bacterial artificial chromosome (BAC) arrays and gene expression
profiling were applied to 18 leiomyosarcomas and 31 undifferentiated pleomorphic
sarcomas (UPS), with the aim of identifying molecular subtype signatures. Both the
gains/losses profiles and the gene expression signatures revealed striking similarities
between the two tumour types. Leiomyosaromas and UPS were indistinguishable
using unsupervised hierarchical cluster analysis and significance analysis for
microarrays, which suggests a shared lineage.
In study II, whole-tumour sections from 239 STS were reviewed for size, vascular
invasion, necrosis, and peripheral growth pattern. All factors provided independent
prognostic information with hazard ratios (HRs) of 2.2-2.6 for development of
metastases in multivariate analysis. When combined into a prognostic model, referred
to as SING (Size, Invasion, Necrosis, Growth), high-risk tumours were identified
with a sensitivity of 74% and a specificity of 85%. SING compared favourably with
other currently used prognostic systems.
In study III, the prognostic value and clinical applicability of five proliferation
markers were assessed: Ki-67, Top2a, p21, p27Kip1 and S-phase fraction in a mixed
series of 196 STS of the extremities and the trunk wall, encompassing MFH/UPS,
leiomyosarcomas and liposarcomas. High S-phase fraction and high expression of Ki-
67 and Top2a significantly correlated to risk for metastasis with HRs of 1.9-4.4.
Classification and regression tree analysis showed that Ki-67, Top2a and S-phase
identified different prognostic subgroups. This explorative analysis suggests that
proliferation markers could have a role in STS prognostication, in particular when
few other factors can be evaluated, as in the preoperative setting.
In study IV, ezrin expression was evaluated by immunohistochemistry on tissue
microarrays from a mixed series of 256 STS. Positive ezrin expression predicted
development of metastasis (HR=1.8) and local recurrence (HR=1.8) and was strongly
correlated to necrosis and growth pattern. Ezrin represents therefore a potential
marker for identification of high-risk sarcoma patients.
In study I, 32K bacterial artificial chromosome (BAC) arrays and gene expression
profiling were applied to 18 leiomyosarcomas and 31 undifferentiated pleomorphic
sarcomas (UPS), with the aim of identifying molecular subtype signatures. Both the
gains/losses profiles and the gene expression signatures revealed striking similarities
between the two tumour types. Leiomyosaromas and UPS were indistinguishable
using unsupervised hierarchical cluster analysis and significance analysis for
microarrays, which suggests a shared lineage.
In study II, whole-tumour sections from 239 STS were reviewed for size, vascular
invasion, necrosis, and peripheral growth pattern. All factors provided independent
prognostic information with hazard ratios (HRs) of 2.2-2.6 for development of
metastases in multivariate analysis. When combined into a prognostic model, referred
to as SING (Size, Invasion, Necrosis, Growth), high-risk tumours were identified
with a sensitivity of 74% and a specificity of 85%. SING compared favourably with
other currently used prognostic systems.
In study III, the prognostic value and clinical applicability of five proliferation
markers were assessed: Ki-67, Top2a, p21, p27Kip1 and S-phase fraction in a mixed
series of 196 STS of the extremities and the trunk wall, encompassing MFH/UPS,
leiomyosarcomas and liposarcomas. High S-phase fraction and high expression of Ki-
67 and Top2a significantly correlated to risk for metastasis with HRs of 1.9-4.4.
Classification and regression tree analysis showed that Ki-67, Top2a and S-phase
identified different prognostic subgroups. This explorative analysis suggests that
proliferation markers could have a role in STS prognostication, in particular when
few other factors can be evaluated, as in the preoperative setting.
In study IV, ezrin expression was evaluated by immunohistochemistry on tissue
microarrays from a mixed series of 256 STS. Positive ezrin expression predicted
development of metastasis (HR=1.8) and local recurrence (HR=1.8) and was strongly
correlated to necrosis and growth pattern. Ezrin represents therefore a potential
marker for identification of high-risk sarcoma patients.
| Original language | English |
|---|---|
| Qualification | Doctor |
| Awarding Institution |
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| Supervisors/Advisors |
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| Award date | 2011 Jun 1 |
| Publisher | |
| ISBN (Print) | 978-91-86871-05-5 |
| Publication status | Published - 2011 |
Bibliographical note
Defence detailsDate: 2011-06-01
Time: 10:00
Place: Alwall Lecture Hall
External reviewer(s)
Name: Nielsen, Ole Steen
Title: MD, PhD
Affiliation: Department of Oncology, Aarhus University Hospital
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Subject classification (UKÄ)
- Cancer and Oncology
Free keywords
- MFH
- microarrays
- prognostic factors
- metastasis
- local recurrence
- proliferation
- Ki67
- Top2a
- p21
- p27
- S-phase fraction
- erzin.
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Dive into the research topics of 'Refined diagnosis and prognosis in soft tissue sarcoma - genetic profiles, biomarkers and prognostic models'. Together they form a unique fingerprint.Research output
- 2 Article
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A prognostic model for soft tissue sarcoma of the extremities and trunk wall based on size, vascular invasion, necrosis, and growth pattern.
Carneiro, A., Bendahl, P.-O., Engellau, J., Domanski, H., Fletcher, C. D., Rissler, P., Rydholm, A. & Nilbert, M., 2011, In: Cancer. Dec, p. 1279-1287Research output: Contribution to journal › Article › peer-review
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Indistinguishable genomic profiles and shared prognostic markers in undifferentiated pleomorphic sarcoma and leiomyosarcoma: different sides of a single coin?
Carneiro, A., Francis, P., Bendahl, P.-O., Fernebro, J., Åkerman, M., Fletcher, C., Rydholm, A., Borg, Å. & Nilbert, M., 2009, In: Laboratory Investigation. 89, p. 668-675Research output: Contribution to journal › Article › peer-review