oru.sePublikationer
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Prognostic impact of the expression of Wnt-signaling proteins in cervical carcinoma FIGO stage I-IV treated with radiotherapy or chemoradiotherapy
Orebro University Hospital. Department of Oncology.
Department of Oncology, Örebro University Hospital, Örebro, Sweden.
Orebro University Hospital. Department of Oncology.
2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 39, 63042-63053 p.Article in journal (Refereed) Published
Abstract [en]

Wnt signaling proteins were assessed in patients with primary cervical carcinomas who received chemoradiation. The associations between three Wnt signaling proteins and prognosis were assessed. Specimens from 122 patients with cervical carcinomas (FIGO stage I-IV) were immunohistochemically (IHC) analyzed for β-catenin, APC and axin protein expression. Associations between these Wnt-protein expressions, clinicopathological factors, and clinical outcome data were examined.Positive IHC staining for the β-catenin protein (cell-membranes, cytoplasm and nuclei) was recorded in 88%, 58% and 5%, respectively. There was a strong association between β-catenin staining of the cell-membranes and prediction of recurrences and prognosis (p = 0. 002). Tumors with > 5% of nuclear β-catenin staining were associated with inferior cancer-specific survival (p = 0.048) compared with no staining. The overall recurrence rate was significantly higher in the group with increased nuclear staining (67%) compared with the group with no staining (33%). Nuclear APC staining of high intensity was associated with a significantly worse cancer-specific survival and increased overall recurrence rate compared to tumors with weak staining. Distant recurrences were recorded in 29% of cases with intense staining and in 14% of cases with low staining.The Wnt signaling pathway seems to be of importance in the process of cervical oncogenesis. A predictive and prognostic value was found for β-catenin, where strong cell-membrane staining was favorable, and > 5% positive nuclear staining was associated with poorer cancer-specific survival and overall recurrence rate. Nuclear APC staining intensity was also associated with a less favorable prognosis.

Place, publisher, year, edition, pages
2016. Vol. 7, no 39, 63042-63053 p.
Keyword [en]
APC, Wnt signaling pathway, cervical carcinoma, β-catenin
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-56900DOI: 10.18632/oncotarget.11642PubMedID: 27577083Scopus ID: 2-s2.0-84994045434OAI: oai:DiVA.org:oru-56900DiVA: diva2:1085570
Available from: 2017-03-29 Created: 2017-03-29 Last updated: 2017-03-29Bibliographically approved
In thesis
1. Predictive and prognostic factors in cervical carcinomas treated with (chemo-) radiotherapy
Open this publication in new window or tab >>Predictive and prognostic factors in cervical carcinomas treated with (chemo-) radiotherapy
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A series of 131 women with cervical carcinoma FIGO stage I-IV were treated with external radiotherapy and intracavitary brachytherapy. In 47 patients (36%) concomitant chemotherapy was given. One hundred and twenty-one tumors (92%) achieved complete remission. Addition of chemotherapy increased primary cure rate to 98%. Tumor stage, tumor size, and histology were significant predictive factors for primary cure. Treatment related factors were: brachytherapy dose and interruption of irradiation.

Thirty-nine recurrences (30%) were recorded. Tumor stage, histology, and concomitant chemotherapy were significant predictive factors.

The 5-year cancer-specific survival rate of the complete series was 65%. Tumor size was a strong prognostic factor in multivariate analysis.

Serum samples from 44 patients were analyzed. Ten candidate biomarker proteins with regard to tumor recurrences were identified.

Five Hedgehog proteins were analyzed with immunohistochemistry. Residual tumor, local and distant recurrences and survival rate were associated with PTCH, SMO and GLI2. In the Wnt-β-catenin study intense staining of the membranes and nuclear staining > 5% were of significant predictive and prognostic value. Intense nuclear APC staining was associated with recurrences and cancer-specific survival rate.

Conclusion: Histology, tumor size and brachytherapy dose were important clinical predictive and prognostic factors. Multiprotein analysis identified ten biomarker proteins associated with tumor recurrences. Three proteins (PTCH, SMO, and GLI2) in the Hedgehog pathway were of predictive and prognostic value. In the Wnt-β-catenin pathway intensity of β-catenin membrane staining and accumulation in the nuclei as well as nuclear APC-expression were of predictive and prognostic value.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2017. 61 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 159
Keyword
cervical carcinoma, radio-chemotherapy, biomarkers, predictive factors, prognostic factors, multiprotein analysis, Hedgehog pathway, Wnt/β-catenin pathway
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:oru:diva-56127 (URN)978-91-7529-185-7 (ISBN)
Public defence
2017-04-21, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2017-03-06 Created: 2017-03-06 Last updated: 2017-04-19Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Bohr Mordhorst, LouiseSorbe, Bengt
By organisation
Orebro University Hospital
In the same journal
OncoTarget
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 15 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf