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
Tissue microarray validation: a methodologic study with special reference to lung cancer
Örebro University, School of Health and Medical Sciences.
Örebro University, School of Health and Medical Sciences.
Örebro University, School of Health and Medical Sciences.ORCID iD: 0000-0001-6881-237X
2009 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, no 7, 2014-2021 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Although tissue microarray (TMA) studies of histopathologic material have been frequently reported in studies of malignant diseases, the question of sample size (i.e., the diameter and the number of tissue cylinders investigated) has been rarely discussed. This study addresses the methodologic question of sample size in a variety of tumor types.

MATERIAL AND METHODS: Material from 29 cases of lung carcinoma (small cell, squamous cell, and adenocarcinomas) was examined immunohistochemically for Ki-67 and p53 expression in virtually constructed cylinders of different diameters. The influence of tissue sample size (i.e., different numbers of virtual cylinders) was also investigated. Results from Ki-67 evaluation were analyzed as a continuous variable, whereas p53 expression was scored. p53 evaluations based on scoring in cylinders versus scoring of whole sections were also compared. Furthermore, 10 cases of endometrial and breast carcinomas were evaluated for estrogen receptor, Ki-67, and HER2 by scoring up to five cylinders.

RESULTS AND CONCLUSIONS: Tissue cylinders of 0.6 and 1.0 mm diameters were compared and found equally informative about Ki-67 expression (intraclass correlation, 0.96). A statistical approach considering intraindividual and interindividual variation data is presented, indicating that in this specific setting three cylinders per case is an adequate sample size for TMA studies. Further sampling yields only a small gain in accuracy as determined by Ki-67 quantification and p53 scoring (kappa-coefficient, 0.9). For endometrial and breast tissues, TMA scoring of three cylinders yielded excellent agreement (kappa, >0.75) compared with whole-section scoring.

Place, publisher, year, edition, pages
American Association for Cancer Research , 2009. Vol. 18, no 7, 2014-2021 p.
National Category
Medical and Health Sciences Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-12067DOI: 10.1158/1055-9965.EPI-08-0743ISI: 000268059700010PubMedID: 19531681Scopus ID: 2-s2.0-67650462275OAI: oai:DiVA.org:oru-12067DiVA: diva2:355143
Available from: 2010-10-05 Created: 2010-10-05 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Biomarkers in non-small cell lung carcinoma: methodological aspects and influence of gender, histology and smoking habits on estrogen receptor and epidermal growth factor family receptor signalling
Open this publication in new window or tab >>Biomarkers in non-small cell lung carcinoma: methodological aspects and influence of gender, histology and smoking habits on estrogen receptor and epidermal growth factor family receptor signalling
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Non-small cell lung carcinoma is a leading cause of cancer mortality worldwide. There are gender and smoking associated differences both in tumour types and clinical outcome. Squamous cell carcinomas (SCC) are more frequent among smoking men while females develop adenocarcinomas (ADCA). NSCLC among never smokers are mainly ADCA, and occurs mostly in females. The present thesis elucidates the role of estrogen receptor (ER) and epidermal growth factor receptor family (EGFR/HER2-4) in NSCLC in the perspective of gender and histology as well as the influence of smoking on those biomarkers.

A recently developed technique, tissue micro array (TMA), was employed.The question of how much of a tumour tissue that needed to be included in a TMA for biomarker analysis was analyzed by a statistical approach. Data indicates a sample size of three cylinders of tumour tissue with a diameter of 0.6 mm each as being appropriate and cost-effective. In order to optimally use the up to thousands of different tumour samples within a TMA, it would be optimal to serially cut and store slides before performing in situ detection of proteins and nucleic acids. Applying up to date methodology, and by evaluation with image analysis, data are presented that shows that such handling of TMA slides would be possible without any loss of biomarker information.

ERα is more frequently observed in ADCA and in females and a local estradiol synthesis is supported by the presence of aromatase. ERβ is identified as a positive prognostic marker in ADCA. Smoking is associated to increased levels of ERβ mRNA. EGFR over expression is associated with a ligand. Independent phosporylation of ERα. HER-4 intracellular domain may also act as a co-activator to ERα in ADCA, especially among neversmokers. The question of ER and EGFR family signalling crosstalk as a potential target for combined targeted therapy is raised.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2011. 86 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 61
Keyword
Non-small cell lung carcinoma, estrogen receptor, epidermal growth factor receptor, HER-4, tissue microarray, immunohistochemistry, smoking habits, in situ hybridisation
National Category
Medical and Health Sciences Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-19725 (URN)978-91-7668-827-4 (ISBN)
Public defence
2011-11-25, Hörsal P1, Örebro universitet, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2011-10-06 Created: 2011-10-06 Last updated: 2017-10-17Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Authority records BETA

Karlsson, ChristinaBodin, LennartPiehl-Aulin, KarinKarlsson, Mats G.

Search in DiVA

By author/editor
Karlsson, ChristinaBodin, LennartPiehl-Aulin, KarinKarlsson, Mats G.
By organisation
School of Health and Medical Sciences
In the same journal
Cancer Epidemiology, Biomarkers and Prevention
Medical and Health SciencesCancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 323 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