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Estrogen receptor β in NSCLC: prevalence, proliferative influence, prognostic impact and smoking
Örebro University, School of Health and Medical Sciences.
Dept of Laboratory Medicine Örebro University Hospital, SE70185 Örebro, Sweden.
Dept of Thoracic Surgery Örebro University Hospital, SE70185 Örebro, Sweden.
School of Health and Medical Sciences, Örebro University, SE70182 Örebro, Sweden, and Dept of Laboratory Medicine, Örebro University Hospital, SE70185 Örebro, Sweden.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

In non-small cell lung carcinoma (NSCLC) there are gender differences. The female gender is associated with more adenocarcinomas (ADCA), among both smokers and non-smokers compared to men. Women with NSCLC have a better prognosis compared to men, regardless of other factors. A possible role for estrogen receptor (ER) signalling has been proposed and experimental as well as epidemiological data supports this view. In a material of NSCLC (n=262), ERβ and cyclins A and A2 were studied by immunohistochemistry on formalin-fixed paraffin embedded tissue. In 137 of those cases, frozen material was available, on which expression analysis of ESR2 (ERβ) and cyclin A1 were performed. Data was correlated to histology, gender, smoking habits, stage and clinical outcome.

ERβ was expressed in 86% of the cases. ERβ was most frequently expressed in Stage I ADCAs, especially in male subjects. A correlation between ERβ expression and cyclins was observed in ADCA, also with a male predominance. ERβ transcripts had a positive prognostic impact in ADCA. ERβ transcripts were also increased in NSCLC among smokers compared to non-smokers.

In conclusion, we report data supporting a role for ERβ in lung ADCAs where ERβ could be a biomarker for future targeted therapies.

Keywords [en]
NSCLC, ERβ, immunohistochemistry, gene expression, gender, prognosis, smoking habits
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-20596OAI: oai:DiVA.org:oru-20596DiVA, id: diva2:467323
Available from: 2011-12-19 Created: 2011-12-19 Last updated: 2017-10-17Bibliographically 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. p. 86
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 61
Keywords
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

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Karlsson, Christina

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