Das Expressionsverhalten von ABCA3 und TTF-1 in nicht-kleinzelligen Bronchialkarzinomen

Expression patterns of ABCA3 and TTF-1 in Non-Small Cell Lung Cancer

by Johanna Friederike Arnemann
Doctoral thesis
Date of Examination:2016-09-26
Date of issue:2016-08-15
Advisor:PD Dr. Bernhard C. Danner
Referee:PD Dr. Bernhard C. Danner
Referee:Prof. Dr. Hans-Ulrich Schildhaus
Referee:Prof. Dr. Gerald Wulf
Persistent Address: http://dx.doi.org/10.53846/goediss-5806

 

 

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Abstract

English

Objectives: Clinical characteristics of non-small cell lung cancer (NSCLC) like poor outcome, high recurrence rates in low tumor stages and only temporary response to chemotherapy are caused by tumor cells with poorly understood resistance mechanisms. ATP-binding cassette transporter protein A3 (ABCA3) is known to be responsible for drug resistance. The present study examined whether the expression patterns of ABCA3 and thyroid transcription factor-1 (TTF-1) in NSCLC correlate with overall survival and other clinical characteristics. Methods: Paraffin-embedded lung tumor tissue samples from 89 patients were immunostained with antibodies against ABCA3 and TTF-1. The intensity of staining (quantitative and qualitative) was evaluated by using light microscopy. Correlations between the positive index (PI) of ABCA3 and TTF-1 and overall survival or other clinical characteristics were analyzed using log rank test and spearman correlation.  Results: The PI, a modification of the H-Score, was used to describe the quantitative and qualitative expression patterns of ABCA3 and TTF-1 respectively. The PI ranges between 0-300 with a threshold set at 100.  The group with a PI above the threshold for ABCA3 has a significantly poorer overall survival (p=0,044) as well as for TTF-1 (p=0,025). A high PI in ABCA3 is correlated with non-smoking. A high PI in TTF-1 is correlated with female sex and adenocarcinoma, a low PI with male sex and squamous cell carcinoma. No statistical correlation was observed between the expression of ABCA3 and TTF-1. Conclusion: The PI of ABCA3 and TTF-1 seems to be a suitable marker for NSCLC. The possible role of ABCA3 in drug resistance mechanisms in NSCLC patients may be able to explain the recent findings. Further prospective studies are warranted to validate the influence of drug resistance markers, resulting in possibly new therapeutic approaches.
Keywords: Non-Small Cell Lung Cancer; NSCLC; ABCA3; TTF-1
Schlagwörter: Nicht-kleinzellige Bronchialkarzinome; NSCLC; ABCA3; TTF-1
 
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