Expressionsverhalten von ABC-A3 in Nicht-kleinzelligen Bronchialkarzinomen - ein neoadjuvantes Therapiekonzept
von Dorothee Höner geb. Kaufmann
Datum der mündl. Prüfung:2022-06-09
Betreuer:Prof. Dr. Bernhard C. Danner
Gutachter:Prof. Dr. Bernhard C. Danner
Gutachter:Dr. Achim PD. Rittmeyer
EnglischATP-binding cassette transporter protein ABCA3 is known to be responsible for drug resistance. This respectively study examined the expression of ABCA3 as a possible predictive marker for a response to chemotherapy. The hypothesis is: a high expression of ABCA3 in patients with diagnosed NSCLC correlates with a low response to chemotherapy. Methods: The study collectives includes 31 patients with diagnosed NSCLC. All patients received four cycles of chemotherapy with docetaxel and cisplatin, this was followed by tumor resection and PORT. Histological tumor samples of these patients (from histological tumor protection and postchemotherapeutic tumor resection) were immunohistochemically stained and examined for the expression of ABCA3. The intensity of staining were evaluated (qualitative) by using light microscopy. A modification of the h-score, called positive index (PI), showed the qualitative and quantitative evaluation. Correlations of ABCA3 expression and clinical parameters were calculated using the spearman correlation. Results: By using the Kaplan Meier Survival, patients with low or high ABCA3 expression, represented in the results of maximum intensity and PI, showed no difference in survival time. The comparison between the expression of ABCA3 before and after chemotherapy showed no frequencies (McNemar test). A high expression of ABCA3 was correlated with female sex, non-smoker and older patients (>61 years). Conclusion: For this study collectice the expression of ABCA3 does not affect the survival time of the patients with NSCLC, so the protein does not appear to be suitable as a predictive marker for responding to chemotherapy. This study is limited by the small number of patients so the role of ABCA3 in NSCLC has not been conclusively clarified. In a previous study female sex, non-smoker and older patients and were also correlated with a high expression of ABCA3, so it is conceivable that these patients have a mutation in the protein-coding genome. This requires further studies.
Keywords: NSCLC; Non-Small Cell Lung Cancer; ABCA3; Neoadjuvant therapy