Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Kuchler, C.
Analysis of immunohistochemical expression of DLL3, TP53 and RB1 in the patients with small cell and large cell neuroendocrine carcinoma of the lung
Humanmedizin; [ Diplomarbeit ] Medical University of Graz; 2019. pp. 57
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Absenger Gudrun
- Brcic Luka
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- Abstract:
- Introduction: Lung cancer is one of the most prevalent malignancies in the world. Nearly one out of five cancer related deaths is caused by lung cancer. Patients with small cell lung cancer are diagnosed at an advanced stage and have a very poor prognosis due to early metastasis and rapid growth. Unfortunately, until today there is no significant improvement in therapy. Recently, a clinical phase 1 study of an antibody-drug conjugate against DLL3 (Rovalpituzumab tesirine) showed promising results. In order to identify patients with a higher probability of response to this therapy, DLL3 expression analysis is required. However, not all pathological laboratories will be able to use antibody applied in clinical study, due to the need of adequate technical equipment. Because of this, we aimed to compare concordance of expression of four different DLL3 antibodies in LCNEC and SCLC. Methods: Study cohort included 53 surgically removed samples of LCNEC (29) and SCLC (24). Tissue microarrays were constructed and used for immunohistochemical analysis. Four different antibodies targeting DLL3 were used. Slides were analysed under microsope. Percentage of positive tumour cells, and H score (percentage of positive tumour cells multiplied by intensity of the staining) were recorded. Standard antibodies for p53 and Rb1 were also used. Staining results for both were expressed as percentage of positive tumour cells. The same staining was repeated in validation cohort, consisting of 46 SCLC. Obtained results were correlated with survival data. Results: The expression of DLL3 was different with each antibody, regardless of the type of tumour and the used cut-off values. Furthermore, no correlation between the expression of DLL3 and a RB1 loss was observed in LCNEC. In SCLC we have found a positive correlation of DLL3 expression with a loss of RB1. Conclusion: We have shown that results obtained using different DLL3 antibodies are not concordant, and these antibodies are not interchangeable. Evaluation of DLL3 expression, is however, feasible, and it was present both in SCLC and in LCNEC, but without any prognostic significance.