Expression von Differenzierungsmarkern in kombinierten kleinzelligen Bronchialkarzinomen

Most small cell lung cancer (SCLC) patients relapse within 12 months of starting combination chemotherapy plus radio-therapy, due to the development of acquired chemo and radio-resistance. This phenomenon relates to the induction of tumour differentiation, resulting in apoptosis-resistant, morphologically variant (v-SCLC) cells, which lack the neuroendocrine expression of classic (c-) SCLC cells. This dissertation was part of a study in which spontaneously adherent SCLC sub lines were shown by differential gene expression analysis to provide an in vitro model of variant differentiation in SCLC, with downregulation of neuroendocrine markers and upregulation of epithelial differentiation markers cyclin D1, endothelin, cell adhesion molecules CD 44 and integrin subunits α2, β3, β4. We could show the reversibility of this process of transdifferentiation with an increase in the expression of L-Dopa-Decarboxylase and a decrease of the expression of CD 44 and integrin subunits. In a last step we tried to proof the hypothesis of our study model in combined SCLC with immunhistochemical staining for CD 44 in paraffin conserved lung cancers. We could show a nearly similar distribution in the subgroups. We conclude that our findings help to explain tumour differentiation in SLCL and NSCLC in vitro. Our results can help to create a new model of the development of acquired chemo and radio-resistance in SLCL. The conversion of the in-vitro-results for the in vivo pathogenesis of SCLC seems possible based on the immunhistochemical datas for CD 44. Further studies of others cell cultures and for other appropriate differentiation markers for exploration of SCLC is necessary for better strategies in the therapy of lung cancer.