Expression of doublecortin in tumours of the central and peripheral nervous system and in human non-neuronal tissues

Abstract

Doublecortin is a microtubule-associated phosphoprotein involved in neuronal migration and differentiation expressed in migrating neuroblasts in the central nervous system. We systematically analysed doublecortin expression in 179 tumours of the central and 65 tumours of peripheral nervous system as well as in 74 different non-neuronal tissues to evaluate the specificity of doublecortin as a marker for neuronal differentiation in glioneuronal tumours. Glioneuronal tumours and oligodendrogliomas grade II and III uniformly showed a high intensity and frequency of doublecortin staining, whereas intermediate doublecortin expression was observed in astrocytic tumours of grade II-IV. In pilocytic astrocytomas and ependymomas only scattered doublecortin positive cells were detected. In the peripheral nervous system, doublecortin expression was found in neurofibroma but was absent in schwannoma. Double staining of tumour tissue revealed co-expression of doublecortin and neurofilament in cells of gangliocytomas and gangliogliomas and co-expression of doublecortin with S100 protein or GFAP in glial tumours, respectively. In a tissue array comprised of 74 different normal non-neuronal human tissues, doublecortin expression was demonstrated in epithelia of the kidney, liver, salivary glands and duodenum among others. Interestingly, doublecortin expression could not be shown in brain metastases of tumours originating from these tissues. Immunohistochemical data was further corroborated by Western blot analysis and reverse transcription polymerase chain reaction. In conclusion, doublecortin can be regarded as specific neuronal marker only in normal developing brain, but lacks specificity in glioneuronal and glial tumours and other non-neuronal human tissues where it is expressed in a wide variety of tumours and tissues.