The neurotensin (NT) receptor, NTS3, originally identified as the intracellular sorting protein sortilin, is a member of a recently discovered family of receptors characterized by a single transmembrane domain. The present study provides the first comprehensive description of the distribution of NTS3/sortilin mRNA and protein in adult rat brain using in situ hybridization and immunocytochemistry. Both NTS3/sortilin mRNA and immunoreactivity displayed a widespread distribution throughout the brain. High levels of NTS3/sortilin expression and immunoreactivity were found in neuronal cell bodies and dendrites of allocortical areas such as the piriform cortex and hippocampus. Regions expressing both high levels of NTS3/sortilin mRNA and protein also included several neocortical areas, the islands of Calleja, medial and lateral septal nuclei, amygdaloid nuclei, thalamic nuclei, the supraoptic nucleus, the substantia nigra, and the Purkinje cell layer of the cerebellar cortex. In the brainstem, all cranial nerve motor nuclei were strongly labeled. NTS3/sortilin mRNA and immunoreactivity were also detected over oligodendrocytes in major fiber tracts. Subcellularly, NTS3/sortilin was predominantly concentrated over intracytoplasmic membrane-bound organelles. Many of the areas exhibiting high levels of NTS3/sortilin (e.g., olfactory cortex, medial septum, and periaqueductal gray) have been documented to contain high concentrations of NT nerve cell bodies and axons, supporting the concept that NTS3/sortilin may play a role in NT sorting and/or signaling. Other areas (e.g., hippocampal CA fields, cerebellar cortex, and cranial nerve motor nuclei), however, are NT-negative, suggesting that NTS3/sortilin also exerts functions unrelated to NT signaling.

The aim of this study was to evaluate the immunohistochemical expression of phospho-Akt and its possible association with clinicopathological features in uveal melanoma. Thirty-four enucleated eyes from 34 patients with choroidal melanoma were included in the study. Patients were divided into two groups based on the treatment received: (1) primary enucleation (n=18); (2) radiotherapy, either external beam or brachytherapy, and enucleation (n=16). Clinicopathological data were obtained. The minimum follow-up time was 72 months. Immunohistochemistry for phospho-Akt was performed using an anti-phospho-Akt (Ser 473) rabbit antibody. The association of phospho-Akt with clinicopathological parameters was investigated in each patient group separately. Phospho-Akt immunostaining was cytoplasmic in both groups. In the primary enucleation group, 10 tumours were phospho-Akt positive (55.5%). Patients with phospho-Akt-positive tumours were older (average 70.8 years versus 59 years, P=0.01) and phospho-Akt immunoreactivity was significantly associated with a higher risk of metastatic disease (Kaplan-Meier analysis, P=0.02). In the radiotherapy and enucleation group, nine tumours were phospho-Akt positive (56.2%). The absence of phospho-Akt expression was correlated with male gender (P=0.02). The following conclusions can be drawn from this study: (1) phospho-Akt immunoexpression was detected in 55.5% of uveal melanomas treated with primary enucleation and in 56.2% of uveal melanomas treated with radiotherapy and enucleation; (2) the association of phospho-Akt immunoexpression with clinicopathological features, including prognosis, merits further study.

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