Detection of Circulating Tumor Cells in Patients with Small Choroidal Melanocytic Lesions.

PURPOSE: To determine the presence of circulating tumor cells (CTCs) in patients with indeterminate small choroidal melanocytic lesions (SCMLs). DESIGN: Retrospective case series. PARTICIPANTS: Forty-seven patients with choroidal melanocytic lesions 2.5 mm or less in tumor thickness and ≤ 10 mm in largest basal diameter (LBD). METHODS: Blood samples were analyzed for CTCs and the presence of monosomy-3 (M3) in CTCs. Tissue biopsy was performed in the patients who were CTC-positive (pCTC). MAIN OUTCOME MEASURES: Presence and M3 status of the CTCs with regard to the clinical characteristics and results from tissue biopsy. RESULTS: Median thickness of all (n = 47) lesions was 1.1 mm (range: 0.2-2.5 mm), and LBD was 5.6 mm (range: 2.0-10.0 mm). Circulating tumor cells were found in 25 patients (n = 25). This group was classified as pCTC and compared with the CTC-negative (nCTC) group consisting of 22 patients (n = 22). Median tumor dimensions in the pCTC versus the nCTC group were 1.6 mm (range: 0.6-2.5 mm) versus 0.5 mm (range: 0.2-2.5 mm) for thickness and 6.6 mm (range: 4.1-10.0 mm) versus 4.0 mm (range: 2.0-8.0 mm) for LBD, respectively. Both LBD and thickness were positively associated (P < 0.001) with the presence of CTC. Compared with the nCTC group, a higher percentage of the pCTC group exhibited LBD > 5 mm (36% vs. 88%), subretinal fluid (9.1% vs. 56%), orange pigment (4.5% vs. 60%), sonographic hollowness (9.1% vs. 60%), and the presence of multiple risk factors (0% vs. 68% for ≥3 factors) with P < 0.001 for all parameters. No significant difference was detected in the clinical parameters of the patients who had disomy-3 (D3) (n = 7) versus M3 (n = 17) in their CTC. The tissue biopsy confirmed the uveal melanoma (UM) in 22 of the 25 pCTC patients (88%), whereas no conclusive diagnosis could be determined in the remaining 3 cases because of insufficient or invalid material. CONCLUSIONS: We report compelling evidence for the potential of liquid biopsy as an additional tool to screen SCMLs for malignancy. These findings pave the way toward the implementation of liquid biopsy to detect small UM and monitor melanocytic lesions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Systemic administration of neuregulin-1ß1 protects dopaminergic neurons in a mouse model of Parkinson's disease.

Neuregulin-1 (Nrg1) is genetically linked to schizophrenia, a disease caused by neurodevelopmental imbalance in dopaminergic function. The Nrg1 receptor ErbB4 is abundantly expressed on midbrain dopaminergic neurons. Nrg1 has been shown to penetrate blood-brain barrier, and peripherally administered Nrg1 activates ErbB4 and leads to a persistent hyperdopaminergic state in neonatal mice. These data prompted us to study the effect of peripheral administration of Nrg1 in the context of Parkinson's disease, a neurodegenerative disorder affecting the dopaminergic system in the adult brain. We observed that systemic injections of the extracellular domain of Nrg1ß(1) (Nrg1ß(1)-ECD) increased dopamine levels in the substantia nigra and striatum of adult mice. Nrg1ß(1)-ECD injections also significantly protected the mouse nigrostriatal dopaminergic system morphologically and functionally against 6-hydroxydopamine-induced toxicity in vivo. Moreover, Nrg1ß(1)-ECD also protected human dopaminergic neurons in vitro against 6-hydroxydopamine. In conclusion, we have identified Nrg1ß(1)-ECD as a neurotrophic factor for adult mouse and human midbrain dopaminergic neurons with peripheral administratability, warranting further investigation as therapeutic option for Parkinson's disease patients.