Comprehensive clinical imaging, histopathological analysis and liquid biopsy-based surveillance of human uveal melanoma in a prolonged rabbit xenograft model.

Uveal melanoma is the most common intraocular tumor in adults. Our group has previously developed a human uveal melanoma animal model; however, adverse effects caused by the immunosuppressive agent, cyclosporine A, prevented animals from surviving more than 12 weeks. In this study, we tested multiple cyclosporine A doses over an extended disease course up to 20 weeks, providing complete clinical imaging of intraocular tumors, histopathological analysis and liquid biopsy biomarker analysis. Twenty albino rabbits were divided into four groups with different daily cyclosporine A schedules (0-10 mg/kg) and inoculated with human uveal melanoma cell lines, 92.1 or MP41, into the suprachoroidal space. Rabbits were monitored with fundoscopy, ultrasound and optical coherence tomography. Intraocular tumors (macroscopic or microscopic) were detected in all study animals. Tumor size and growth were correlated to cyclosporine A dose, with tumors regressing when cyclosporine A was arrested. All tumors expressed HMB-45 and MelanA; however, tumor size, pigmentation and cell morphology differed in 92.1 vs. MP41 tumors. Finally, across all groups, circulating tumor DNA from plasma and aqueous humor was detected earlier than tumor detection by imaging and correlated to tumor growth. In conclusion, using three clinically relevant imaging modalities (fundoscopy, ultrasonography and optical coherence tomography) and liquid biopsy, we were successfully able to monitor tumor progression in our rabbit xenograft model of human uveal melanoma.

Analysis of HSP90 Expression Is Valuable in the Differential Diagnosis of Ocular Surface Squamous Lesions.

OBJECTIVES: The aim of this study was to evaluate heat shock protein 90 (HSP90) expression in squamous lesions (SLs) and to assess its diagnostic value for different lesions within the SL spectrum. METHODS: A total of 70 conjunctival SLs, including 19 papillomas, 22 cases of conjunctival intraepithelial neoplasia (ConINs) I, 11 cases of ConIN II, six cases of ConIN III, and 12 squamous carcinomas (sqCAs), were evaluated using the German immunoreactive score against HSP90. RESULTS: Cytoplasmic HSP90 expression differed between low- and high-grade lesions (P < .001). Among high-grade lesions, the nuclear HSP90 score was higher in the ConIN III-sqCA group than in the ConIN II group (P = .0162). A percentage of total thickness staining of less than 73% differentiated between ConIN III and sqCA. CONCLUSIONS: The expression of HSP90 is particularly useful to differentiate low-grade from high-grade lesions of the conjunctiva. HSP90 may play an important role in the malignant transformation of SLs and could be a new target for therapy.