miR-196b-5p and miR-107 expression differentiates ocular sebaceous carcinoma from squamous cell carcinoma of the comjunctiva

Ocular Sebaceous Carcinoma (OSC) is a rare malignant tumor for which initial clinical and pathological diagnosis is often incorrect. OSC can mimic Squamous Cell Carcinoma of the Conjunctiva (SCCC). Aim of this study was to find microRNA biomarkers to distinguish OSC and SCCC from normal tissue and from each other. Clinical OSC and SCCC case files and corresponding histopathological slides were collected and reviewed. Microdissected formalin-fixed paraffin-embedded tumor and control tissue were sub-jected to semi-high throughput microRNA profiling. MicroRNA expression distinguishes OSC and SCCC from corresponding control tissues. Selected differentially expressed miRNAs were validated using single RT-PCR assays. No prognostic miRNAs could be identified that reliable predict SCCC metastasis or OSC recurrence. A com-parison between OSC (n=14) and SCCC (n=18) revealed 38 differentially expressed microRNAs (p<0.05). Differentially expressed miRNAs were selected for validation in the discovery cohort and an independent validation cohort (OSC, n=11; SCCC, n=12). At least two miRNAs miR-196b-5p (p ≤ 0.05) and miR-107 (p ≤ 0.001) displayed a statistically significant differential expression between OSC and SCCC with miR-196b-5p upregulated in SCCC and miR-107 up-regulated in OSC. In the validation cohort microRNA miR-493-3p also showed significant up-regulation in SCCC when compared to OSC (p ≤ 0.05). ROC analyses indicated that the com-bined miR-196b-5p and miR-107 expression levels predicted OSC with 90.0% sensitivity and 83.3% specificity. In conclusion, combined testing of miR-196b-5p and miR-107, can be of additional use in routine diagnostics to discriminate OSC from SCCC. MicroRNA expression profiles were determined from archival formalin-fixed paraffin-embedded (FFPE) tumor samples of ocular sebaceous carcinoma (OSC, n=14); squamous cell carcinoma of the conjunctiva (SCCC, n=18) and control tissues Meibomian gland tissue (n=6, control to OSC); conjunctival squamous epithelium of the eyelid (n=6; control to SCCC). TaqMan® Low Density Array (TLDA) Human MicroRNA Cards (A card v2.0, Applied Biosystems/Thermo Fisher Scientific) were used. The microRNA expression profiling data was used for a comparison between OSC and corresponding control tissue, between SCCC and corresponding control tissue, between OSC and SCCC, between primary OSC that eventually exhibit recurrence or no recurrence and between SCCC that eventually exhibit metastasis or no metastasis.