PurposeTo correlate the differentially expressed miRNAs with clinico-pathological features in uveal melanoma (UM) tumors harbouring chromosomal 3 aberrations among South Asian Indian cohort.MethodsBased on chromosomal 3 aberration, UM (n = 86) were grouped into monosomy 3 (M3; n = 51) and disomy 3 (D3; n = 35) by chromogenic in-situ hybridisation (CISH). The clinico-pathological features were recorded. miRNA profiling was performed in formalin fixed paraffin embedded (FFPE) UM samples (n = 6) using Agilent, Human miRNA microarray, 8x15KV3 arrays. The association between miRNAs and clinico-pathological features were studied using univariate and multivariate analysis. miRNA-gene targets were predicted using Target-scan and MiRanda database. Significantly dys-regulated miRNAs were validated in FFPE UM (n = 86) and mRNAs were validated in frozen UM (n = 10) by qRT-PCR. Metastasis free-survival and miRNA expressions were analysed by Kaplen-Meier analysis in UM tissues (n = 52).ResultsUnsupervised analysis revealed 585 differentially expressed miRNAs while supervised analysis demonstrated 82 miRNAs (FDR; Q = 0.0). Differential expression of 8 miRNAs: miR-214, miR-149*, miR-143, miR-146b, miR-199a, let7b, miR-1238 and miR-134 were studied. Gene target prediction revealed SMAD4, WISP1, HIPK1, HDAC8 and C-KIT as the post-transcriptional regulators of miR-146b, miR-199a, miR-1238 and miR-134. Five miRNAs (miR-214, miR146b, miR-143, miR-199a and miR-134) were found to be differentially expressed in M3/ D3 UM tumors. In UM patients with liver metastasis, miR-149* and miR-134 expressions were strongly correlated.ConclusionUM can be stratified using miRNAs from FFPE sections. miRNAs predicting liver metastasis and survival have been identified. Mechanistic linkage of de-regulated miRNA/mRNA expressions provide new insights on their role in UM progression and aggressiveness.

Background: The tumour microenvironment (TME) consisting of tumour cells and multiple stromal cell types regulate tumour growth, invasion and metastasis. While the concept of TME and presence of stromal cellular components is widely established in cancers, its significance in the paediatric intraocular malignancy, retinoblastoma (RB), remains unknown. Methods: The study qualitatively identified the presence of multiple stromal cellular subtypes in RB TME by immunohistochemistry. Results: Results of the study identified the presence of stromal cell types such as endothelial cells, tumour-associated macrophages, fibroblasts, cancer-associated fibroblasts, retinal astrocytes and glia in RB TME. The extent of stromal marker positivity, however, did not correlate with histopathological features of RB. Conclusions: The findings of the study convincingly suggest the presence of a stromal component in RB tumours. The interactions between stromal cells and tumour cells might be of profound importance in RB progression.

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