Kandalam Mallikarjuna

Expression of Epidermal Growth Factor Receptor, Ezrin, Hepatocyte Growth Factor, and c-Met in Uveal Melanoma: An Immunohistochemical Study

The immunoreactivity of epidermal growth factor receptor (EGFR) ezrin, hepatocyte growth factor receptor (HGF), and c-Met was studied in 60 uveal melanomas and was correlated with clinicopathologic parameters. Metastases were diagnosed in the patients with uveal melanoma between 5 years and 8 years (median, 6.5 years) after enucleation. Using Kaplan-Meier statistical analysis, we found a significant association between high c-Met expression and death due to uveal melanoma (p < 0.03). EGFR was expressed in 18 of 60 (30%) tumors; ezrin was expressed in 30 of 60 (50%) tumors. Tumors with liver metastasis (n = 6) showed higher expression of c-Met (p = 0.0009) compared with the tumors with no extension/extrascleral extension without liver metastasis (groups A-45 and B-9). HGF was negative in all the six tumors that had liver metastasis. Further studies are required to understand the possible mechanism of ligand-independent c-Met activation in patients with uveal melanoma.

Comparative proteomic analysis of differentially expressed proteins in primary retinoblastoma tumors

Purpose: To understand the disease mechanism and to identify the potential tumor markers that would help in therapeutics, comparative proteomic analysis of 29 retinoblastoma (RB) tumors was performed using 14 non‐neoplastic retinas (age ranged from 45 to 89 years) as control tissues.

Expression of Insulin-Like Growth Factor Receptor (IGF-1R), c-Fos, and c-Jun in Uveal Melanoma: An Immunohistochemical Study

The immunoreactivity of insulin-like growth factor receptor type 1 (IGF-1R), c-Fos, and c-Jun by immunohistochemistry was studied in three groups of uveal melanomas and was correlated clinicopathologically. Immunoanalysis was correlated with cell types, largest tumor diameter, tumor-infiltrating lymphocytes, mitosis, nuclear grade, and extrascleral extension/liver metastasis. In group C (n = 6), tumors with liver metastasis showed higher expressions of IGF-1R (p = 0.0001), c-Fos (p = 0.004), and c-Jun (p = 0.018) compared with the tumors with no extension/extrascleral extension without liver metastasis (groups A-45 and B-9). Further studies are required to elucidate the role of sequential upregulation of these proteins and the transcriptional activity of c-Fos and c-Jun in uveal melanomas with liver metastasis.

Oxidative Stress in Retinoblastoma: Correlations with Clinicopathologic Features and Tumor Invasiveness

Purpose: Retinoblastoma (RB) is the most common primary intraocular malignancy of infancy and childhood, where tumor invasion into the choroid, optic nerve, and/or orbit are risk factors for metastasis. Here we have correlated oxidative stress with the clinicopathologic characteristics of retinoblastoma. Methods: Tumor samples were processed for histopathologic examination. Malondialdehyde, a biomarker of oxidative stress, was immunohistochemically analyzed in 34 archival retinoblastoma tumor specimens, which included 17 tumors that did not have any invasion of the choroid, optic nerve, and/or orbit, and another 17 tumors that had some form of invasion of the choroid, optic nerve, and/or orbit. Lipid peroxidation levels were biochemically measured in another cohort of retinoblastoma tissue samples (n = 16), and correlated clinicopathologically. Results: Malondialdehyde immunostaining was positive in all 34/34 (100%) tumors, and their corresponding clinicopathologic features were recorded. Malondialdehyde levels were significantly higher in tumors with invasion of the choroid, optic nerve, and orbit, when compared with tumors with no invasion (p < 0.05). No significant correlation was noted between malondialdehyde immunoreactivity and the differentiation/laterality of the tumors. Lipid peroxidation levels increased significantly in tumors with invasion of the choroid, optic nerve, and orbit than in tumors without invasion (p < 0.05). Conclusion: RB with invasion of the choroid, optic nerve, and/or orbit strongly correlates with increased oxidative stress.

CDKN1C (p57KIP2) mRNA expression in human retinoblastomas.

Purpose: Quantify cyclin dependent kinase inhibitor 1C (CDKN1C or p57KIP2) mRNA levels in human retinoblastoma tumors (RB) and associate with disease phenotype. Methods: CDKN1C mRNA expression was quantified in 55 RB, 3 retinoblastoma cell lines, and 12 control retinas by real time PCR. Localization of CDKN1C protein was confirmed by immunohistochemistry. Tumor CDKN1C expression levels were correlated with phenotype. Results: Fifty-three of 55 tumors showed significantly elevated levels of CDKN1C mRNA relative to age-matched or adult retina controls. No significant difference was seen relative to fetal retinal controls or retinoblastoma cell lines. Immunohistochemistry revealed heterogeneous staining of CDKN1C protein in tumor cells, which was mainly nuclear although some protein appeared to be cytoplasmic. No correlation was observed between the CDKN1C mRNA expression levels and tumor phenotype. Conclusion: High levels of CDKN1C expression are common in RB. It remains to be determined if elevated expression is a protective response to transformation, provides a selective advantage to tumor cells, or simply reflects the presence of dividing cells.