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Clinico-pathological correlations of fatty acid synthase expression in retinoblastoma: an Indian cohort study.

Abstract：

:Retinoblastoma (RB), the most common intra-ocular malignancy in children under 5 years of age, has an estimated incidence of about 2000 a year in India, where most cases are in advanced stage at the time of diagnosis. Newer therapeutic approaches would reduce the morbidity of chemotherapy in children with RB. Fatty Acid Synthase (FASN), a lipogenic multi-enzyme complex, is minimally expressed in normal human tissues and over expressed in many cancers, making it an attractive target for cancer therapy. We analyzed RB tissues for FASN protein expression by immunohistochemistry, western blot, and ELISA, and FASN mRNA expression by RT-PCR. FASN expression was correlated with the clinico-pathological characteristics of the tumors. FASN immunostaining was positive in all the 44 RB tissues analyzed (100%). However, FASN expression was heterogeneous within the tumor samples. Tumors with invasion of choroid, optic nerve, orbit and/or retinal pigment epithelium showed significantly higher FASN immunoreactivity than the tumors without invasion (P<0.05), supported by western analysis (P<0.05). FASN expression was significantly high in poorly differentiated retinoblastomas (P<0.05). FASN protein and FASN mRNA estimated by ELISA and RT-PCR respectively showed multi-fold expression over the non-neoplastic muller glial cells that varied quantitatively between tumor tissues. FASN mRNA over-expression was substantially lower than the corresponding FASN protein expression values. The present study reports (i) markedly high expression of FASN protein in poorly differentiated and in invasive retinoblastomas, and (ii) multi-fold over-expression of FASN mRNA and protein in RB tissues, although at varying levels, indicating FASN to be a potential therapeutic target in retinoblastoma management.

journal_name

Exp Mol Pathol

journal_title

Experimental and molecular pathology

authors

Vandhana S,Deepa PR,Jayanthi U,Biswas J,Krishnakumar S

doi

10.1016/j.yexmp.2010.11.007

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

29-37

issue

eissn

0014-4800

issn

1096-0945

pii

S0014-4800(10)00161-9

journal_volume

pub_type

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Clinico-pathological correlations of fatty acid synthase expression in retinoblastoma: an Indian cohort study.