Lymphoid Enhancing Factor-1(lef-1) Gene Mutation in Eyelid Sebaceous Carcinoma
Perumal Jayaraj, Seema Sen, Arvind Rai, Kunzang Chosdol, Anjana Sharma, Seema Kashyap, Neelam Pushker. AIIMS, New Delhi, India; NCDC, Delhi, India
Background: A higher incidence of Eyelid Sebaceous carcinoma (ESC) is reported from China and India. The molecular mechanisms underlying pathogenesis of ESC are not known.β-catenin signaling pathway has a role in the normal development of sebaceous glands; Lef-1(Lymphoid enhancing factor-1) gene is a key transcription factor and binding partner of β-catenin molecules within the nucleus. Mutations of Lef-1 have been described in transgenic mice models which lead to spontaneous skin tumors with sebaceous differentiation. The present study was therefore undertaken to determine the role of Lef-1 in the pathogenesis of ESC.
Design: Thirty-six cases of histopathological confirmed ESC diagnosed between2007-2010 were selected for this study. Fresh tissues were obtained after informed consent and Institute Ethical Committee approval. Lef-1 immunoexpression using monoclonal antibodies against Lef-1 clone (EP2030Y), at a dilution of (1:50) was evaluated on formalin fixed paraffin embedded sections. Mutational analysis of Lef-1(exon-1, which encodes the β-catenin binding domain) was undertaken by sequencing PCR.The results were correlated with the clinicopathological features.
Results: Loss of immunohistochemical expression of Lef-1 was present in 69% cases (25/36) and Lef-1 mutations in exon-1 were observed in 19% cases (7/36). All 7 samples showed non-sense mutations at codon(27) resulting in amino acid change AAG(Lysine)→TAG (stop).
(figure1a shows wild sequence chromatogram and figure1b mutated allele).
All the cases harboring the Lef-1 mutations were also negative for Lef-1 expression.6/7 ESC patients with lef-1 mutation had advanced age(> 60 years), 4/7 were females, upperlid was involved in all and 5/7 had tumor size≥ 2cm as well as poor histologic differentiation.There was no significant correlation of Lef-1 mutation with any of the clinicopathological features.
Conclusions: This preliminary study suggests the possible role of Lef-1 mutations in the molecular pathogenesis of Eyelid Sebaceous Carcinoma.However, further studies are needed to elucidate the exact role of Lef-1/β catenin signalling pathway in it's pathogenesis.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 315, Wednesday Afternoon