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A. C. Schefler, S. R. Dubovy, D. T. Tse, A. S. Hackam; Exploration of Wnt pathway Gene Expression in Sebaceous Carcinoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5696.
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Sebaceous carcinoma is a malignant neoplasm that arises from the Meibomian glands, the glands of Zeis, and the sebaceous glands of the caruncle. Compared to other tumors of the ocular adnexae, sebaceous carcinoma is often detected at late stages and is difficult to treat because of its propensity for pagetoid spread. As a result, an intralesional injectable targeted therapy would be particularly beneficial in this disease. However, there is limited information about the molecular pathogenesis of sebaceous carcinoma. In this study, we explored expression patterns for genes encoding for ligands that stimulate the Wnt pathway, a signaling cascade implicated in many cancers. The objective was to define the gene expression profile for sebaceous carcinoma tissue compared to matched control tissue in order to identify potential Wnt-related targets for therapy.
Paraffin-embedded tumor specimens of patients previously diagnosed with sebaceous carcinoma were obtained from tissue blocks. Fibrovascular stroma from adjacent lid tissue served as matched controls. Tumor tissue was deparaffinized and total RNA was isolated. Expression of Wnt genes in both sebaceous carcinoma tissue and control tissue was examined. Expression of genes encoding for ligands that stimulate the Wnt pathway were examined by reverse transcriptase polymerase chain reaction (RTPCR). Results were confirmed with multiple patient specimens and by immunohistochemistry.
Expression of inhibitors of the Wnt pathway such as WIF1 and Axin1 was present in the tumor tissue to an equivalent degree or more than the control tissue. Expression of Wnt pathway genes known to function as tumor suppressors such as Wnt5A were absent in the tumor and the control tissue. Expression of beta-catenin, which results in expression of Wnt target genes, was absent in the tumor tissue but present in the control tissue. Confirmation of these results with immunohistochemical staining is ongoing.
Formalin-fixed paraffin embedded sebaceous carcinoma samples suggest antagonized Wnt signaling and possible downregulation of beta-catenin in ths disease. These findings are consistent with previous results in transgenic mice with skin tumors of a sebaceous phenotype and with similar results demonstrated by our group in retinoblastoma. Continued exploration of the role of the Wnt pathway in this disease will offer insight into sebaceous carcinoma pathogenesis and will provide a practical foundation for the future development of targeted drug therapy.
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