Altered gene expression in conjunctival squamous cell carcinoma

Alka Mahale, Hind Alkatan, Saeed Alwadani, Maha Othman, Maria J. Suarez, Antoinette Price, Hailah Al-Hussain, Sabah Jastaneiah, Wayne Yu, Azza Maktabi, Edward P. Deepak, Charles G. Eberhart, Laura Asnaghi

Research output: Contribution to journalArticlepeer-review

Abstract

Conjunctival squamous cell carcinoma is a malignancy of the ocular surface. The molecular drivers responsible for the development and progression of this disease are not well understood. We therefore compared the transcriptional profiles of eight snap-frozen conjunctival squamous cell carcinomas and one in situ lesion with normal conjunctival specimens in order to identify diagnostic markers or therapeutic targets. RNA was analyzed using oligonucleotide microarrays, and a wide range of transcripts with altered expression identified, including many dysregulated in carcinomas arising at other sites. Among the upregulated genes, we observed more than 30-fold induction of the matrix metalloproteinases, MMP-9 and MMP-11, as well as a prominent increase in the mRNA level of a calcium-binding protein important for the intracellular calcium signaling, S100A2, which was induced over 20-fold in the tumor cohort. Clusterin was the most downregulated gene, with an approximately 180-fold reduction in the mRNA expression. These alterations were all confirmed by qPCR in the samples used for initial microarray analysis. In addition, immunohistochemical analysis confirmed the overexpression of MMP-11 and S100A2, as well as reductions in clusterin, in several independent in situ carcinomas of conjunctiva. These data identify a number of alterations, including upregulation of MMP-9, MMP-11, and S100A2, as well as downregulation of clusterin, associated with epithelial tumorigenesis in the ocular surface.

Original languageEnglish (US)
Pages (from-to)452-460
Number of pages9
JournalModern Pathology
Volume29
Issue number5
DOIs
StatePublished - May 1 2016

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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