Molecular Detection of Noninvasive and Invasive Bladder Tumor Tissues and Exfoliated Cells by Aberrant Promoter Methylation of Laminin-5 Encoding Genes

摘要: Laminin-5 (LN5) anchors epithelial cells to the underlying basement membrane, and it is encoded by three distinct genes: LAMA3, LAMB3, LAMC2. To metastasize grow, cancer must invade destroy membrane. Our previous work has shown that epigenetic inactivation a major mechanism of silencing LN5 genes in lung cancers. We extended our methylation studies resected bladder tumors (n = 128) exfoliated cell samples (bladder washes voided urine; n 71) correlated data with clinicopathologic findings. Nonmalignant urothelium had uniform expression lacked methylation. The frequencies for were 21-45%, there was excellent concordance between corresponding cells. Methylation LAMA3 LAMB3 index significantly several parameters poor prognosis (tumor grade, growth pattern, muscle invasion, tumor stage, ploidy pattern), whereas LAMC2 associated shortened patient survival. Of particular interest, helped distinguish invasive (72%) from noninvasive (12%) tumors. These results suggest potential clinical applications