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

Ubaradka G. Sathyanarayana, Riichiroh Maruyama, Asha Padar, Makoto Suzuki, Jolanta Bondaruk, Arthur I Sagalowsky, John D Minna, Eugene P Frenkel, H. Barton Grossman, Bogdan Czerniak, Adi F Gazdar

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)1425-1430
Number of pages6
JournalCancer research
Volume64
Issue number4
DOIs
StatePublished - Feb 15 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Sathyanarayana, U. G., Maruyama, R., Padar, A., Suzuki, M., Bondaruk, J., Sagalowsky, A. I., Minna, J. D., Frenkel, E. P., Grossman, H. B., Czerniak, B., & Gazdar, A. F. (2004). Molecular Detection of Noninvasive and Invasive Bladder Tumor Tissues and Exfoliated Cells by Aberrant Promoter Methylation of Laminin-5 Encoding Genes. Cancer research, 64(4), 1425-1430. https://doi.org/10.1158/0008-5472.CAN-03-0701