Up-regulation of CD44 variant exon expression in endometrial carcinomas: analysis of mRNA and protein isoforms, and relation to clinicopathological factors.

In order to clarify the relation between expression of individual CD44 variant exons and tumor progression, 34 endometrial carcinomas (endometrioid type) were investigated, as well as 27 samples of normal endometrium, using a combination of reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridization (SBH). Western blotting was also performed for comparison of protein levels with the results of the RT-PCR/SBH methods. Analysis of gross CD44 splicing patterns demonstrated high-level expression of variant isoforms in endometrial carcinomas as compared with normal endometrium. Exon-specific RT-PCR/SBH assays revealed large, abundant transcripts of individual variant exons in particular v3, v4, and v5, in tumors, but these isoforms were also expressed in normal endometria, suggesting a lack of tumor-specificity. No individual CD44 variant transcripts were associated with any of the prognostic factors investigated. Parallel observations showed variant CD44 transcripts to be more readily detectable than protein isoforms in the same samples. These findings indicate that in endometrial carcinomas, expression of individual variant CD44 exons is markedly up-regulated, but this molecule may not be useful as a consistent indicator of tumor progression.