Expression and prognostic value of CD44 standard and variant v3 and v6 isoforms in prostate cancer

Abstract

Background: The adhesion molecule CD44 standard (CD44s), and its variant isoforms v3 and v6 are associated with cell-to-cell adhesion. The down-regulation of CD44 standard and its variant isoform CD44v6 is linked with early cancer cell dissemination, but the relationship between CD44v3 and malignant features of prostate cancer (PC) has not been established previously.

Methods: The expression of CD44s and its CD44v3 and CD44v6 isoforms was analysed by immunohistochemistry in 209 archival PC biopsy specimens to establish their prognostic value.

Results: Down-regulation of CD44s and CD44v6 was related to high T classification, metastasis, high Gleason score, DNA aneuploidy, high S-phase fraction, high mitotic index, perineural growth and dense amount of tumour infiltrating lymphocytes (p < 0.03 for all). Down-regulation of CD44s and CD44v6 was related to poor survival in the entire cohort (p < 0.0001), in M0 tumours (p < 0.001) and in T1-2M0 tumours (p < 0.05). In needle biopsies and TURP specimens, the prognostic impact of the investigated parameters was similar. In the multivariate analysis, T classification (p = 0.0009), presence of metastases (p < 0.0001), Gleason score (p = 0.0060) and CD44v6 (p = 0.0220) expression were independent prognostic factors. In M0 tumours, T classification (p < 0.0001) and CD44v6 (p = 0.003) independently predicted survival.

Conclusion: Down-regulation of CD44s and its CD44v6 isoform is related to tumour malignancy and unfavourable prognosis in PC.