Down-regulation of CD44 standard and variant isoforms during the development and progression of uterine cervical tumours.

Abstract

To clarify the possible role of CD44 in the development or progression of uterine cervical tumours, an immunohistochemical investigation was carried out on 125 cases of cervical intraepithelial neoplasia (CIN), 78 invasive squamous cell carcinomas (ISCC), 61 cervical adenocarcinomas (AC), nine adenosquamous carcinomas (ASq), and 15 carcinomas with co-existent SCC and AC components, as well as 87 samples of normal cervix. A combination of reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridization (SBH) was also applied to 16 cervical carcinomas and 24 normal cervical specimens. Immunoreactivity for CD44s, CD44v3, and CD44v6 did not alter during the progression of CIN, while significantly decreased expression was observed in ISCC, associated with invasive features in some tumours. Reduced levels of CD44 expression in AC were also found, compared with normal cervical glandular epithelia. The average immunoreactivity scores for CD44s, CD44v3, and CD44v6 were significantly higher in ISCC than in AC, in line with the RT-PCR/SBH assay results. However, CD44 scores did not correlate with any clinicopathological factors or with survival in ISCC or AC. The ASq and AC CD44 scores were similar, while staining patterns in mixed tumours were dependent on the morphological phenotype, suggesting a close association between CD44 expression and the cell types. The results suggest that whereas CD44 is down-regulated during cervical tumourigenesis, positivity may not be useful as a consistent prognostic indicator.