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

To clarify the possible role of CD44 in the development or progression of u terine cervical tumours, an immunohistochemical investigation was carried o ut on 125 cases of cervical intraepithelial neoplasia (CIN), 78 invasive sq uamous cell carcinomas (ISCC), 61 cervical adenocarcinomas (AC), nine adeno squamous carcinomas (ASq), and 15 carcinomas with co-existent SCC and AC co mponents, as well as 87 samples of normal cervix. A combination of reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridiz ation (SBH) was also applied to 16 cervical carcinomas and 24 normal cervic al specimens. Immunoreactivity for CD44s, CD44v3, and CD44v6 did not alter during the progression of CIN, while significantly decreased expression was observed in ISCC, associated,vith invasive features in some tumours. Reduc ed levels of CD44 expression in AC were also found, compared with normal ce rvical glandular epithelia. The average immunoreactivity scores for CD44s, CD44v3, and CD44v6 were significantly higher in ISCC than in AC, in line wi th the RT-PCR/SBH assay results. However, CD44 scores did not correlate wit h any clinicopathological factors or with survival in ISCC or AC. The ASq a nd AC CD44 scores were similar, while staining patterns in mixed tumours we re dependent on the morphological phenotype, suggesting a close association between CD44 expression and the cell types. The results suggest that where as CD44 is down-regulated during cervical tumourigenesis, positivity may no t be useful as a consistent prognostic indicator. Copyright (C) 1999 John W iley & Sons, Ltd.