Altered Expression of CD44 and Variant Isoforms in Human Adenocarcinoma of the Endocervix during Progression

Abstract

Objective. Altered expression of the CD44 family of cell adhesion molecules has been associated with tumor progression and metastasis. The aim of this study was to investigate the expression of the gene products of CD44 standard (CD44s) and several alternatively spliced variants (CD44v4, v6, v7, and v9) in adenocarcinoma of the endocervix and to correlate the degree of their expression with disease progression.Methods. Immunohistochemical staining for CD44s and CD44v4, v6, v7, and v9 was performed on formalin-fixed, paraffin-embedded endocervical specimens. Seventeen cases of adenocarcinoma in situ (AIS) and 22 cases of invasive adenocarcinoma of the endocervix were included in this study, and the immunoreactivity was compared with that of normal endocervical epithelium.Results. (1) In the normal endocervical mucosa, immunoreactivity for CD44s and the splice variants was lacking or was confined to only the basal portion of the glandular epithelium along the basement membrane; (2) CD44s was diffusely expressed along the entire cytoplasmic membrane, including the luminal surface of the tumorous glands in 94% of AIS and 95% of invasive adenocarcinomas; (3) a significantly stronger expression of CD44s was observed in invasive adenocarcinomas than in AIS; (4) in contrast to all other splice variants, CD44v9 demonstrated an increased expression in nearly all in situ and invasive lesions compared to the normal tissue; (5) CD44v4 and v6 were expressed only in a small proportion of invasive adenocarcinomas and were near totally absent in the in situ lesions; and (6) CD44 v7 was totally absent in all normal, in situ, and invasive lesions studied.Conclusions. It appears that neoplastic transformation of endocervical epithelium is associated with qualitative and quantitative changes in the expression of CD44 standard molecule and some CD44 splice variants.