Expression of the p53 homologue p63 in early cervical neoplasia

Background. p63, a homologue of the tumor suppressor gene p53, is expressed in embryonic, adult murine, and human basal squamous epithelium and encode s both transactivating and dominant negative transcript isoforms. Mouse emb ryos functionally deficient in p63 fail to replenish basal squamous epithel ial cells, resulting in multiple defects that include absent genital squamo us epithelium. This study investigated the expression of p63 in the human c ervical transformation zone and early cervical neoplasia. Methods. Tissue localization of p63 was determined by immunohistochemistry in a wide range of epithelia. A correlation was also made between p63 expre ssion and squamous basal cell (keratin 14), endocervical columnar cell (muc icarmine), and cell-cycle specific (Ki-67) markers. Results. p63 expression by immunostaining delineated basal and parabasal ce lls of maturing ectocervical squamous mucosa, squamous metaplasia in the ce nix, and basal and subcolumnar cells of the cervical transformation zone. I n atrophic epithelia immunostaining for p63 was present in all cell strata. In early cervical neoplasia, p63 expression was inversely correlated with both squamous cell maturation and nonsquamous differentiation in GIN. This biomarker also identified basal cells in a subset of preinvasive cervical n eoplasms with endocervical cell differentiation that were bcl-2 and keratin 14 negative. Conclusions. In the lower female genital tract, p63 is preferentially expre ssed in immature cells of squamous lineage and is not Linked to cell prolif eration. The broader range of p63 expression relevant to keratin 14 and bcl -2 indicates that p63 may identify additional subsets of benign and neoplas tic epithelial basal cells in the cervical transformation zone and may be u seful in studying cell differentiation in the early stages of neoplastic ch ange in this region. (C) 2001 Academic Press.