The dynamics of keratin expression in malignant transformation of cervical epithelium: a review.

OBJECTIVE: To review basic and clinical aspects of cytoskeletal keratin expression in normal cervical epithelia as well as in preneoplastic and malignant epithelia of the uterine cervix. DATA SOURCES: The results of extensive studies from our group and other groups on keratin phenotyping in normal premalignant and malignant cervical epithelia were summarized. METHODS OF STUDY SELECTION: All studies involving keratin expression in the cervix were reviewed, as were general studies on keratin expression in which the cervix was mentioned and studies relevant to understanding cervical cancer etiology (36 studies). DATA EXTRACTION AND SYNTHESIS: From these studies, keratin phenotypes of the various epithelia were derived. The phenotypes were correlated to existing theories on the development of cervical carcinoma.
CONCLUSIONS: It is possible to distinguish the various epithelial types in the normal cervix based on their keratin expression patterns. Reserve cells display a bidirectional keratin pattern, comprising keratins typical of both squamous and simple types of differentiation, reflecting the bipotential nature of these cells. Cervical intraepithelial neoplasia can be divided into two subpopulations, one characterized by the reserve cell keratin phenotype and the other by a keratin phenotype typical of nonkeratinizing squamous epithelia. The first population also contains the simple keratins, the relative percentage of which increases with increasing degree of dysplasia. We therefore suggest that these lesions are progressive in nature. Carcinomas show a differentiation-related keratin expression pattern in addition to the basic reserve cell keratin phenotype. Adenocarcinomas also have been shown to express most of the reserve cell keratins. The latter observation indicates a common progenitor for both carcinoma types.