Cytokeratins of normal epithelia and some neoplasms of the female genital tract.

Cytokeratins are a family of polypeptides of intermediate filaments which in diverse epithelia are expressed in different, yet specific, combinations. We have studied the cytokeratins present in normal epithelia of the female genital tract, in comparison with those present in genital tract carcinomas, by two-dimensional gel electrophoresis of cytoskeletal proteins from microdissected tissues and by immunofluorescence microscopy. Cells of ovarian mesothelium, oviduct, endometrium, and endocervix contain cytokeratin polypeptides nos. 7, 8, 18, and 19. By contrast, tonofilaments of the stratified squamous epithelia of vagina and exocervix contain cytokeratins 4, 5, 6, 13, 14, 15, 16, and 19. Exocervical regions distant from the endo-exocervical junction as well as vagina contain, in addition, the large (Mr 68,000) and basic cytokeratin component no. 1, previously described in epidermis. Endocervical squamous metaplasia at the endo-exocervical border displays a complex cytokeratin pattern, probably due to cell-type heterogeneity. Similar cytokeratin patterns are also observed in genital tract epithelia of the cow and mouse. In human carcinomas of the female genital tract, two main types of cytokeratin patterns can be distinguished. Ovarian carcinomas and endometrial adenocarcinomas express cytokeratins 7, 8, 18, and 19 and, thus, maintain the pattern of the cells of their origin. In endocervical adenocarcinomas the additional presence of component no. 17 has been noted. Nonkeratinizing squamous cell carcinomas of the cervix show a very complex pattern (cytokeratins 5, 6, 7, 8, 13, 14, 15, 17, 18, and 19). Keratinizing squamous cell carcinomas of the cervix display lower complexity and lack cytokeratins 7, 8, and 18. When frozen sections are examined by immunofluorescence microscopy, all epithelia of the genital tract are stained with the monoclonal cytokeratin antibody KG 8.13. Simple epithelia but not the stratified epithelia of vagina and exocervix also react with monoclonal antibodies specific for cytokeratins 8 or 18. The value of cytokeratin polypeptide patterns in distinguishing diverse epithelial cell types of the female genital tract, in elucidating the histogenesis of neoplasms, and in providing a new tool for the differential diagnosis of tumors is discussed.