Antibodies against tissue polypeptide antigen (TPA) and keratins of high molecular weight (62-67 kD) were used to indicate different stages of cell differentiation. The immunohistochemical study was carried out by indirect immunofluorescence. In dysplasia, particularly in CIN grades II to III, TPA labeling comprised not only basal layer cells (as seen in normal mucosa) but more superficial layers as well. Expression of keratins of high molecular weight was reduced to small foci of keratinization and scattered dyskeratotic cells. In typical small cell anaplastic carcinoma in situ, TPA antibodies were observed to label all epithelial cell layers. There was no reactivity with antibodies against keratins of high molecular weight. In invasive cancer, TPA staining was closely related to the degree of maturation. Nonkeratinized tumor zones were entirely labeled by TPA antibodies, whereas keratinized tumor foci were negative for TPA except for peripheral tumor cell layers. In invasive cancer, keratins of high molecular weight were restricted to differentiated portions of the tumor. Our immunohistochemical findings support the present concepts of TPA (as a member of the heterogeneous keratin family) as an indicator of cell differentiation. Immunohistochemical demonstration of keratins of different molecular weight offers a method of assessing squamous differentiation at the cervical transformation zone and in cervical cancer and precancer.
