Can keratin 8 and 17 immunohistochemistry be of diagnostic value in cervical cytology? A feasibility study

Based on results from evaluation of tissue sections from premalignant lesions of the uterine cervix, the authors examined the hypothesis that immunostaining of Papanicolaou-stained cytologic smears with monoclonal antibodies to keratins 8 and 17 allows detection of cervical intraepithelial neoplasia (CIN) with progressive potential. They also investigated whether detection of these two keratin subtypes could be of help in the analysis of normal and/or poor quality cytology smears.

Sixty-one Papanicolaou-stained smears, representing 25 normal smears, 8 CIN 1, 7 CIN 2, 18 CIN 3, and 3 cervical carcinomas, were stained with CAM 5.2 and E3, which are capable of detecting keratin 8 and 17, respectively. The percentages of immunoreactive normal, metaplastic, dysplastic, and malignant epithelial cells were determined.

In normal cervical smears, keratin 8 was detected in endocervical columnar cells and sporadically in immature squamous metaplastic cells. Keratin 17 was identified in reserve cells and frequently in immature squamous metaplasic cells. In CIN, the number of cases in which keratin 8 was present increased with the severity of the lesion. Keratin 17 was found in the majority of CIN lesions, irrespective of grade. Intensity of immunostaining and number of cells stained per lesion varied and were also not related to the severity of CIN.

The use of the keratin 8 antibody in normal cervical smears enabled the detection of endocervical cells in cases where they were thought to be absent, particularly in cases with severe inflammation. Staining with keratin 17 enabled the identification of reserve cells or immature metaplastic cells, which were often misinterpreted as parabasal cells. The application of antibodies to these subtypes of keratins in cervical cytology can to a certain extent help in the identification of CIN and may in future be tested in automated screening.