BCL-2 immunoreactivity increases with severity of CIN: a study of normal cervical epithelia, CIN, and cervical carcinoma.

The presence of the BCL-2 protein, a marker for inhibition of programmed cell death, was studied in a series of routinely processed cervical tissues, consisting of normal endocervical (n = 40) and ectocervical epithelium (n = 27), squamous metaplastic epithelium (n = 30), CIN (cervical intraepithelial neoplasia) lesions (n = 32), and cervical carcinomas (n = 13). BCL-2 was strongly expressed in the basal cell compartment of normal ectocervical squamous epithelium and in nearly all reserve cells, while in endocervical columnar cells it was moderately expressed. In immature squamous metaplastic epithelium, BCL-2 expression varied. Half of the cases showed only basal cell staining, while the other half showed staining also in suprabasal layers. BCL-2 could be detected in all premalignant lesions, showing a striking increase in the number of positive cells with increasing severity of CIN, in combination with a mild increase in staining intensity. All adenocarcinomas were positive (n = 5), while five of eight squamous cell carcinomas expressed BCL-2. Based on these results, it is hypothesized that both the larger number of cells staining with BCL-2 in higher grades of CIN and the increase in staining intensity imply an increasing protection of these neoplastic conditions against programmed cell death. This protection facilitates not only continuing proliferation, but also the induction of genetic instability in dysplastic epithelial cells; it may thus reflect the greater capacity of the more severe CIN lesions to evolve into cervical carcinoma.