Cytological screening for cervical cancer or its precursors using Papanicolaou's smear test (Pap test) has been highly efficient to reduce the morbidity and mortality of cervical cancer. However, evaluation of the Pap test relies on subjective diagnostic parameters and is affected by a high rate of false-positive and false-negative results. More objective diagnostic parameters to identify truly dysplastic or neoplastic cells in cervical smears as well as in cervical biopsy samples would therefore avoid insecurity for many patients and the high screening costs associated with repeated testing. Cervical dysplasia is induced by persistent infections through highrisk types of human papillomaviruses (HPVs). Outgrowth of dysplastic lesions is triggered by increasing expression of two viral oncogenes, E6 and E7, which both interact with various cell cycle-regulating proteins. Among these is the retinoblastoma gene product pRB, which is inactivated by E7. pRB inhibits transcription of the cyclin-dependent kinase inhibitor gene p16 INK4a . Increasing expression of the viral oncogenes in dysplastic cervical cells might thus be reflected by increased expression of p16 INK4a . In line with this hypothesis, we observed marked overexpression of p16 INK4a in all cervical intraepithelial neoplasm (CIN) I lesions (n ‫؍‬ 47) except those associated with low-risk HPV types (n ‫؍‬ 7), all CIN II lesions (n ‫؍‬ 32), all CIN III lesions (n ‫؍‬ 60) and 58 of 60 invasive cervical cancers. In contrast, no detectable expression of p16 INK4a was observed in normal cervical epithelium (n ‫؍‬ 42), inflammatory lesions (n ‫؍‬ 48) and low-grade cervical lesions (CIN I) associated with low-risk HPV types (n ‫؍‬ 7). Dysplastic cells could also be identified in cervical smears using a specific p16 INK4a monoclonal antibody. These data demonstrate that p16 INK4a is a specific biomarker to identify dysplastic cervical epithelia in sections of cervical biopsy samples or cervical smears.

In several studies, attempts were made to establish criteria for distinguishing malignant Brenner tumors from proliferating and low malignant potential ones. Although these criteria can be applied to the majority of cases, there still exist tumors that present problems in classification. In applying the World Health Organization (WHO) criteria for Brenner tumors, the most important feature for distinguishing the intermediate forms from the malignant ones is the presence of stromal invasion in the latter. This feature has generally been considered difficult to employ because of the fundamental fibroepithelial nature of Brenner tumors, the stroma being derived from the ovarian stroma. A logical and relatively easily applicable classification of Brenner tumors is presented in this report. Although more complex than the WHO classification, it includes newly recognized variants of the Brenner tumor and avoids using the same terminology to describe different types and degrees of epithelial abnormalities. Fourteen unusual Brenner tumors were studied, intermediate between typical benign and frankly malignant ones, and were classified into 3 categories representing progressive epithelial abnormalities. These include metaplastic, proliferating, and tumors of low malignant potential. In none of these does stromal invasion occur. Each of these categories corresponds to a particular urothelial abnormality or neoplasm. Through this classification, a better understanding of the morphology and biologic behavior of unusual types of Brenner tumors can be expected.

No abstract