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In Vivo and In Vitro "Markers" of Human Cervical Intraepithelial Neoplasia¹

Department of Obstetrics and Gynecology, Rush Medical College, Rush University, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612

The human uterine cervix offers a unique opportunity to study the early lesions of squamous cell carcinoma, i.e., carcinoma in situ and dysplasia [combined as cervical intraepithelial neoplasia (CIN)]. In vivo, the patients with CIN have the epidemiological common denominators or "markers" of early onset of coitus, multiple sexual partners, 1st delivery before age 20, and antibodies to herpes simplex virus type 2 more frequently than do controls. The lesions themselves have specific epithelial and vascular changes observable with the colposcope in addition to the usual histological markers from biopsy specimens. The chromosomes and DNA content of cells in these lesions are abnormal. In vitro, the cells from CIN have characteristics somewhat between normal and invasive carcinoma. They lack contact inhibition and may be transferred for several generations, in contrast to normal cervical epithelial cells. The fibroblasts from areas adjacent to CIN are different from normal fibroblasts. The mitotic mechanism in cells cultured from CIN has a significantly prolonged prophase and telophase when compared to similar normal cells. The surface of CIN cells, unlike normal cells, has numerous microvilli when examined by scanning electron microscopy and has characteristic differences from normal cells with numerous elongated, irregular microvilli. With the transmission electron microscope, an increase in microvilli and a decrease in desmosomes and tonofibrils are seen in CIN cells. Some of these markers are being used clinically to manage patients with CIN. Other markers are the basis for further investigation of human carcinogenesis.

¹ Presented at the Conference "Early Lesions and the Development of Epithelial Cancer," October 21 to 23, 1975, Bethesda, Md. Supported in part by a grant from the American Cancer Society, Illinois Division.