Association between cervical neoplasia and apoptosis as detected by in situ nuclear labeling.
Invasive cervical cancer is thought to arise from the progression of precancerous lesions. How these lesions proceed from precancers to cancer remains unknown. Data regarding other tissues indicate that altered programmed cell death (apoptosis), in addition to cellular proliferation, is associated with the development of neoplasia. Therefore, in order to better understand the development of cervical neoplasia, we investigated the rate of apoptosis in cervical precancer and cancer. Archival cervical samples from normal epithelium (n = 11), low-grade squamous intraepithelial lesions (LSIL, n = 11), high-grade squamous intraepithelial lesions (HSIL, n = 10), and squamous cancers (n = 10) were evaluated for chromatin cleavage, a hallmark of programmed cell death. We used in situ end-labeling of DNA strand breaks by terminal deoxynucleotidyltransferase incorporation of biotinylated deoxyuridine to 3'-OH ends of DNA, identified by a nickel-avidin-peroxidase. The apoptotic index (sum of apoptotic bodies divided by the total nuclei times 100) significantly decreased (P < 0.001) as the degree of neoplasia increased: 3.5% (+/-0.4) in normal cervical epithelium (4.8 +/- 0.4) in LSIL, 1.4% (+/-0.4) in HSIL, and 0.4% (+/-0.1) in squamous cancers. Compared to normal epithelium, the total cell number per 10 mm2 increased significantly (P < 0.001): 124 (+/-12) in normal epithelium, 162 (+/-9.7) in LSIL, 315 (+/-31) in HSIL, and 413 (+/-32) in squamous cancers. We conclude that increasing cervical atypicality is associated with a decrease in apoptosis. We hypothesize from our data that one factor involved in the progression of neoplasia in the uterine cervix is a decrease in the rate of normal cellular deletion.
Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
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D017209:Apoptosis; D002452:Cell Count; D002584:Cervix Uteri / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D005260:Female; D006651:Histocytochemistry / Q000379:methods; D006801:Humans; D009361:Neoplasm Invasiveness; D018307:Neoplasms, Squamous Cell / Q000473:pathology; D011230:Precancerous Conditions / Q000473:pathology; D012016:Reference Values; D002583:Uterine Cervical Neoplasms / Q000473:pathology*