Elsevier

Gynecologic Oncology

Volume 63, Issue 1, October 1996, Pages 94-100
Gynecologic Oncology

Regular Article
Association between Cervical Neoplasia and Apoptosis as Detected byin SituNuclear Labeling

https://doi.org/10.1006/gyno.1996.0285Get rights and content

Abstract

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 usedin situend-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 mm2increased 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.

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To whom reprint requests should be addressed at Department of Obstetrics and Gynecology, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115. Fax: (617) 738-5124.

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