STEREOLOGICAL ESTIMATES OF NUCLEAR VOLUME IN SQUAMOUS-CELL CARCINOMA OF THE UTERINE CERVIX AND ITS PRECURSORS

Using modern stereology, this study was carried out to obtain base-line data concerning three-dimensional, mean nuclear size in precancerous and invasive lesions of the uterine cervix. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear upsilonBAR(v)) were obtained by point-sampling of nuclear intercepts in 51 pre-treatment biopsies from patients with invasive squamous cell carcinomas (SCC). Vertical sections from 27 specimens with cervical intraepithelial neoplasia (CIN) grades I through III were also investigated, along with 10 CIN III associated with microinvasion (CIN III + M). On average, nuclear upsilonBAR(v) was larger in SCC than in CIN III and CIN III + M together (2 P = 8.9.10(-5)). A conspicuous overlap of nuclear upsilonBAR(v) existed between all investigated lesional groups. The reproducibility of estimates of nuclear upsilon-BAR(v) in biopsies with SCC was acceptable (r = 0.85 and r = 0.84 in intra- and inter-observer studies, respectively). The efficiency of the sampling scheme was high, with more than 60% and more than 80% of the total observed variance contributed by differences between individual lesions with CIN and SCC, respectively. Estimates of nuclear upsilon-BAR(v) based on sampling within the whole epithelial thickness and on sampling in the lower one-third in CIN I and the lower two-thirds in CIN II lesions were of the same magnitude. Approximate estimates of the absolute variation of nuclear upsilon-BAR(v) were directly proportional to individual estimates of nuclear upsilon-BAR(v), whereas the relative variation of nuclear upsilon-BAR(v) tended to decrease with increasing mean nuclear volume. Based on the rather small number of cases investigated, estimates of nuclear upsilon-BAR(v) are unable to distinguish between different grades of CIN. However, the estimation of nuclear upsilon-BAR(v) is well-suited for the purposes of objective grading of malignancy in SCC.