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 ¯vv 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 ¯vv was larger in SCC than in CIN III and CIN III + M together (2P=8.9·10−5). A conspicuous overlap of nuclear ¯vv existed between all investigated lesional groups. The reproducibility of estimates of nuclear ¯vv in biopsies with SCC was acceptable (r=0.85 andr=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 ¯vv 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 ¯vv were directly proportional to individual estimates of nuclear ¯vv, whereas the relative variation of nuclear ¯vv tended to decrease with increasing mean nuclear volume. Based on the rather small number of cases investigated, estimates of nuclear ¯vv are unable to distinguish between different grades of CIN. However, the estimation of nuclear ¯vv is well-suited for the purposes of objective grading of malignancy in SCC.