Methods: A total of 135 samples were analysed for DNA content. There were 85 cases of moderate or severe dysplasia: 40 cases (OED) did not progress to SCC (minimum follow-up of 5 years); 45 cases progressed to SCC (OED-SCC) within 6 to 193 months (mean 93.5). The 45 cases of SCC were also analysed as well as 5 samples of normal mucosa (NOM). Cell nuclei were extracted from 50 micron paraffin sections and Feulgen-stained cytospin monolayers were analysed using a DNA image cytometry system (Fairfield Imaging, Notts, UK). DNA Index (DI) was calculated relative to internal controls (DI=1.0) and all cases were also categorised as normal (diploid) or abnormal (aneuploid). The proportion of cells over 5c (5cER) was also calculated.
Results:
|
n |
Aneuploid |
Diploid |
DI (mean±SD) |
5cER (mean±SD) |
OED |
40 |
6 (15%) |
34 (85%) |
1.05±0.12 |
0.54±1.33 |
OED-SCC |
45 |
16 (36%) |
29 (64%) |
1.14±0.21 |
1.99±5.23 |
SCC |
45 |
22 (49%) |
23 (51%) |
1.11±0.17 |
2.19±4.73 |
16 of 45 OED-SCC were aneuploid compared to 6 of 40 OED (Fishers Exact: p = 0.03). A total of 22 of 85 dysplasias were aneuploid and 16 (73%) progressed to SCC. The DI and 5cER were significantly higher in OED-SCC compared to OED (Mann-Whitney: p = 0.02 and 0.02 respectively). The value of aneuploidy to predict progression was: sensitivity 0.36, specificity - 0.85, PPV 0.73, NPV 0.54. All the NOM samples were diploid with 5cER of 0.
Conclusions:. Dysplastic lesions with abnormal DNA content have an increased risk of malignant transformation. Ploidy analysis may assist in determining the prognosis of OED, but results must be used with caution, since the sensitivity is low (64% false negatives).
Supported by CONACYT Mexican studentship151236 to AT-R, and by Sheffield Hospitals Charitable Trust.