HETEROGENEITY OF NUCLEAR-DNA PATTERN AND ITS RELATIONSHIP WITH CELL-CYCLE ACTIVITY PARAMETERS IN MULTINODULAR GOITER

OBJECTIVE Recent studies suggest that the malignancy rate in multinodu lar goitre is not significantly different from that observed in solita ry nodules anti that chromosomal aberrations are not infrequent in mul tinodular goitre, To further investigate this topic we determined the DNA pattern in multinodular goitres, DESIGN DNA ploidy and cell cycle activity parameters were determined in multinodular goitres, PATIENTS We evaluated 235 patients (185 female, 50 male, mean age 52 +/- 13 yea rs), who had undergone thyroidectomy; 11 of them harboured occult diff erentiated microcarcinoma, MEASUREMENTS DNA index(DI), coefficient of variation of G0/G1 phase (CV), percentage of cells in S phase (%S) and in G2+M phase (%G2-M) and proliferative index (PI = %S + %G2-M) were determined by flow cytometric analysis (FCM) in tissue samples taken f rom 3 different areas of the thyroid gland, RESULTS Aneuploid DNA was found in 50 goitres without carcinoma (22.3%) and in 5 goitres with ca rcinoma (45.5%), The mean PI of euploid cells in the goitre without ca rcinoma was significantly higher in the goitres with an aneuploid comp onent compared to the goitres without aneuploidy (10.8 +/- 1.3 SEM vs 6 +/- 0.32; P +/- 0.001). Also, the percentage difference between maxi mal and minimal PI found within each goitre (delta PI %) was higher in the former group (373 +/- 49 SEM vs 142 +/- 11.3; P < 0.0001). The PI was significantly higher in goitres with carcinoma compared to the go itres without carcinoma (12.9 +/- 3.2 SEM vs 7.07 +/- 0.40; P < 0.05). CONCLUSIONS The finding of increased proliferation rate in goitres wi th an aneuploid or neoplastic component suggests that some factors inv olved in goitrogenesis could also be responsible for the development o f chromosomal aberrations and/or for the selection of cellular clones endowed with high growth potential.