Heterogeneity of nuclear DNA pattern and its relationship with cell cycle activity parameters in multinodular goitre.

Objective: Recent studies suggest that the malignancy rate in multinodular goitre is not significantly different from that observed in solitary nodules and that chromosomal aberrations are not infrequent in multinodular 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 years), who had undergone thyroidectomy; 11 of them harboured occult differentiated 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 from 3 different areas of the thyroid gland.

Results: Aneuploid DNA was found in 50 goitres without carcinoma (22.3%) and in 5 goitres with carcinoma (45.5%). The mean PI of euploid cells in the goitre without carcinoma was significantly higher in the goitres with an aneuploid component compared to the goitres without aneuploidy (10.8 +/- 1.3 SEM vs 6 +/- 0.32; P +/- 0.001). Also, the percentage difference between maximal 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 goitres without carcinoma (12.9 +/- 3.2 SEM vs 7.07 +/- 0.40; P < 0.05).

Conclusions: The findings of increased proliferation rate in goitres with an aneuploid or neoplastic component suggests that some factors involved in goitrogenesis could also be responsible for the development of chromosomal aberrations and/or for the selection of cellular clones endowed with high growth potential.