Effect of hyperthermia 42.5 degrees C/120 min on 3H-thymidine incorporation in different tissue components of Wilms' tumors: an in vitro study.

BACKGROUND

Survival rates of Wilms' tumors are correlated to tumor histology. Clinical studies and histological investigations have shown that different histological tumor components of Wilms' tumors also reveal different sensitivities to cytostatic agents and ionizing radiation. The aim of this study is to examine the effect of hyperthermia to Wilms' tumors, generally, and to the different tumor tissues composing nephroblastomas.

METHODS

The 3H-thymidine labelling indices (LI) of 23 Wilms' tumors and one renal rhabdomyosarcoma were studied by an autoradiographic in vitro method at temperatures of 37.5 degrees C/120 min and 42.5 degrees C/120 min. The LI of each tumor was measured and likewise the LI of all histological tumor components defining standard risk and high risk. The effect of hyperthermia was calculated as the percentage of inhibition of 3H-thymidine incorporation.

RESULTS

Labelling indices between 22.4% and 46.3% (mean 33.2%) characterized Wilms' tumors as highly malignant and fast growing tumors. The LI of Wilms' tumors of standard risk and high risk did not differ significantly (33.8% vs. 30.4%). Also, epithelium and blastema of the same groups showed comparable high LI of 31.4% and 34.4%, respectively, and of 32.1% and 26.8%, respectively. The LI of stroma was significantly lower (11.9% and 10.9%). The mean LI of fetal-like rhabdomyoblastic cell elements of ten tumors was 24.5%. These tumor cells revealed a significantly higher LI than rhabdomyosarcomatous cells in one Wilms' tumor and one renal rhabdomyosarcoma (10.2% and 9.0%, respectively). The LI of anaplastic structures of one tumor was more than twice as high as the LI of surrounding tumor tissue. In vitro hyperthermia significantly inhibited 3H-thymidine incorporation into all nephroblastomas. Inhibition ranged between 13.7% and 84.6%, at an average of 47.3%. Four high risk tumors, as well as the single anaplastic and rhabdomyosarcomatous cells responded significantly stronger to heat than standard risk tumors (mean inhibition of 62.6% vs. 42.1%). Hyperthermia was more effective for blastema compared to epithelium and stroma. There was no correlation between the effect of hyperthermia and the amount of the 3H-thymidine LI at normothermia.

CONCLUSIONS

The tremendous inhibition of DNA synthesis by hyperthermia particularly in high risk tumors and highly malignant tumor components is of clinical interest for children with Wilms' tumors resistant to conventional therapy.