Analysis of proliferative compartments in human tumors. II. Seminoma

Growth pattern and cell kinetics of 12 human seminomas were determined by means of vascular organ perfusion after orchiectomy. The arteria testicularis of the tumor-bearing testis was perfused up to 5 hours with dextran-diluted blood under normothermic and normotonic, simulated physiologic conditions. At defined periods, the specimen was exposed to tritiated and/or carbon 14-labeled thymidine. Autoradiograms prepared of whole tumor sections revealed a dependence of growth pattern on the stage of development. A homogeneous distribution of DNA synthesizing seminoma cells was found in small tumor foci. With increasing size, the zone of proliferation shifted to the periphery of the nodule giving rise to nodular subpopulations of high proliferative activity. In nodules of a diameter of more than about 2 cm the growth compartment consists of a highly proliferating invading cell layer at the edge of the tumor and intratumoral patches of proliferating cells near the vascular stroma. The largest part of the tumor remains at this stage in a quiescent state (G0). The mean labeling index of the seminoma cells was 11.6 +/- 1.4%, with the highest values found immediately adjacent to tumor vessels. High mitotic activity in an anaplastic seminoma was coupled with maximum labeling indices up to 41.9%. DNA synthesis time ts was 15.9 +/- 2.0 hours. The potential population doubling time for the proliferating fraction was in the range of 5 days. Lymphocytic infiltration reduced the proliferative activity in some parts, but was without effect in other areas of the seminoma. The seminoma is an example of a malignant human tumor with a rather regular growth pattern: The distribution of the proliferating compartment appears less dependent on cytologic or histologic structure, but more on tumor geometry and size.