Identical allelic losses in mature teratoma and other histologic components of malignant mixed germ cell tumors of the testis

Abstract

Teratomas of the testis in post-pubertal patients are histologically diverse tumors that often coexist with other types of germ cell tumors. Using laser capture microdissection and loss of heterozygosity analysis, we investigated the clonality of mature teratoma and its relationship to other components of malignant mixed germ cell tumors to gain potential insight into the histogenetic relationship of teratoma with other germ cell tumor components. All 16 patients had mature teratoma as one component of their mixed germ cell tumors. The other histological subtypes included immature teratoma, seminoma, embryonal carcinoma, yolk sac tumor, and choriocarcinoma. Laser-assisted microdissection was performed on the formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction was used to amplify genomic DNA at specific loci on chromosome 1p36.2 (D1S508), 2q22-32 (D2S156), 9p21-22 (D9S162), 11p13 (D11S903), 12q22-23 (D12S1051), and 18q21 (D18S46). Fourteen of 16 (88%) cases showed allelic loss in one or more components of the mixed germ cell tumors. Fourteen of 16 mature teratomas showed allelic loss in at least one of six microsatellite polymorphic markers analyzed. The frequency of allelic loss in mature teratoma was 50% (7 of 14) with D1S508, 33% (5 of 15) with D2S156, 58% (7 of 12) with D9S162, 43% (6 of 14) with D11S903, 20% (3 of 15) with D12S1051, and 33% (5 of 15) with D18S46. Completely concordant allelic loss patterns between mature teratoma and all of the other germ cell tumor components were seen in 10 of 14 tumors in which mature teratoma showed loss of heterozygosity. Our data support the common clonal origin of mature teratoma with other components of malignant mixed germ cell tumors of the testis.

Figure 1.

Laser micordissection of tumor from patients with malignant mixed germ cell tumor of the testis. Hematoxylin-eosin-stained sections showed mature teratoma (A), immature teratoma (D), embroynla carcinoma (G), yolk sac tumor (J), choriocarcinoma (M), and seminoma (P) before laser microdissection. Panels B, E, H, K, N, G, showed corresponding tumors after microdissection. Panels C, F, I, L, O, and R showed micordissected tissues ready for DNA analysis.

Figure 2.

Representative results of loss of heterozygosity analysis. DNA was prepared from normal tissue and different components of malignant mixed germ cell tumor, amplified by polymerase chain reaction using polymorphic markers D1S508, D2S156, D9S162, D11S903, D12S1051, and D18D46, and separated by gel electrophoresis. Arrows, allelic bands; N, normal tissue (control); MT, mature teratoma; IMT, immature teratoma; EC, embryonal carcinoma; YST, yolk sac tumor; CC choriocarcinoma, SE, seminoma.