Allelotyping analysis suggesting a consecutive progression from intratubular germ cell neoplasia to seminoma and then to embryonal carcinoma of the adult testis.
Among adult testicular germ cell tumors, the pathogenesis of embryonal carcinoma remains a matter of debate. Some studies suggest a single consecutive progression from intratubular germ cell neoplasia, unclassified (IGCNU), to seminoma and then to embryonal carcinoma; others suggest that seminoma and embryonal carcinoma derive independently from IGCNU. This allelotyping study aimed to clarify the genetic relationship between embryonal carcinoma components and coexisting seminoma and/or IGCNU components. From a cohort of 18 patients with embryonal carcinoma, 11 coexisting seminoma components and 14 coexisting IGCNUs were identified. DNA isolated from each laser-microdissected tissue was subjected to polymerase chain reaction and loss of heterozygosity (LOH) analysis, using 20 polymorphic markers located on 12 chromosome arms (3q, 5q, 6p, 9p, 10q, 11p, 12p, 12q, 13q, 17p, 17q, and 18q). The concordance rate for allelic patterns was 82% between IGCNU and the coexisting seminoma components, 71% between IGCNU and the coexisting embryonal carcinoma components, and 80% between seminoma components and the coexisting embryonal carcinoma components. Estimation of probability indicated that these events were very unlikely to have occurred by chance. The total frequency of LOH increased progressively from IGCNU to seminoma and then to embryonal carcinoma, with statistically significant differences. In 7 cases with 3 histologic components, 28 chromosomal loci that showed LOH in the seminoma and embryonal carcinoma components were identified, and 15 (54%) retained heterozygosity in the coexisting IGCNUs. These findings suggest that a consecutive progression from IGCNU to seminoma, and ultimately, to embryonal carcinoma mainly occurred in the testicular germ cell tumor cases.
Department of Basic Pathology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan. Electronic address: dry2001@ndmc.ac.jp.
Kosuke
K
Miyai
Sohei
S
Yamamoto
Keiichi
K
Iwaya
Tomohiko
T
Asano
Seiichi
S
Tamai
Hitoshi
H
Tsuda
Osamu
O
Matsubara
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D018236:Carcinoma, Embryonal / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D005838:Genotype; D006801:Humans; D061346:Laser Capture Microdissection; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D018239:Seminoma / Q000235:genetics* / Q000473:pathology; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
Carcinogenesis; Embryonal carcinoma; Germ cell tumor; Loss of heterozygosity; Microdissection; Testis