Consecutive Progression from Intratubular Germ Cell Neoplasm, Unclassified (IGCNU) to Seminoma and Ultimately to Embryonal Carcinoma of the Adult Testis: An Allelotyping Analysis of Cases with Embryonal Carcinoma Accompanied by Co-Existing Seminoma and/or IGCNU Components
Kosuke Miyai, Sohei Yamamoto, Keiichi Iwaya, Osamu Matsubara, Eugene J Mark. National Defense Medical College, Tokorozawa, Saitama, Japan; Massachusetts General Hospital and Harvard Medical School, Boston, MA
Background: The pathogenesis of embryonal carcinoma remains a matter of debate in adult testicular germ cell tumors (TGCTs). Some believe single consecutive progression from intratubular germ cell neoplasm, unclassified (IGCNU) to seminoma and embryonal carcinoma. Others believe that seminoma and embryonal carcinoma derive independently from IGCNU.
Design: From a cohort study of 18 patients with TGCT of embryonal carcinoma, a total of 25 co-existing histological components, consisting of 11 seminoma and 14 IGCNU components, were identified. We performed allelotyping analysis to clarify the genetic relationship between testicular embryonal carcinoma components and co-existing seminoma and/or IGCNU components. Their matched DNA was subjected to allelotyping analysis using 20 polymorphic markers located on 12 chromosome arms such as 3q, 5q, 6p, 9p, 10q, 11p, 12p, 12q, 13q, 17p, 17q and 18q.
Results: The concordance rate in the allelic pattern (loss of heterozygosity [LOH] or retention of heterozygosity) was 80% between embryonal carcinoma components and co-existing seminoma components, and 71% between embryonal carcinoma components and co-existing IGCNU components. Referring to Jacobs et al, the probability that IGCNU, seminoma, and embryonal carcinoma components in a specific case lose individuallty the same allele at a specific locus can be calculated as 1/2 x p1 x p2 x p3, where p1, p2, and p3 represent the frequencies of LOH at that locus in IGCNU, seminoma, and embryonal carcinoma components, respectively. It would be very unlikely that identical LOH pattern would be found both in embryonal carcinoma components and in co-existing seminoma or co-existing IGCNU components (probability < 0.05). Therefore, these findings indicated a clonal relationship among these components. Moreover, for all informative loci, the total frequency of LOH was 21% in IGCNU, 30% in seminoma, and 46% in embryonal carcinoma components (p< 0.05, respectively).
Conclusions: Our allelotyping analysis of cases with embryonal carcinoma accompanied with co-existing seminoma and/or IGCNU components suggests consecutive progression from IGCNU to seminoma and ultimately to embryonal carcinoma of the adult testis.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 138, Monday Afternoon