Molecular genetic evidence supporting the neoplastic nature of fibrous stroma in testicular teratoma

Abstract

Testicular teratoma typically consists of heterogeneous mixtures of diverse epithelial and stromal components. The biological nature and genetic characteristics of the fibrous stroma of testicular teratomas have not been thoroughly investigated. Chromosome 12p abnormalities are the hallmark genetic alterations of germ cell tumors. We studied chromosome 12p abnormalities in the fibrous stroma and other components of pure testicular teratomas from 32 patients using interphase fluorescence in situ hybridization. Overall, 72% (23/32) of pure testicular teratomas had chromosome 12p abnormalities. Isochromosome 12p or 12p overrepresentation independent of isochromosome 12p was detected in the fibrous stroma in 53% (17/32) and 41% (13/32) of cases, respectively. Among the 17 cases positive for isochromosome 12p, 8 (47%) also had 12p overrepresentation. In 31% (10/32) cases, the fibrous stroma showed neither 12p overrepresentation nor isochromosome 12p. Isochromosome 12p and 12p overrepresentation were identified, respectively, in the gastrointestinal-type epithelium of 14/23 (61%) and 15/23 (65%) cases; in the respiratory-type epithelium of 41% (7/17) and 41% (7/17) cases; in the squamous epithelium of 62% (8/13) and 54% (7/13) cases; and in the cartilage of 63% (5/8) and 38% (3/8) cases. Concordant chromosomal 12p abnormalities were observed between the fibrous stroma and epithelial elements of testicular teratomas. Our results indicate that the fibrous stroma of testicular teratomas frequently has genetic abnormalities similar to those of the epithelial components. Concordant chromosome 12p alterations between the fibrous stroma and epithelial elements provide further evidence that both epithelial and fibrous components of teratoma are derived from a common progenitor.