Metastatic Teratomas with Secondary Malignant Components: Molecular Genetic Evidence That Somatic-Type Malignancies Arise from the Same Progenitor Cells as the Teratomatous Component.
Jennifer B Kum, Mingsheng Wang, Thomas M Ulbright, Stephen DW Beck, Richard S Foster, David J Grignon, John N Eble, Liang Cheng. Indiana University, Indianapolis
Background: Occasionally, testicular teratomas have been observed to develop secondary somatic-type malignant components. Such components may be seen in the primary germ cell tumor or, more commonly, within metastatic sites after chemotherapy with cisplatin-based agents. The molecular genetic relationship between teratoma and the secondary malignant component is uncertain.
Design: We examined 23 metastatic teratoma and secondary malignant component pairs of metastatic tumors. Interphase florescence in situ hybridization analysis for 12p overexpression and i(12p) were performed on formalin-fixed, paraffin-embedded specimens. Additionally, we compared the pattern of allelic loss between the teratoma and the secondary malignant component using four microsatellite DNA markers (D1S508; IFNA; D13S317 and D18S543). A laser capture microdissection technique was used to procure separate tumor components.
Results: The histologies of the secondary malignant components included adenocarcinoma (11), primitive neuroectodermal tumor (3), sarcoma (5), squamous cell carcinoma (1), chondrosarcoma (1) and rhabdomyosarcoma (2). Two of the 23 (8.7%) tumor pairs showed i(12p) in the teratomatous component only and 3 of the 23 (13%) tumor pairs showed no abnormalities of chromosome 12p by interphase FISH. Eighteen of 23 tumor pairs (78%) showed either overexpression of 12p and/or i(12p). Seven of the 8 (88%) tumor pairs tested, had identical patterns of loss of heterozygosity in both the teratoma and the secondary malignant component. One case showed allelic loss at the IFNA locus in the secondary malignant component only.
Conclusions: Our data show that the secondary malignant components which develop in germ cell tumors have the same genetic alterations detectable by florescence in situ hybridization and loss of heterozygosity studies as in the corresponding teratoma. These findings suggest that the somatic-type malignancies and the teratomas are clonally related and likely derived from a common progenitor cell. Interphase florescence in situ hybridization that can be performed on formalin-fixed, paraffin-embedded is a sensitive method for detecting 12p overexpression and i(12p), thus aid in establishing germ cell origin.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 83, Tuesday Afternoon