title: Clonal origin of metastatic testicular teratomas.
abstract: OBJECTIVE
  Testicular teratomas in adult patients are histologically diverse tumors that frequently coexist with other germ cell tumor (GCT) components. These mixed GCTs often metastasize to retroperitoneal lymph nodes where multiple GCT elements are frequently present in the same metastatic lesion. Neither the genetic relationships among the different components in metastatic lesions nor the relationships between primary and metastatic GCT components have been elucidated.
  
  
  METHODS
  We examined metastases from 31 patients who underwent primary retroperitoneal lymph node dissection for metastatic testicular GCT. All patients had metastatic mature teratoma with one or more other GCT components. This study included a total of 72 metastatic GCT components and 16 primary GCT components from 31 patients. Genomic DNA samples from each component were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-assisted microdissection. Loss of heterozygosity (LOH) assays for seven microsatellite polymorphic markers on chromosomes 1p36 (D1S1646), 9p21 (D9S171 and IFNA), 9q21 (D9S303), 13q22-q31 (D13S317), 18q22 (D18S543), and 18q21 (D18S60) were done to assess clonality.
  
  
  RESULTS
  Twenty-nine of 31 (94%) cases showed allelic loss in one or more components of the metastatic GCTs. Twenty-nine of 31 mature teratomas showed allelic loss in at least one of seven microsatellite polymorphic markers analyzed. The frequency of allelic loss in informative cases of metastatic mature teratoma was 27% (8 of 30) with D1S1646, 34% (10 of 29) with D9S171, 37% (10 of 27) with IFNA, 27% (8 of 30) with D9S303, 46% (13 of 28) with D13S317, 26% (7 of 27) with D18S543, and 36% (10 of 28) with D18S60. Completely concordant allelic loss patterns between the mature teratoma and all of the other metastatic GCT components were seen in 26 of 29 cases in which the mature teratoma component showed LOH. Nearly identical allelic loss patterns were seen in the three remaining cases. In six cases analyzed, LOH patterns of each metastatic component were compared with each GCT component of the primary testicular tumor. In all six cases, each primary and metastatic component showed an identical pattern of allelic loss.
  
  
  CONCLUSIONS
  Our data support the common clonal origin of metastatic mature teratomas with other components of metastatic testicular GCTs and with each component of the primary tumor.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, and Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Jones
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Wang
authors.forename: Ming-Tse
authors.initials: MT
authors.lastname: Sung
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Ulbright
authors.forename: John N
authors.initials: JN
authors.lastname: Eble
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Beck
authors.forename: Richard S
authors.initials: RS
authors.lastname: Foster
authors.forename: John J
authors.initials: JJ
authors.lastname: Anagnostou
authors.forename: Clay
authors.initials: C
authors.lastname: Conner
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000293:Adolescent; D000328:Adult; D005787:Gene Frequency; D006801:Humans; D053685:Laser Therapy / Q000379:methods; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008297:Male; D042282:Microdissection / Q000379:methods; D018895:Microsatellite Repeats; D008875:Middle Aged; D013724:Teratoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*