PMID- 23154771
OWN - NLM
STAT- MEDLINE
DCOM- 20130121
LR  - 20131121
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 36
IP  - 12
DP  - 2012 Dec
TI  - Molecular genetic evidence supporting the origin of somatic-type malignancy and 
      teratoma from the same progenitor cell.
PG  - 1849-56
LID - 10.1097/PAS.0b013e31826df1ab [doi]
AB  - Occasionally, testicular teratomas have been observed to occur in association 
      with somatic-type malignancies. The latter may be seen in the primary germ cell 
      tumor or, more commonly, in metastases after chemotherapy. The molecular-genetic 
      relationship between the teratoma and the somatic-type malignancy is uncertain. 
      We examined 27 pairs of teratoma and somatic-type malignancies in metastatic 
      lesions. Interphase fluorescence in situ hybridization (FISH) analysis for 12p 
      overexpression and i(12p) was performed on formalin-fixed, paraffin-embedded 
      specimens. In addition, we compared the pattern of allelic loss between the 
      teratoma and the somatic-type malignancy using 4 microsatellite DNA markers 
      (D1S508, interferon-alpha, D13S317, and D18S543). A laser capture microdissection 
      technique was used to procure separate tumor components. The somatic-type 
      malignancies included adenocarcinoma (13), primitive neuroectodermal tumor (5), 
      sarcoma not otherwise specified (5), squamous cell carcinoma (1), chondrosarcoma 
      (1), and rhabdomyosarcoma (2). Twenty-one of 27 tumor pairs (78%) showed a 
      similar pattern of overexpression of 12p and/or i(12p) in both components. Two of 
      the 27 (7%) tumor pairs showed i(12p) only in the teratomatous component, and 4 
      of the 27 (15%) tumor pairs showed no abnormalities of chromosome 12p by 
      interphase FISH. Eight of the 12 (67%) tumor pairs analyzed had identical 
      patterns of loss of heterozygosity in both the teratoma and the somatic-type 
      malignancy. Four of the 12 (33%) paired cases showed additional allelic loss at 
      the interferon-alpha locus in the somatic-type malignant component only. Our data 
      show that the somatic-type malignancies that develop in germ cell tumors have the 
      same genetic alterations, detectable by FISH and loss of heterozygosity studies, 
      as in the corresponding teratoma. These findings support that the somatic-type 
      malignancies within metastases and the teratomas are clonally related and likely 
      derived from a common progenitor cell. Interphase FISH can be performed on 
      formalin-fixed, paraffin-embedded tissue and is a sensitive method for detecting 
      12p overexpression and i(12p), thus aiding in establishing the germ cell origin 
      of somatic-type malignancies in this context.
FAU - Kum, Jennifer B
AU  - Kum JB
AD  - Department of Pathology and Laboratory Medicine, Indiana University School of 
      Medicine, Indianapolis, IN 46202, USA.
FAU - Ulbright, Thomas M
AU  - Ulbright TM
FAU - Williamson, Sean R
AU  - Williamson SR
FAU - Wang, Mingsheng
AU  - Wang M
FAU - Zhang, Shaobo
AU  - Zhang S
FAU - Foster, Richard S
AU  - Foster RS
FAU - Grignon, David J
AU  - Grignon DJ
FAU - Eble, John N
AU  - Eble JN
FAU - Beck, Stephen D W
AU  - Beck SD
FAU - Cheng, Liang
AU  - Cheng L
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Fixatives)
RN  - 1HG84L3525 (Formaldehyde)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cell Lineage/*genetics
MH  - *Chromosomes, Human, Pair 12
MH  - Clone Cells
MH  - Fixatives
MH  - Formaldehyde
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Laser Capture Microdissection
MH  - *Loss of Heterozygosity
MH  - Male
MH  - *Microsatellite Repeats
MH  - Middle Aged
MH  - Neoplasms, Complex and Mixed/*genetics/secondary
MH  - Neoplastic Stem Cells/*pathology
MH  - Paraffin Embedding
MH  - Teratoma/*genetics/secondary
MH  - Testicular Neoplasms/*genetics/pathology
MH  - Tissue Fixation
MH  - Young Adult
EDAT- 2012/11/17 06:00
MHDA- 2013/01/23 06:00
CRDT- 2012/11/17 06:00
PHST- 2012/11/17 06:00 [entrez]
PHST- 2012/11/17 06:00 [pubmed]
PHST- 2013/01/23 06:00 [medline]
AID - 00000478-201212000-00013 [pii]
AID - 10.1097/PAS.0b013e31826df1ab [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2012 Dec;36(12):1849-56. doi: 10.1097/PAS.0b013e31826df1ab.