Identification of germ cells at risk for neoplastic transformation in gonadoblastoma
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Identification of germ cells at risk for neoplastic transformation in gonadoblastoma : an immunohistochemical study for OCT3/4 and TSPY. / Kersemaekers, Anne-Marie F; Honecker, Friedemann; Stoop, Hans; Cools, Martine; Molier, Michel; Wolffenbuttel, Katja; Bokemeyer, Carsten; Li, Yunmin; Lau, Yun-Fai Chris; Oosterhuis, J Wolter; Looijenga, Leendert H J.
in: HUM PATHOL, Jahrgang 36, Nr. 5, 05.2005, S. 512-21.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Identification of germ cells at risk for neoplastic transformation in gonadoblastoma
T2 - an immunohistochemical study for OCT3/4 and TSPY
AU - Kersemaekers, Anne-Marie F
AU - Honecker, Friedemann
AU - Stoop, Hans
AU - Cools, Martine
AU - Molier, Michel
AU - Wolffenbuttel, Katja
AU - Bokemeyer, Carsten
AU - Li, Yunmin
AU - Lau, Yun-Fai Chris
AU - Oosterhuis, J Wolter
AU - Looijenga, Leendert H J
PY - 2005/5
Y1 - 2005/5
N2 - Carcinoma in situ (CIS) is the precursor of malignant testicular germ cell tumors (GCTs) of adolescents and young adults, being the neoplastic counterpart of primordial germ cells/gonocytes. Carcinoma in situ cells will develop into invasive seminoma/nonseminoma. Gonadoblastoma (GB) is the precursor of invasive GCTs in dysgenetic gonads, predominantly dysgerminoma (DG). In this process, part of the Y chromosome (GBY region) is involved, for which TSPY is a candidate gene. A detailed immunohistochemical survey was performed for the known diagnostic markers, germ cell/placental alkaline phosphatase (PLAP), c-KIT, and OCT3/4, as well as testis-specific protein on the Y chromosome (TSPY) on a series of GBs, and adjacent invasive DGs. All 5 patients were XY individuals (4 females and 1 male). In contrast to c-KIT, PLAP was positive in all cases. The immature germ cells of GBs were positive for OCT3/4, whereas the mature germ cells were negative for this marker, but positive for TSPY. In every GB, a minor population of germ cells positive for both markers could be identified, similar to most CIS cells and early invasive DG. On progression to an invasive tumor, TSPY can be lost, a process that is also detectable in invasive testicular GCTs compared to CIS. These results indicate that GB is a heterogeneous mix of germ cells, in which the OCT3/4-positive cells have the potential to undergo progression to an invasive tumor. These early invasive stages are initially also positive for TSPY (like CIS), supporting a positive selection mechanism. Therefore, OCT3/4 in combination with TSPY is valuable to identify malignant germ cells in dysgenetic gonads. This could allow better prediction of the risk of progression to a GCT. In addition, the data support the model that GB represents the earliest accessible developmental stage of malignant GCTs.
AB - Carcinoma in situ (CIS) is the precursor of malignant testicular germ cell tumors (GCTs) of adolescents and young adults, being the neoplastic counterpart of primordial germ cells/gonocytes. Carcinoma in situ cells will develop into invasive seminoma/nonseminoma. Gonadoblastoma (GB) is the precursor of invasive GCTs in dysgenetic gonads, predominantly dysgerminoma (DG). In this process, part of the Y chromosome (GBY region) is involved, for which TSPY is a candidate gene. A detailed immunohistochemical survey was performed for the known diagnostic markers, germ cell/placental alkaline phosphatase (PLAP), c-KIT, and OCT3/4, as well as testis-specific protein on the Y chromosome (TSPY) on a series of GBs, and adjacent invasive DGs. All 5 patients were XY individuals (4 females and 1 male). In contrast to c-KIT, PLAP was positive in all cases. The immature germ cells of GBs were positive for OCT3/4, whereas the mature germ cells were negative for this marker, but positive for TSPY. In every GB, a minor population of germ cells positive for both markers could be identified, similar to most CIS cells and early invasive DG. On progression to an invasive tumor, TSPY can be lost, a process that is also detectable in invasive testicular GCTs compared to CIS. These results indicate that GB is a heterogeneous mix of germ cells, in which the OCT3/4-positive cells have the potential to undergo progression to an invasive tumor. These early invasive stages are initially also positive for TSPY (like CIS), supporting a positive selection mechanism. Therefore, OCT3/4 in combination with TSPY is valuable to identify malignant germ cells in dysgenetic gonads. This could allow better prediction of the risk of progression to a GCT. In addition, the data support the model that GB represents the earliest accessible developmental stage of malignant GCTs.
KW - Adolescent
KW - Adult
KW - Alkaline Phosphatase
KW - Cell Cycle Proteins
KW - Cell Transformation, Neoplastic
KW - DNA-Binding Proteins
KW - Dysgerminoma
KW - Female
KW - GPI-Linked Proteins
KW - Germ Cells
KW - Gonadoblastoma
KW - Humans
KW - Immunohistochemistry
KW - In Situ Hybridization, Fluorescence
KW - Isoenzymes
KW - Male
KW - Nuclear Proteins
KW - Ovarian Neoplasms
KW - Proto-Oncogene Proteins c-kit
KW - Seminoma
KW - Sex-Determining Region Y Protein
KW - Testicular Neoplasms
KW - Transcription Factors
KW - Tumor Markers, Biological
U2 - 10.1016/j.humpath.2005.02.016
DO - 10.1016/j.humpath.2005.02.016
M3 - SCORING: Journal article
C2 - 15948118
VL - 36
SP - 512
EP - 521
JO - HUM PATHOL
JF - HUM PATHOL
SN - 0046-8177
IS - 5
ER -