Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy

Autores
Chemes, Hector Edgardo; Venara, Marcela Cristina; del Rey, Graciela Monica; Arcari, A. J.; Musse, Mariana Paula; Papazian, R.; Forclaz, V.; Gottlieb, Silvia Elisa
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
All malignant testicular germ cell tumors (TGCT) of adult men are preceded by an in situ stage (CIS) of protracted evolution. Theadult CIS is well characterized, but there is debate on the phenotype of infantile CIS, its distinction from delayed maturation of germcells and prognostic potential. A large series of 43 patients with Disorders of Sex Development (DSD) and dysgenetic testes (90%ranging from neonates to 12 years, mean age 4.7 years), was studied by quantifying dysgenetic features, degree of germ cell abnormalities/atypia (GCA), expression of OCT 3/4 (a pluripotency-undifferentiation marker), germ cell ploidy and evolution to CIS andinvasive TGCT. Findings were compared with those of normal testes. The type of gonads present defined three groups of patients:bilateral testes (BT-DSD, n = 21), one testis and one streak gonad (CT-DSD, C for combined, n = 13), and ovarian-testicular combinations(OT-DSD, n = 9). There were 5 boys with infantile CIS, bilateral in 3 (total of 8 infantile CIS) and two patients with adult CIS,bilateral in one (total of 3 adult CIS). Two patients had bilateral seminomas one at 12?17 and the other at 23 years. Histological dysgenesiswas significantly higher in CT-DSD (p < 0.05), that had only 1 CIS. The highest frequency of GCA was in BT-DSD (p < 0.05),which coincided with a total of 11CIS + Seminomas. In all patients, aneuploidy was significantly higher (63%) than diploidy(p < 0.02), and GCA were more frequent in aneuploid than in diploid samples (p < 0.02). All CIS and TGCT were OCT 3/4 positive.Finally, there was a significant association between the triad Aneuploidy + GCA + OCT 3/4 positivity and the incidence of CIS (FisherExact test p < 0.002, relative risk 7.0). The degree of testicular dysgenesis (derived from abnormal organization of Sertoli cells in fetaltesticular cords) is inversely related to the incidence of CIS. Our data demonstrate that the combined use of OCT 3/4 expression,quantification of germ cell abnormalities-atypia and ploidy in dysgenetic testes can satisfactorily identify infantile CIS with high riskof malignant evolution and set it aside from delayed germ cell maturation with lower or nil neoplastic potential.
Fil: Chemes, Hector Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Venara, Marcela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: del Rey, Graciela Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Arcari, A. J.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutierrez"; Argentina
Fil: Musse, Mariana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Papazian, R.. Hospital Nacional “Prof. Dr. Alejandro Posadas”; Argentina
Fil: Forclaz, V.. Hospital Nacional “Prof. Dr. Alejandro Posadas”; Argentina
Fil: Gottlieb, Silvia Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Materia
Cis Markers
Disorders of Sex Development
Dsd
Oct 3/4
Ploidy
Prognostic Factors
Testicular Carcinoma in Situ (Cis)
Testicular Dysgenesis
Testicular Germ Cell Tumor (Tgct)
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/8187
Acceder
id CONICETDig_14dc8707c10b22eb4e9fa846dcce7b54
oai_identifier_str oai:ri.conicet.gov.ar:11336/8187
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancyChemes, Hector EdgardoVenara, Marcela Cristinadel Rey, Graciela MonicaArcari, A. J.Musse, Mariana PaulaPapazian, R.Forclaz, V.Gottlieb, Silvia ElisaCis MarkersDisorders of Sex DevelopmentDsdOct 3/4PloidyPrognostic FactorsTesticular Carcinoma in Situ (Cis)Testicular DysgenesisTesticular Germ Cell Tumor (Tgct)https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3All malignant testicular germ cell tumors (TGCT) of adult men are preceded by an in situ stage (CIS) of protracted evolution. Theadult CIS is well characterized, but there is debate on the phenotype of infantile CIS, its distinction from delayed maturation of germcells and prognostic potential. A large series of 43 patients with Disorders of Sex Development (DSD) and dysgenetic testes (90%ranging from neonates to 12 years, mean age 4.7 years), was studied by quantifying dysgenetic features, degree of germ cell abnormalities/atypia (GCA), expression of OCT 3/4 (a pluripotency-undifferentiation marker), germ cell ploidy and evolution to CIS andinvasive TGCT. Findings were compared with those of normal testes. The type of gonads present defined three groups of patients:bilateral testes (BT-DSD, n = 21), one testis and one streak gonad (CT-DSD, C for combined, n = 13), and ovarian-testicular combinations(OT-DSD, n = 9). There were 5 boys with infantile CIS, bilateral in 3 (total of 8 infantile CIS) and two patients with adult CIS,bilateral in one (total of 3 adult CIS). Two patients had bilateral seminomas one at 12?17 and the other at 23 years. Histological dysgenesiswas significantly higher in CT-DSD (p < 0.05), that had only 1 CIS. The highest frequency of GCA was in BT-DSD (p < 0.05),which coincided with a total of 11CIS + Seminomas. In all patients, aneuploidy was significantly higher (63%) than diploidy(p < 0.02), and GCA were more frequent in aneuploid than in diploid samples (p < 0.02). All CIS and TGCT were OCT 3/4 positive.Finally, there was a significant association between the triad Aneuploidy + GCA + OCT 3/4 positivity and the incidence of CIS (FisherExact test p < 0.002, relative risk 7.0). The degree of testicular dysgenesis (derived from abnormal organization of Sertoli cells in fetaltesticular cords) is inversely related to the incidence of CIS. Our data demonstrate that the combined use of OCT 3/4 expression,quantification of germ cell abnormalities-atypia and ploidy in dysgenetic testes can satisfactorily identify infantile CIS with high riskof malignant evolution and set it aside from delayed germ cell maturation with lower or nil neoplastic potential.Fil: Chemes, Hector Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Venara, Marcela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: del Rey, Graciela Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Arcari, A. J.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutierrez"; ArgentinaFil: Musse, Mariana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Papazian, R.. Hospital Nacional “Prof. Dr. Alejandro Posadas”; ArgentinaFil: Forclaz, V.. Hospital Nacional “Prof. Dr. Alejandro Posadas”; ArgentinaFil: Gottlieb, Silvia Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaWiley2014-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/8187Chemes, Hector Edgardo; Venara, Marcela Cristina; del Rey, Graciela Monica; Arcari, A. J.; Musse, Mariana Paula; et al.; Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy; Wiley; Andrology; 3; 1; 9-2014; 59-692047-2919enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/andr.301/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1111/andr.301info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:12:20Zoai:ri.conicet.gov.ar:11336/8187instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:12:21.078CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy
title Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy
spellingShingle Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy
Chemes, Hector Edgardo
Cis Markers
Disorders of Sex Development
Dsd
Oct 3/4
Ploidy
Prognostic Factors
Testicular Carcinoma in Situ (Cis)
Testicular Dysgenesis
Testicular Germ Cell Tumor (Tgct)
title_short Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy
title_full Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy
title_fullStr Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy
title_full_unstemmed Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy
title_sort Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy
dc.creator.none.fl_str_mv Chemes, Hector Edgardo
Venara, Marcela Cristina
del Rey, Graciela Monica
Arcari, A. J.
Musse, Mariana Paula
Papazian, R.
Forclaz, V.
Gottlieb, Silvia Elisa
author Chemes, Hector Edgardo
author_facet Chemes, Hector Edgardo
Venara, Marcela Cristina
del Rey, Graciela Monica
Arcari, A. J.
Musse, Mariana Paula
Papazian, R.
Forclaz, V.
Gottlieb, Silvia Elisa
author_role author
author2 Venara, Marcela Cristina
del Rey, Graciela Monica
Arcari, A. J.
Musse, Mariana Paula
Papazian, R.
Forclaz, V.
Gottlieb, Silvia Elisa
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cis Markers
Disorders of Sex Development
Dsd
Oct 3/4
Ploidy
Prognostic Factors
Testicular Carcinoma in Situ (Cis)
Testicular Dysgenesis
Testicular Germ Cell Tumor (Tgct)
topic Cis Markers
Disorders of Sex Development
Dsd
Oct 3/4
Ploidy
Prognostic Factors
Testicular Carcinoma in Situ (Cis)
Testicular Dysgenesis
Testicular Germ Cell Tumor (Tgct)
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv All malignant testicular germ cell tumors (TGCT) of adult men are preceded by an in situ stage (CIS) of protracted evolution. Theadult CIS is well characterized, but there is debate on the phenotype of infantile CIS, its distinction from delayed maturation of germcells and prognostic potential. A large series of 43 patients with Disorders of Sex Development (DSD) and dysgenetic testes (90%ranging from neonates to 12 years, mean age 4.7 years), was studied by quantifying dysgenetic features, degree of germ cell abnormalities/atypia (GCA), expression of OCT 3/4 (a pluripotency-undifferentiation marker), germ cell ploidy and evolution to CIS andinvasive TGCT. Findings were compared with those of normal testes. The type of gonads present defined three groups of patients:bilateral testes (BT-DSD, n = 21), one testis and one streak gonad (CT-DSD, C for combined, n = 13), and ovarian-testicular combinations(OT-DSD, n = 9). There were 5 boys with infantile CIS, bilateral in 3 (total of 8 infantile CIS) and two patients with adult CIS,bilateral in one (total of 3 adult CIS). Two patients had bilateral seminomas one at 12?17 and the other at 23 years. Histological dysgenesiswas significantly higher in CT-DSD (p < 0.05), that had only 1 CIS. The highest frequency of GCA was in BT-DSD (p < 0.05),which coincided with a total of 11CIS + Seminomas. In all patients, aneuploidy was significantly higher (63%) than diploidy(p < 0.02), and GCA were more frequent in aneuploid than in diploid samples (p < 0.02). All CIS and TGCT were OCT 3/4 positive.Finally, there was a significant association between the triad Aneuploidy + GCA + OCT 3/4 positivity and the incidence of CIS (FisherExact test p < 0.002, relative risk 7.0). The degree of testicular dysgenesis (derived from abnormal organization of Sertoli cells in fetaltesticular cords) is inversely related to the incidence of CIS. Our data demonstrate that the combined use of OCT 3/4 expression,quantification of germ cell abnormalities-atypia and ploidy in dysgenetic testes can satisfactorily identify infantile CIS with high riskof malignant evolution and set it aside from delayed germ cell maturation with lower or nil neoplastic potential.
Fil: Chemes, Hector Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Venara, Marcela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: del Rey, Graciela Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Arcari, A. J.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutierrez"; Argentina
Fil: Musse, Mariana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Papazian, R.. Hospital Nacional “Prof. Dr. Alejandro Posadas”; Argentina
Fil: Forclaz, V.. Hospital Nacional “Prof. Dr. Alejandro Posadas”; Argentina
Fil: Gottlieb, Silvia Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentina
description All malignant testicular germ cell tumors (TGCT) of adult men are preceded by an in situ stage (CIS) of protracted evolution. Theadult CIS is well characterized, but there is debate on the phenotype of infantile CIS, its distinction from delayed maturation of germcells and prognostic potential. A large series of 43 patients with Disorders of Sex Development (DSD) and dysgenetic testes (90%ranging from neonates to 12 years, mean age 4.7 years), was studied by quantifying dysgenetic features, degree of germ cell abnormalities/atypia (GCA), expression of OCT 3/4 (a pluripotency-undifferentiation marker), germ cell ploidy and evolution to CIS andinvasive TGCT. Findings were compared with those of normal testes. The type of gonads present defined three groups of patients:bilateral testes (BT-DSD, n = 21), one testis and one streak gonad (CT-DSD, C for combined, n = 13), and ovarian-testicular combinations(OT-DSD, n = 9). There were 5 boys with infantile CIS, bilateral in 3 (total of 8 infantile CIS) and two patients with adult CIS,bilateral in one (total of 3 adult CIS). Two patients had bilateral seminomas one at 12?17 and the other at 23 years. Histological dysgenesiswas significantly higher in CT-DSD (p < 0.05), that had only 1 CIS. The highest frequency of GCA was in BT-DSD (p < 0.05),which coincided with a total of 11CIS + Seminomas. In all patients, aneuploidy was significantly higher (63%) than diploidy(p < 0.02), and GCA were more frequent in aneuploid than in diploid samples (p < 0.02). All CIS and TGCT were OCT 3/4 positive.Finally, there was a significant association between the triad Aneuploidy + GCA + OCT 3/4 positivity and the incidence of CIS (FisherExact test p < 0.002, relative risk 7.0). The degree of testicular dysgenesis (derived from abnormal organization of Sertoli cells in fetaltesticular cords) is inversely related to the incidence of CIS. Our data demonstrate that the combined use of OCT 3/4 expression,quantification of germ cell abnormalities-atypia and ploidy in dysgenetic testes can satisfactorily identify infantile CIS with high riskof malignant evolution and set it aside from delayed germ cell maturation with lower or nil neoplastic potential.
publishDate 2014
dc.date.none.fl_str_mv 2014-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/8187
Chemes, Hector Edgardo; Venara, Marcela Cristina; del Rey, Graciela Monica; Arcari, A. J.; Musse, Mariana Paula; et al.; Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy; Wiley; Andrology; 3; 1; 9-2014; 59-69
2047-2919
url http://hdl.handle.net/11336/8187
identifier_str_mv Chemes, Hector Edgardo; Venara, Marcela Cristina; del Rey, Graciela Monica; Arcari, A. J.; Musse, Mariana Paula; et al.; Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy; Wiley; Andrology; 3; 1; 9-2014; 59-69
2047-2919
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/andr.301/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1111/andr.301
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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