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

Autor: Marcela Venara, V. Forclaz, Mariana P. Musse, Héctor E. Chemes, R. Papazian, G. del Rey, Silvia Gottlieb, Andrea Arcari
Rok vydání: 2015
Předmět:
Male
Endocrinology
Diabetes and Metabolism
DSD
Aneuploidy
Medicina Clínica
Gonadal Dysgenesis
TESTICULAR GERM CELL TUMOR (TGCT)
Endocrinology
Risk Factors
CIS MARKERS
Atypia
DISORDERS OF SEX DEVELOPMENT
Child
Fisher's exact test
Incidence
Sexual Development
Sertoli cell
OCT 3/4
Seminoma
Phenotype
medicine.anatomical_structure
Child
Preschool
symbols
Female
Carcinoma in Situ
Germ cell
medicine.medical_specialty
CIENCIAS MÉDICAS Y DE LA SALUD
Gonad
Adolescent
Urology
Argentina
Biology
Risk Assessment
Young Adult
symbols.namesake
Dysgenesis
Testicular Neoplasms
Predictive Value of Tests
Internal medicine
Biomarkers
Tumor
PROGNOSTIC FACTORS
medicine
Humans
TESTICULAR DYSGENESIS
Genetic Predisposition to Disease
Genetic Testing
PLOIDY
TESTICULAR CARCINOMA IN SITU (CIS)
Retrospective Studies
Fetus
Ploidies
Infant
Newborn
Infant
medicine.disease
Reproductive Medicine
Andrología
Octamer Transcription Factor-3
Zdroj: Andrology. 3:59-69
ISSN: 2047-2919
Popis: 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
Databáze: OpenAIRE
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