Abstract Book - 26th ESPU Congress, Joint Meeting with ICCS + SPU + AAP/SOU + AAPU + SFU

175 / 492

09:05 - 09:10
S13-2 (LO)
★ PREDICTION OF GERM CELL CANCER OCCURRENCE IN POSTPUBERTAL
INDIVIDUALS WITH ANDROGEN INSENSITIVITY BASED ON PATHOLOGICAL
FINDINGS AND CANCER PREDISPOSITION SNPS
Katja P. WOLFFENBUTTEL1, Martine COOLS2, Jana KAPROVA3, Berenice MENDONCA4, Sten L.S. DROP5, Remko
HERSMUS6, Hans STOOP6, Ad J.M. GILLIS6, E COSTA7, S DOMENICE7, Lutz WÜNSCH8, Charmian A. QUIGLEY9, W.
ARLT10, Guy T'SJOEN11 and Leendert H.J. LOOIJENGA12
1) Erasmus Medical Center - Sophia Children's Hospital, Paediatric Urology, Rotterdam, NETHERLANDS - 2) Ghent
University and Ghent University Hospital, Department of Pediatrics, Ghent, BELGIUM - 3) Charles University and
University Hospital Motol, Prague, Department of Pediatrics, Prague, CZECH REPUBLIC - 4) Hospital das Clinicas,
Faculdade de Medicina, Universidade de Sao Paulo, Unidade de Endocrinologia do Desenvolvimento, Sao Paulo, BRAZIL -
5) Erasmus Medical Center Sophia Children's Hospital, Department of Pediatric Endocrinology, Rotterdam,
NETHERLANDS - 6) Erasmus Medical Center, Department of Pathology and Experimental Patho-Oncology, Rotterdam,
NETHERLANDS - 7) Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Unidade de
Endocrinologica, Sao Paulo, BRAZIL - 8) Universitätsklinikum Schleswig-Holstein and Universität zu Lübeck, Department
of Pediatric Surgery, Lübeck, GERMANY - 9) Indiana University, School of Medicine, Indianapolis, USA - 10) University of
Birmingham, Centre for Endocrinology, Diabetes and Metabolism, Birmingham, UNITED KINGDOM - 11) Ghent
University and Ghent University Hospital, Department of Endocrinology, Ghent, BELGIUM - 12) Erasmus Medical Center
and Josephine Nefkens Institute, Department of Pathology and Experimental Patho-Oncology, Rotterdam,
NETHERLANDS
PURPOSE
Gonadectomy is generally postponed until early adulthood in complete androgen insensitivity syndrome (CAIS) and
close surveillance of gonads in situ proposed in males with partial AIS (PAIS). Delaying gonadectomy further is
controversial given the lack of data regarding germ cell cancer (GCC) development in adulthood and the absence of
biomarkers for noninvasive GCC screening.
MATERIAL AND METHODS
Immunohistochemical study of 96 samples (CAIS: 72 gonadectomy, 7 biopsy; PAIS: 10 gonadectomy, 7 biopsy). All
surgical procedures were performed at or after the age of 14 years (median 17, range 14-54). All AIS cases were
genetically confirmed. We studied the prevalence of invasive GCC, carcinoma in situ (CIS), or signs of pre-malignancy
(combined aberrant OCT3/4 and KITLG expression) and assessed the correlation with a genetic predisposition for GCC
based on allele sequencing of 13 GCC-associated SNPs.
RESULTS
No invasive GCC were encountered. Changes suggestive for premalignancy were found in 8/79 (10.1%) CAIS samples
from five women (5/41; 12.2%) at a mean age of 16.6 (14-21) years; three women had bilateral changes. CIS was
detected in one girl with PAIS (1/10; 10%) gonadectomized at 15 years. Preliminary analysis reveals a significant
association between the occurrence of (pre)malignancy and a high genetic relative risk for GCC (p=0.003).
CONCLUSIONS
The prevalence of premalignant lesions in postpubertal CAIS women in this cohort was 12%. Lesions are already present
during adolescence and often bilateral. No prospective data exist regarding progression of such lesions to GCC. A
comparable prevalence was seen in PAIS, with possibly a higher risk of malignant progression given the residual AR
activity. Preliminary data suggest a significantly higher risk of (pre)malignancy in individuals with a genetic
predisposition for GCC.