Gender dimorphism and age of onset in malignant peripheral nerve sheath tumor preclinical models and human patients.
BACKGROUND
Gender-based differences in disease onset in murine models of malignant peripheral nerve sheath tumor (MPNST) and in patients with Neurofibromatosis type-1-(NF-1)-associated or spontaneous MPNST has not been well studied.


METHODS
Forty-three mGFAP-Cre+;Ptenloxp/+;LSL-K-rasG12D/+ mice were observed for tumor development and evaluated for gender disparity in age of MPNST onset. Patient data from the prospectively collected UCLA sarcoma database (1974-2011, n = 113 MPNST patients) and 39 published studies on MPNST patients (n = 916) were analyzed for age of onset differences between sexes and between NF-1 and spontaneous MPNST patients.


RESULTS
Our murine model showed gender-based differences in MPNST onset, with males developing MPNST significantly earlier than females (142 vs. 162 days, p = 0.015). In the UCLA patient population, males also developed MPNST earlier than females (median age 35 vs. 39.5 years, p = 0.048). Patients with NF-1-associated MPNST had significantly earlier age of onset compared to spontaneous MPNST (median age 33 vs. 39 years, p = 0.007). However, expanded analysis of 916 published MPNST cases revealed no significant age difference in MPNST onset between males and females. Similar to the UCLA dataset, patients with NF-1 developed MPNST at a significantly younger age than spontaneous MPNST patients (p < 0.0001, median age 28 vs. 41 years) and this disparity was maintained across North American, European, and Asian populations.


CONCLUSIONS
Although our preclinical model and single-institution patient cohort show gender dimorphism in MPNST onset, no significant gender disparity was detected in the larger MPNST patient meta-dataset. NF-1 patients develop MPNST 13 years earlier than patients with spontaneous MPNST, with little geographical variance.
Elizabeth
E
Shurell
Linh M
LM
Tran
Jonathan
J
Nakashima
Kathleen B
KB
Smith
Brenna M
BM
Tam
Yunfeng
Y
Li
Sarah M
SM
Dry
Noah
N
Federman
William D
WD
Tap
Department of Surgery, University of California - Los Angeles, Division of Surgical Oncology, 10833 Le Conte Ave, Room 54-140 CHS, 90095-1782 Los Angeles, California. hwu@mednet.ucla.edu.
Hong
H
Wu
Fritz C
FC
Eilber
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005818:Genetic Engineering; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D018317:Nerve Sheath Neoplasms / Q000453:epidemiology* / Q000235:genetics; D009456:Neurofibromatosis 1 / Q000453:epidemiology*; D010524:Peripheral Nervous System Neoplasms / Q000453:epidemiology* / Q000235:genetics; D012727:Sex Characteristics; D012737:Sex Factors; D055815:Young Adult